Abstract
Background
Depression is a relatively common experience in older adults. The syndrome is associated with considerable distress, morbidity and service commitment. Approximately two thirds of patients presenting with severe forms will respond to antidepressant treatment and the last twenty years has witnessed a great increase in the number of these drugs. Older, frail people are particularly vulnerable to side effects.
Objectives
The aims of this review were to examine the efficacy of antidepressant classes, to compare the withdrawal rates associated with each class and describe the side effect profile of antidepressant drugs for treating depression in patients described as elderly, geriatric, senile or older adults, aged 55 or over.
Search methods
The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR‐Studies) was searched (2003‐08‐13). Reference lists of relevant papers and previous systematic reviews were hand searched for published reports and citations of unpublished studies.
Selection criteria
Only randomised controlled trials were included. Trials had to compare at least two active antidepressant drugs in the treatment of depression.
Data collection and analysis
Reviewers extracted data independently. In examining efficacy, the reviewers assumed that people who died or dropped out had no improvement. Withdrawal rates irrespective of cause and specifically due to side effects were compared between drug classes. Relative risk (RR) for dichotomous data and weighted mean difference for continuous data were calculated with 95% confidence intervals (CI). Qualitative side effect data were reported in terms of ratios of side effects and percentage of patients experiencing specific side effects.
Main results
A total of 32 trials provided data for inclusion in the review in terms of efficacy, withdrawal and side effect analysis. We were unable to find any differences in efficacy when comparing classes of antidepressants. Tricyclic antidepressants (TCAs) compared less favourably with selective serotonin reuptake inhibitors (SSRIs) in terms of numbers of patients withdrawn irrespective of reason (RR: 1.23, CI 1.05 to 1.43) and number withdrawn due to side effects (RR: 1.36, CI 1.09 to 1.70). Further analyses demonstrated that TCA related antidepressants had similar withdrawal rates to SSRIs irrespective of reason of withdrawal (RR: 1.49, CI 0.74 to 2.98) or withdrawal due to side effects (RR: 1.07, CI 0.43 to 2.70). The qualitative analysis of side effects showed a small increased profile of gastro‐intestinal and neuropsychiatric side effects associated with classical TCAs.
Authors' conclusions
Our findings suggest that SSRIs and TCAs are of the same efficacy. However, we have found some evidence suggesting that TCA related antidepressants and classical TCAs have different side effect profiles and are associated with differing withdrawal rates when compared with SSRIs. The review suggests that classical TCAs are associated with a higher withdrawal rate due to side effect experience, although these results must be interpreted with caution due to the heterogeneity of the drugs and patient populations.
Plain language summary
Antidepressants for depressed older people
This review compared the efficacy, withdrawal rates and side effects of different antidepressant classes in the treatment of depression in older people. Thirty‐two studies provided data for the review. Our main findings indicate that tricyclic antidepressants (classical and tricyclic related) and selective serotonin reuptake inhibitors (SSRIs) are equally efficacious. However, when comparing the two tricyclic groups with SSRIs we found that tricyclic related antidepressants were similar to SSRIs in terms of overall withdrawal rate, and classical tricyclic antidepressants were associated with a higher withdrawal rate due to side effects. These findings are reflected in the differing side effect profiles when comparing both tricyclic groups with SSRIs. The findings of the review must be interpreted with some caution in view of the relatively low patient numbers and lack of side effect data.
Background
The presence of depression in the community ranges from 10‐15%. This includes both major and minor depression (Katona 1994). The prevalence of major depression in people over the age of sixty is between two and five percent. It is considerably higher in older people with physical illness (Murphy 1982). Approximately 50‐60% of patients are thought to improve clinically as a consequence of antidepressant treatment (Schneider 1995). These findings are supported by a systematic review of antidepressant versus placebo in the treatment of depression in this age group (Wilson 2005).
It is generally acknowledged that older, frail depressed patients are particularly prone to side effects of antidepressants (Katona 1994). The effects of multiple drug prescribing often encountered in this population may well compound these. Older patients are more prone to the cardio‐vascular side effects of antidepressants (Woodhouse 1992). The anticholinergic side effects of many of these antidepressants are likely to promote cognitive dysfunction (Moskowitz 1986). Such side effects are likely to affect compliance, treatment outcome and the effectiveness of both short and long term treatment.
Antidepressants are drugs that are effective in the treatment of depression (usually moderate or severe). The last decade has witnessed the development of a wide range of antidepressants with differing pharmacological characteristics, with varying side effect profiles. Antidepressants may be grouped in accordance with the classification provided by the British National Formulary (BNF) (BMA 1999). Tricyclic antidepressants (TCAs) refer to those antidepressants that are characterised by a three‐ring structure (classical TCAs), and to those antidepressants with one, two and four rings with broadly similar properties (TCA ‐related antidepressants). The selective serotonin reuptake inhibitors class (SSRIs) refers to a group of drugs that selectively inhibit the re‐uptake of serotonin, a chemical of recognised importance in the biochemical causes of depression. Likewise, the mono‐amine oxidase inhibitors (MAOIs) refer to a class of drugs designed to inhibit monoamine oxidase, which in turn results in accumulation of amine neurotransmitters. Lastly, the newer antidepressants that do not readily fall within these pharmacological classes may be grouped as 'atypical' antidepressants.
This review examines randomised controlled trials of antidepressants in people aged 55 and over, or classified as 'elderly'. In undertaking this review we completed the search for all trials of antidepressants in this age group, identified those trials that generated data regarding efficacy, rates of withdrawal and side effects. Antidepressants were grouped in accordance with the classifications provided by the BNF described above, maintaining consistency with a related Cochrane review examining the relative efficacy of antidepressants compared to placebo in this age group (Wilson 2005). We aimed to compare the comparative efficacy of differing drug classes and the withdrawal rates in trials of antidepressants, and to describe the side effects experienced by patients taking these drugs.
Objectives
To examine the comparative efficacy of different antidepressant classes in the treatment of depression in older people. To test the hypothesis that different groups of antidepressants are similar in terms of withdrawal rates, irrespective of cause and due to drug related side effects. To compare the profile of side effects experienced by older people taking different classes of antidepressants.
Methods
Criteria for considering studies for this review
Types of studies
The review included all randomised controlled trials that compared two or more antidepressants in the treatment of depression in subjects over the age of 55 or described as elderly, senile, geriatric or older adults. Dosage finding trials were excluded.
Types of participants
Patients of both sexes were included in the review if diagnosed as suffering from depression by any criteria. This included patients suffering from major depression, dysthymia, unipolar depression and non‐specified depression. The review included patients over the age of 55 or described as elderly, senile, geriatric or older adults. Patients suffering from concomitant physical illness were included in the review.
Trials including patients under the age of 55 (or those not described as elderly, senile, geriatric or older adult) were excluded unless data concerning those patients were randomised and analysed separately. Patients suffering from other mental disorders (including both bipolar affective disorder and dementia) were excluded from the review.
Types of interventions
The review included all drugs described by the author as antidepressant drug treatments. Trials that used psychotherapy or psychosocial interventions in combination with all antidepressant treatments were also included.
Antidepressants were grouped by class of drug as defined by British National Formulary (BMA 1999). When not classified by the BNF, drugs were allocated to the pharmacological class to which they were most similar. The principal classes of drugs identified were: 1. Tricyclic antidepressants (TCAs) a) Classical tricyclics (classical TCAs): doxepin, amitriptyline, imipramine, clomipramine, dothiepin, nortriptyline, trimipramine, desipramine, nomifensine b) Tricyclic related (TCA related): mianserin, trazodone, maprotiline, viloxazine 2. Selective serotonin reuptake inhibitors (SSRIs): paroxetine, fluoxetine, citalopram, fluvoxamine, sertraline 3. Monoamine oxidase inhibitors (MAOIs): phenelzine, moclobemide 4. Atypical antidepressants: buspirone, bupropion, milnacipan, venlafaxine, reboxetine (the heterogeneity of drugs included within the atypical antidepressant class limits the relevance of combining these drugs as one class of antidepressants, however the review authors wished to determine whether these newer antidepressants were less likely to be associated with efficacy and withdrawal when compared with more established TCAs.
Trials that randomised psychotherapy against an antidepressant were excluded, as were trials that randomised to more than one antidepressant simultaneously.
The comparisons planned to be conducted by this review (if trials were available) were: 1. TCAs versus SSRIs 2. TCAs versus MAOIs 3. TCAs versus atypicals 4. SSRIs vrsus MAOIs 5. SSRIs versus atypicals 6. MAOIs versus atypicals
Types of outcome measures
Primary outcome The primary outcome was efficacy, measured firstly as recovery rates (recovery versus failure to recover) between drug classes. In undertaking the efficacy analysis it was assumed that patients who dropped out or died during the trial demonstrated no improvement. Efficacy was also measured as a continuous outcome, using rating scales such as the Hamilton Depression Rating Scale (Hamilton 1967).
Secondary outcome The secondary outcome was withdrawal rates, which referred to the number of patients withdrawn from antidepressant class groups irrespective of the cause, and the total number of patients withdrawn from receiving antidepressant treatment as a consequence of experiencing side effects.
Tertiary outcome Tertiary outcomes included comparisons of side effects experienced by patients receiving antidepressants. These data were expressed qualitatively in terms of the percentage of different side effects experienced by patients and the ratio of side effects experienced by patients receiving each class of antidepressant, enabling comparison between differing drug classes. Data were presented by organ system as determined by symptomatic expression. Patients who died or were withdrawn were included in the side effect analysis.
Search methods for identification of studies
See Collaborative Review Group search strategy The two‐stage search strategy devised by CCDAN was employed. The first stage involved the employment of the review group search strategy to identify all antidepressant trials. The second stage involved the employment of validated MESH terms to identify trials that include older people (Wilson 2005). Reference lists of relevant papers and previous systematic reviews were hand searched for published reports and citations of unpublished studies. The searches were conducted with the assistance of an information specialist.
Electronic bibliographic databases The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR‐Studies) was searched (2003‐08‐13) using the search terms. Diagnosis = Depressi* or Dysthymi* and Intervention = Antidepressive Agents or "Monoamine Oxidase Inhibitors" or "Selective Serotonin Reuptake Inhibitors" or "Tricyclic Drugs" or Acetylcarnitine or Alaproclate or Amersergide or Amiflamine or Amineptine or Amitriptyline or Amoxapine or Befloxatone or Benactyzine or Brofaromine or Bupropion or Butriptyline or Caroxazone or Chlorpoxiten or Cilosamine or Cimoxatone or Citalopram or Clomipramine or Clorgyline or Clorimipramine or Clovoxamine or Deanol or Demexiptiline or Deprenyl or Desipramine or Dibenzipin or Diclofensine or Dothiepin or Doxepin or Duloxetine or Etoperidone or Femoxetine or Fluotracen or Fluoxetine or Fluparoxan or Fluvoxamine or Idazoxan or Imipramine or Iprindole or Iproniazid or isocarboxazid or Litoxetine or Lofepramine or Maprotiline or Medifoxamine or Melitracen or Metapramine or Mianserin or Milnacipran or Minaprine or Mirtazapine or Moclobemide or Nefazodone or Nialamide or Nomifensine or Nortriptyline or Noxiptiline or Opipramol or Oxaflozane or Oxaprotiline or Pargyline or Paroxetine or Phenelzine or Piribedil or Pirlindole or Pivagabine or Prosulpride or Protriptyline or Quinupramine or Reboxetine or Rolipram or Sertraline or Setiptiline or Teniloxine or Tetrindole or Thiazesim or Thozalinone or Tianeptine or Toloxatone or Tomoxetine or Tranylcypromine or Trazodone or Trimipramine or Venlafaxine or Viloxazine or Viqualine or Zimeldine and Age Group = Aged
Handsearches Reference lists of relevant papers and previous systematic reviews were hand searched for published reports and citations of unpublished studies.
Data collection and analysis
Selection of studies Two reviewers independently assessed the relevance of each abstract and classified them as: 1. eligible 2. unclear eligibility 3. not eligible Those falling into either category 1 or 2 had the full article retrieved. These were then assessed by two reviewers, blind to the decision made by each other, against preset criteria and rated on a scoring sheet. In cases of disagreement a decision was reached by open discussion and consensus. Reasons for exclusion and/or inclusion were recorded.
Quality assessment All trials included in the review were classified according to the quality assessment criteria set out in the Cochrane Reviewers' Handbook (Alderson 2004). Studies were rated as A (adequate allocation concealment), B (unclear) or C (inadequate allocation concealment). The 23‐item quality assessment instrument developed by Montcrieff 2001 was also used to assess the methodological quality of studies. The Montcrieff 2001 scale rates trials 0, 1 or 2 on the reporting of /conducting of the trial, with the higher score showing a higher quality study. Items include information provided on randomisation, blindness of researchers and subjects, allocation concealment, description of sample, power analysis report etc. The total score of these items enables each trial to compared in terms of the quality of studies.
Data extraction Data were extracted from each study, using a pre‐designed form by two reviewers, differences were resolved following discussion and re‐examination of the study. Studies were categorised into three groups: trials that generated efficacy data, trials that provided data concerning side effects and trials that generated data regarding withdrawals.
Statistical Analysis
Pooling of data Efficacy analysis: For dichotomous data, relative risk (RR) together with 95% confidence intervals were used to provide a pooled estimate for studies, using a random effects model. Continuous data were pooled by calculating the weighted mean difference where studies used the same instruments and standardised mean differences where different scales were used to measure the same outcome.
Withdrawal rates: Overall withdrawal rates (withdrawal irrespective of cause) were examined using relative risk (RR) and 95% confidence intervals to provide a pooled estimate, which was calculated using a random effects model. A second analysis was undertaken examining withdrawal due to side effects, using the same techniques.
Side effects: Side effect data for each drug class were presented by organ system in the form of side effect: patient ratio to enable comparison between classes. Data regarding side effect profile were extracted from all available studies and reported qualitatively. Individual side effect symptom and signs were listed. Where terms describing individual side effects were similar, they were combined. All side effect categories were grouped by organ system. Systems included: Neuropsychiatric, Gastrointestinal, Respiratory, Sensory, Genitourinary, Dermatological and Cardiovascular. Assessment of heterogeneity We anticipated that other variables associated with ageing (such as physical ill health) were likely to influence the efficacy, withdrawal rates and expression of side effects as a consequence of antidepressant medication. Where possible the influence of patient characteristics, for example, inpatients, outpatients and community samples, subtypes of depression, physical illness, people under the age of 75 versus patients over the age of 75 were studied. As numbers of patients withdrawn due to side effects has been shown to be dependent on the frequency of assessments (Williams 2000), this issue was examined in the context of the trials included in the review. In addition, a formal test for statistical heterogeneity, the natural approximate chi‐squared test, was conducted.
Subgroup analyses Antidepressant drugs were categorised by group as determined by the British National Formulary. This has the potential of generating the following groups of antidepressants; trycyclic antidepressants, trycyclic related antidepressants, monoamine oxidase inhibitors (and reversible monoamine oxidase inhibitors, selective serotonin re‐uptake inhibitors and 'other' or atypical antidepressants. In this review, we compared all tricyclic antidepressants (classical and related) with SSRIs and then explored the subcategories as defined by the British National Formulary as follows: 1. classical TCAs versus SSRIs 2. related TCAs versus SSRIs 3. classical TCAs versus MAOIs 4. related TCAs versus MAOIS 5. classical TCAs versus atypicals 6. related TCAs versus atypicals
Our intention is to compare the efficacy, withdrawal rates and side effect profiles of these groups.
Other planned subgroup analyses: Setting (inpatient/outpatient/community) Subtypes of depression Comorbid physical illness Age (under 75 vs 75 and over)
Sensitivity analysis As a test of robustness of our results, sensitivity analysis was conducted by two reviewers to assess the effects of excluding lower methodological quality studies, using the quality assessment instrument developed by Montcrieff 2001.
Publication bias A funnel plot was used to assess publication bias.
Results
Description of studies
A total of 163 studies were identified by the search strategy. Of these, 32 had usable data, and were included in the review as given below. The 119 studies excluded from the review are presented in the table of Characteristics of excluded studies, with reasons for exclusion. The remaining 12 studies are awaiting assessment. Included trials were classified into those that provided data regarding efficacy, withdrawal rates and side effects.
Included studies Seventeen studies contributed data towards the efficacy analysis (Bocksberger 1993; De Ronchi 1998; Dorman 1991; De Ronchi 1998; Georgotas 1986; Geretsegger 1995; Halikas 1995; Hoyberg 1996; Hutchinson 1991; Kyle 1998; Mahapatra 1997; Mulsant 1998; Nair 1995; Navarro 2001; Pelicier 1993; Smeraldi 1998; Tignol 1998).
Twenty‐six studies provided sufficient data to enable analysis of withdrawal rates (Bocksberger 1993; Brion 1996; De Ronchi 1998; Dorman 1991; Dunningham 1994; Falk 1989; Feighner 1985; Georgotas 1986; Geretsegger 1995; Guillibert 1989; Halikas 1995; Hoyberg 1996; Hutchinson 1991; Katona 1999; Kyle 1998; La Pia 1992; Mahapatra 1997; Mulsant 1998; Nair 1995; Navarro 2001; Pelicier 1993; Phanjoo 1991; Rahman 1991; Schweizer 1998; Smeraldi 1998; Tignol 1998)
Twenty studies provided data of sufficient quality to be included in the side effect analysis (Ather 1985; Dorman 1991; Eklund 1986; Falk 1989; Feighner 1985; Geretsegger 1995; Guillibert 1989; Gwirtsman 1983; Hoyberg 1996; Hutchinson 1991; Katona 1999; Kyle 1998; La Pia 1992; Nugent 1979; Pelicier 1993; Phanjoo 1991; Rahman 1991; Siegfried 1986; Scardigali 1982; Smeraldi 1998). Where terms describing individual side effects were similar, they were combined. This occurred in four circumstances: The terms 'anxiety', 'agitation', 'restlessness', 'excitability' and 'nervousness' were combined as 'anxiety'. 'Vertigo' and 'dizziness' were combined as 'dizziness'. 'Fatigue', 'drowsiness' and 'somnolence' were combined as 'drowsiness'. 'Nausea' and 'vomiting' were combined as 'nausea and vomiting'.
Dose of Drugs A number of trials employed a fixed dose drug regime, often increasing the dose over a number of weeks, reaching the prescribed dose within 2‐4 weeks. More trials employed varying dosages of antidepressants. The dose was usually titrated by the clinician according to response and side effect tolerability. Dose range varied considerably, both within studies and between studies. The doses of antidepressants used in trials included within the efficacy analysis are tabled Table 1.
1. Antidepressant dosage.
| Antidepressant | Fixed Dose (daily) | Varying Dose (daily) |
| Amitriptyline | Nugent 1979 (150mgs). Hutchinson 1991 (100mgs) | Hoyberg 1996 (upto 90mgs). Ather 1985 (up to 150mgs). Geretsegger 1995 (up to 150mgs). Kyle 1998 (up to 100mgs) |
| Citalopram | Kyle 1998 (up to 40mgs) | |
| Clomipramine | Guillibert 1989 (75mgs). Pelicier 1993 (60mgs) | Smeraldi 1998 (up to 100mgs) |
| Dothiepin | Rahman 1991 (up to 200mgs) | |
| Doxepin | Feighner 1985 (up to 200mgs). Gwitsman 1983 (30‐100mgs/ml). Mahapatra 1997 (up to 150mgs) | |
| Fluoxetine | La Pia 1992 (20mgs) | |
| Fluvoxamine | Bocksberger 1993 (up to 100mgs daily). Rahman 1991 (up to 200mgs daily) | |
| Imipramine | Dunningham 1994 (50‐200mgs). Eklund 1986 (50‐100mgs). Katona 1999 (50‐100mgs). | |
| Mianserin | Brion 1996 (30mgs). La Pia (40mgs). Scadigali 1982 (60mgs) | Eklund 1986 (50‐60mgs) |
| Mirtzpapine | Halikas 1995 (5‐35mgs) | |
| Moclobemide | Bocksberger 1993 (up to 300mgs) Dunningham 1994 (up to 450mgs). | |
| Nomifensine | Scardigali 1982 (150mgs) | |
| Nortripyline | Georgotas 1986 (50‐180ng/ml) | |
| Paroxetine | Dorman 1991 (30mgs). Guillibert 1989 (30mgs). Pellicier 1993 (20mgs). Hutchinson 1991 (30mgs) | Geretsegger 1995 (up to 30mgs) |
| Phenelzine | Georgotas 1986 (70% MAOI inhibition rate) | |
| Trazadone | Ather 1985 (100‐300mgs). Falk 1989 (up to 400mgs). Halikas 1995 (40‐280mgs). Smeraldi 1998 (up to 300mgs) | |
| Venlafaxine | Mahapatra 1997 (up to 150mgs) | |
| Viloxazine | Nugent 1979 (300mgs) | |
Trial design All trials were of parallel group design. Patients were randomly assigned to receive one of the trial drugs (or placebo) in appropriately designed trials. Data regarding placebo were excluded in examining efficacy and side effect profile. Three trials included more than two active drugs (Siegfried 1986; Smeraldi 1998). In those trials in which there were more than two active drugs compared, one drug was excluded from the meta‐analyses regarding efficacy.
Age Range Trials comparing patients as elderly, geriatric, senile or older adult used different minimum ages for this group. Some studies did not indicate age ranges (Tignol 1998), however all those that did included patients aged 55 or over. A minority of studies had limits on the upper age range (80 or 90 years old).
Diagnoses and severity of depression Twenty‐two studies employed DSM‐111, DSM‐111R or DSM‐IV diagnostic criteria for major depressive disorder and some included dysthymic disorder. Dorman 1991 included DSM‐III unipolar depression. Two trials used DSM‐III mixed depressive states (Katona 1999; La Pia 1992). Two studies (Mulsant 1998; Navarro 2001) used DSM‐IV criteria. Pelicier 1993 used Feighner's criteria (Feighner 1972). Nugent 1979; Scardigali 1982 and Tignol 1998 either failed to report or did not use validated diagnostic criteria. Entry diagnostic criteria were usually supported by the concomitant use of severity rating as defined by the Hamilton Depression Rating Scale (HDRS) (Hamilton 1967) or the Montgomery and Asberg Depression Rating Scale (MADRS) (Montgomery 1979). The 21, 24 and 17 item versions of the HDRS were used in 31 studies. Cut‐off severity scores included >15, >16, >17, >19. The MADRS was used in a similar fashion in six studies, employing cut‐offs of >23 and >29.
Outcome measures Efficacy Change in the HDRS was used as a primary outcome measures in the majority of studies (usually a reduction of 50% or to drop below a prespecified score). This was augmented by the Clinical Global Impression (CGI) in 21 studies. Change in MADRS score was employed as a primary outcome measure in six trials (Pelicier 1993; Phanjoo 1991; Kyle 1998; Smeraldi 1998; Bocksberger 1993; Brion 1996) and used in conjunction with the HDRS by De Ronchi 1998; Geretsegger 1995; Halikas 1995; Hoyberg 1996; Smeraldi 1998; Feighner 1985; Mahapatra 1997; Mulsant 1998; Navarro 2001; Tignol 1998. The Geriatric Depression Scale was used as a secondary outcome measure in two trials (La Pia 1992; Nair 1995). Other rating scales included: The Leeds Sleep Evaluation Questionnaire (no reference available), which was used by Dorman 1991. The Treatment Emergent Side Effect Scale (no reference available) was used by Falk 1989. The Raskin Scale (Feighner 1985) and the Zung Depression Scale (Zung 1965) were used by Georgotas 1986; Gwirtsman 1983; Halikas 1995; Pelicier 1993. The Wakefield Self Assessment Scale was used by Nugent 1979 as a secondary outcome measure. Eklund 1986 used a visual analogue scale and Guillibert 1989 used the Newcastle Scale as secondary outcome measures. Other than the listed scales and instruments, Siegfried 1986 examined the occurrence of specific drug related side effects, including change in cardiac status. No studies included outcomes of quality of life measures. Patients who discontinued, dropped out or died were assumed to have experienced no improvement in terms of depression severity.
Withdrawal rates In examining the withdrawal rates associated with each class of antidepressants, we examined both data pertaining to the 'overall withdrawal rates' (irrespective of cause) and withdrawal due to side effects (as described by the trialist). In presenting the 'overall withdrawal rates' we provided the context in which withdrawal rates due to side effects could be considered, to provide consistency with a related Cochrane review (Wilson 2005). In interpreting these results it is evident that 'overall withdrawal' was not a surrogate for side effect experience.
Side effects Due to the small size of the dataset, variety in description of side effects, variability in reporting and problems in grouping side effects by organ system, the data were presented in a qualitative format through percentages and ratios, so as to facilitate comparison between antidepressant classes, specifically avoiding formal analysis.
Study size Studies were both single and multi‐site, with the largest number of sites being nine (Mahapatra 1997); comparing venlafaxine with dothiepin. The following studies had 50 or more patients receiving each drug: Ather 1985; Brion 1996; Feighner 1985; Hoyberg 1996; Katona 1999; Kyle 1998; Mulsant 1998Schweizer 1998; Smeraldi 1998; Tignol 1998. All the other studies had less than 50 patients in either or both arms of the study.
Duration of trials Five trials had the shortest duration of four weeks. Two trials had a duration of five weeks and 12 trials lasted six weeks. Three trials lasted seven weeks and four trials lasted eight weeks. Of the remainder (for which the duration was available) De Ronchi 1998, a trial of fluoxetine compared with amitriptyline lasted 10 weeks. Three trials lasted 12 weeks; Dunningham 1994, a trial of moclobemide compared with imipramine, Mulsant 1998 a trial of nortriptyline compared with paroxetine and Navarro 2001, a trial of citalopram compared with nortriptyline. Brion 1996, a trial comparing tienepine with mianserin lasted 24 weeks.
Recruitment source and patient exclusions The following trials recruited patients from inpatient services: Bocksberger 1993; Eklund 1986; Geretsegger 1995; (older persons medical inpatient unit), Siegfried 1986 (older person acute medical inpatient unit and nursing home residents) and Nugent 1979 (females from an inpatient unit). The following recruited from both inpatient and out patient populations: Ather 1985; Hoyberg 1996; Katona 1999; La Pia 1992; Mahapatra 1997; Mulsant 1998; Navarro 2001; Phanjoo 1991; Tignol 1998. The studies that recruited from outpatient and community samples include: De Ronchi 1998; Dunningham 1994; Falk 1989; Feighner 1985; Georgotas 1986; Halikas 1995; Hutchinson 1991; Kyle 1998; Nair 1995; Pelicier 1993; Schweizer 1998; Smeraldi 1998. The remaining six studies failed to report population recruitment sources.
Risk of bias in included studies
All trials included in the review were classified as 'B', using the quality assessment criteria from the Cochrane Reviewers' Handbook (Alderson 2004). In most trials the quality of reporting was poor. Trials reported randomisation without any information on allocation concealment. A majority of trials reported dropouts and post randomisation exclusions. The majority of trials did not use the intent‐to‐treat approach. A significant number of trials failed to provide useable data due to lack of efficacy analysis or the omission of standard deviations. A number of studies also omitted basic information about the study population (gender, setting etc).
The 23‐item quality assessment instrument developed by Montcrieff 2001 was also used to assess the methodological quality of studies. Studies varied in score between 16 and 33 with a mean score of 23.04 (SD 6.18). There were no significant differences in quality between the types of studies or the age of the study.
Effects of interventions
Meta analyses were firstly conducted to compare efficacy and withdrawal rates between classes of antidepressants. We compared all TCAs (classical and related) with SSRIs. In subsequent subgroup analyses, we compared classical TCAs with SSRIs and TCA related antidepressants with SSRIs. Where data enabled comparisons of efficacy and withdrawal rates between TCAs, atypical antidepressants and MAOIs, further subgroup analyses were conducted. In the second part of the analysis we examined side effects by organ system and class of antidepressant, with findings presented descriptively. Side effect events were presented in ratio format of events experienced by 10 patients to enable comparison of side effects associated with each organ system between drug classes. We also conducted a qualitative analysis of individual side effects in terms of percentage of patients experiencing each side effect.
Efficacy All TCAs versus SSRIs Nine studies (De Ronchi 1998; Dorman 1991; Feighner 1985; Geretsegger 1995; Hutchinson 1991; Kyle 1998; Mulsant 1998; Navarro 2001; Pelicier 1993) included paroxetine, fluoxetine, and citalopram (SSRIs) and mianserin, doxepin, trazodone, amitriptyline, nortriptyline and clomipramine (TCAs). These trials generated 528 TCA recipients and 552 SSRI recipients. There was no difference in efficacy at the 5% level of significance between the drug classes (RR: 1.07, CI 0. 94 to 1.22). Only one trial generated continuous data (Falk 1989) and no significant differences were found in terms of change in depression severity between the two groups.
All TCAs versus MAOIs We were able to compare the efficacy of all TCAs with MAOIs. However, this meta‐analysis of two studies (Georgotas 1986; Nair 1995) only generated data on 121 patients receiving phenelzine and moclobemide (MAOIs) and nortriptyline (TCA) (RR: 1.16, CI 0.74 to 1.83). The lack of data makes any generalisation concerning the comparative efficacy of these groups of drugs unreliable. No data were generated with regard to continuous outcome variables.
All TCAs versus atypicals Four trials contributed to All TCAs versus atypical comparison (Halikas 1995; Hoyberg 1996; Mahapatra 1997; Smeraldi 1998). No differences were found between all the TCA (number of patients = 223) and atypical (number of patients = 161) when considering efficacy in terms of failure to recover (RR 0.84 CI 0.51 to 1.38). One trial (Hoyberg 1996) generated a small number of patients (n=91) to enable comparison in terms of continuous data; failing to show differences between the two groups of drugs.
SSRIs versus MAOIs Only one trial was found in this group (Bocksberger 1993) with 20 recipients in each arm, there was no significant difference between the groups (RR: 0.81 CI 0.55 to 1.20).
MAOIs versus atypicals No trials were found for this comparison
Classical TCAs versus SSRIs Seven studies (Feighner 1985; Geretsegger 1995; Hutchinson 1991; Kyle 1998; Mulsant 1998; Navarro 2001; Pelicier 1993) generated 388 patients receiving classical TCAs and 402 patients receiving SSRIs. No significant differences were found in terms of recovery (RR: 1.07, CI 0.93 to 1.24). Likewise, in the one study generating continuous data (De Ronchi 1998), no significant differences were found.
Related TCAs versus SSRIs The only study from which data could be extracted (Dorman 1991) generated less than 50 patients in each experimental arm (RR: 1.59, CI 1.07 to 2.35). Falk 1989 generated 25 patients in a trial comparing fluoxetine with trazodone and failed to demonstrate differences in terms of change in depression severity.
Heterogeneity A random effects model was used as statistical heterogeneity was found in the analysis. Heterogeneity was found in All TCAs versus atypicals (Chi squared 6.19, df=2, p=0.05) efficacy and withdrawal rate (Chisquared 18.18, df=7, p=0.01).
Publication bias A funnel plot failed to demonstrate clear evidence of publication bias due to insufficient data.
Withdrawal rates All TCAs versus SSRIs Fourteen studies (De Ronchi 1998; Dorman 1991; Falk 1989; Feighner 1985; Geretsegger 1995; Guillibert 1989; Hutchinson 1991; Kyle 1998; La Pia 1992; Mulsant 1998; Navarro 2001; Pelicier 1993; Phanjoo 1991; Rahman 1991) generated 651 TCA recipients and 677 SSRI recipients. The trials included mianserin, trazodone, doxepin, amitriptyline, imipramine, clomipramine, nortriptyline and dothiepin (TCAs) compared with paroxetine, fluoxetine, citalopram and fluvoxamine (SSRIs). Meta analysis demonstrated that patients receiving SSRIs were less likely to be withdrawn in general (RR: 1.23, CI 1.05 to 1.43), and more specifically, due to side effects (RR: 1.36, CI 1.09 to 1.70). All TCAs versus MAOIs In comparing withdrawal rates (irrespective of cause) of all TCAs recipients with MAOI recipients three studies were identified (Dunningham 1994, Georgotas 1986, Nair 1995). They compared moclobemide and phenelzine (MAOIs; n=88) with nortriptyline and imipramine (TCAs: n= 93). No differences in withdrawal rates were noted (RR: 0.91, CI 0.64 to 1.29). The Dunningham 1994 trail did not generate data of sufficient quality to be included in the comparison of withdrawal due to side effects. This analysis (Georgotas 1986, Nair 1995) compared moclobemide and phenelzine (MAOIs: an=58) and nortriptyline (TCA an=63). TCA recipients were more likely to be withdrawn due to side effects (RR: 2.27, CI 0.44 to 11.81).
All TCAs versus atypical antidepressants The systematic search of the literature failed to generate more than one trial examining identical drugs that did not fall into the drug classes as defined by the British National Formulary. The heterogeneity of drugs included within the atypical antidepressant class limits the relevance of combining these drugs as one class of antidepressants. However the review authors wished to determine whether these newer antidepressants were less likely to be associated with withdrawal due to side effects when compared with more established TCAs.
Eight studies (Brion 1996, Halikas 1995, Hoyberg 1996, Katona 1999, Mahapatra 1997, Schweizer 1998, Smeraldi 1998, Tignol 1998) included six different antidepressant drugs of differing pharmacological groups including tianeptine, mirtazepine, reboxetine, venlafaxine, buspirone, and milnaciprin (typicals: 748 patients). They were compared with mianserin, trazodone, amitriptyline, dothiepin, imipramine, and clomipramine (TCAs: 709 patients). Analysis of withdrawal rates showed no significant differences between these groups (RR: 0.96, CI: 0.75 to 1.24). Similar findings were noted when we examined withdrawal due to side effects (RR: 1.36, CI 0.96 to 1.94).
Further subgroup analysis of classical and related TCA antidepressants demonstrated that subjects receiving the 'atypical' antidepressants tianeptine and mirtazepine were more likely to be withdrawn from trials (irrespective of cause) when compared to patients receiving trazodone and mianserin (related TCAs) (RR: 1.41, CI 1.16 to 1.71). However these findings were not reflected in different withdrawal rates induced by drug side effects (RR: 1.38, CI 0.74 to 2.59). No differences were found between classical TCAs and the 'atypical' group in terms of withdrawal.
SSRIs versus MAOIs Only on trial generated data to be incorporated in efficacy analysis (Bocksberger 1993), using both continuous and dichotomous data. The forty patients included within the trial failed to show significant differences between the groups of drugs.
SSRIs versus atypicals No trials were found for this comparison
Classical TCAs versus SSRIs Further analysis was conducted in order to examine sub‐classes of TCAs in relationship to SSRIs. We examined amitriptyline, clomipramine, doxepin and dothiepin (classical TCAs) with paroxetine, fluoxetine and citalopram (SSRIs). In the analysis concerning withdrawal rates irrespective of cause we included ten studies (De Ronchi 1998; Feighner 1985; Geretsegger 1995; Guillibert 1989; Hutchinson 1991; Kyle 1998; Mulsant 1998; Navarro 2001; Pelicier 1993; Rahman 1991). These generated 565 classical TCA recipients and 589 SSRI recipients. The findings show an increased total withdrawal rate for recipients of classical TCAs compared to SSRI recipients (RR: 1.24, CI 1.05 to 1.46). In comparing withdrawal rates due to side effects; eight studies generated 505 recipients of classical TCAs and 528 recipients of SSRIs. The findings were similar (RR: 1.40, CI 1.11 to 1.77).
Classical TCAs versus atypicals We were unable to demonstrate differences between groups in terms of withdrawal rates (RR: 0.84 CI 0.70 to 1.01). Six trials provided data for this analysis (Hoyberg 1996; Katona 1999; Schweizer 1998; Smeraldi 1998; Tignol 1998) providing 560 recipients of classical TCAs compared to 500 recipients of atypicals. Withdrawal due to side effects also failed to show a difference RR: 1.27 CI 0.73 to 2.22). Related TCAs versus SSRIs In the next subgroup analysis we compared antidepressants related to TCAs with SSRIs. Four studies (Dorman 1991; Falk 1989; La Pia 1992; Phanjoo 1991) generated data relating to mianserin and trazodone (TCA related) and paroxetine, fluvoxamine and fluoxetine (SSRIs). Eighty‐six patients received TCA related drugs and 88 received SSRIs. Meta analysis demonstrated that there was no significant differences in either total withdrawal rates (RR: 1.49, CI 0.74 to 2.98) or withdrawal due to side effects (RR: 1.07, CI 0.43 to 2.70).
Assessment frequency, number and withdrawal rates Williams 2000 has demonstrated that withdrawal rates of patients from trials are dependent on the duration of the interval between assessments. We examined this issue in the context of the current study. As predicted by Williams 2000, we found an inverse relationship between duration of interval between assessments and patient withdrawal (irrespective of reason of withdrawal), (Pearson Correlation, 2 tailed ‐0.71). However, no correlations were found between interval duration and withdrawal due to side effects.
Publication bias A funnel plot failed to demonstrate clear evidence of publication bias.
Side effects by drug group As patients are likely to suffer from more than one side effect simultaneously, side effect events were reported qualitatively in the form of the ratio of number of side effect events experienced by ten patients. The trials generated enough data to describe the patient: side effect ratios between patients receiving classical TCAs and SSRIs as one comparison, and classical TCAs and related TCAs as a second comparison. The ratios are provided in Additional Table 2. Individual side effects are expressed by organ system as a percentage of patients potentially exposed by organ system.
2. Patient side effect event ratios by drug class.
| System | Classical TCAs | SSRIs | Classical TCAs | Related TCAs |
| CVS | 10:<1 | 10:<1 | 10:1.1 | 10:1.4 |
| GIT | 10:4.6 | 10:2.9 | 10:4.1 | 10:4.1 |
| Neuropsych | 10:4.1 | 10:2.3 | 10:7.4 | 10:6.5 |
| Dermatological | 10:<1 | 10:<1 | 10:1 | 10:<1 |
Classical TCAs versus SSRIs Seven trials (Feighner 1985; Geretsegger 1995; Guillibert 1989; Hutchinson 1991; Kyle 1998; Pelicier 1993; Rahman 1991) were examined. Four of these generated data that could be included in the analysis (Hutchinson 1991, Kyle 1998, Pelicier 1993, Rahman 1991). Classical TCAs included amitriptyline, clomipramine, doxepin, and dothiepin. The four studies generated a total population of 294 patients receiving classical TCAs and 307 patients receiving paroxetine, fluvoxamine and citalopram (SSRIs).
Cardiovascular side effects Hypotension was the only cardiovascular side effect recorded: with one event experienced by patients taking classical TCAs and four events by patients taking SSRIs.
Gastrointestinal side effects The experience of 'dry mouth' significantly contributed to the difference between ratios in the two drug classes (28% of classical TCA recipients compared to 7% of SSRI recipients). However nausea and vomiting was more common in SSRI recipients (17% of SSRI recipients compared to 7.5% of classical TCA recipients). Constipation was a common side effect, experienced by 7.4% of classical TCA recipients and 4.5% of SSRI recipients. Diarrhoea was experienced by 3% (classical TCA recipients) and 1.3% (SSRI recipients). Anorexia was the least frequent side effect, experienced by 2.7% (classical TCA group) and 1.6% (SSRI group). No other side effects were reported by more than 1% of either group.
Neuropsychiatric side effects 15.3% of classical TCA recipients and 6.5% of SSRI recipients experienced drowsiness and somnolence. Dizziness was experienced by 12.2% and 7.8% by classical TCA and SSRI recipients respectively. Lethargy was the next most commonly experienced side effect, with 4.4% of TCA recipients and less than 1% of SSRI recipients experiencing the side effect. Four percent of patients receiving classical TCAs and 2.6% of SSRIs recipients experienced sleep disturbance. Three percent of classical TCA recipients and 1.6% of SSRI recipients experienced tremor and less than 1% of each drug group experienced anxiety. No other neuropsychiatric side effects were recorded.
Dermatological side effects Sweating was the only side effect reported in either drug group with 1.7% of classical TCA recipients and less than 1% or SSRI recipients experiencing it.
Classical TCAs versus TCA related antidepressants Seven studies generated data of sufficient quality to be included in the analysis (Ather 1985, Eklund 1986, Gwirtsman 1983; Nugent 1979; Scardigali 1982; Siegfried 1986; Smeraldi 1998). These trials included trazodone, maprotiline, mianserin, viloxazine (TCA related drugs), generating 206 patients; and compared them with amitriptyline, doxepin and clomipramine (classical TCAs), generating 231 patients.
Cardiovascular side effects Hypotension was the commonest side effect experienced by both groups (classical TCA recipients 3.9%, TCA related recipients 3.4%). Hypertension was experienced by just over 1% of each group (classical TCA 1.3%, TCA related 1.45%). ECG abnormality (classical TCA 4.3%, TCA related 0.97%) and palpitations (classical TCA; 1.3%, TCA related 0.5%) were experienced by greater percentages of classical TCA recipients compared with TCA related recipients. 5.8% of TCA related recipients and 0% classical TCA recipients experienced bradycardia. Tachycardia was experienced by 6.9% of classical TCA recipients compared with 0% of TCA related recipients.
Gastrointestinal side effects 'Dry mouth ' was the commonest experienced side effect (classical TCA 16.9%, TCA related 26.2%). This was followed by constipation experienced by 11.2% of classical TCA recipients and 10.6% of TCA related recipients. A significant minority of patients receiving classical TCAs experienced nausea and vomiting compared to those receiving TCA related drugs (classical TCA 9.5%, TCA related 4.3%). Weight gain was experienced by 1.3% classical TCA recipients compared to 2.4% of TCA related recipients. Increased salivation was experienced by 1.3% classical TCA recipients and 1.5% TCA related recipients. Less than 1% of each group experienced diarrhoea.
Neuropsychiatric side effects Drowsiness was the commonest side effect experienced by 15.6% of classical TCA recipients and 18.9% of TCA related recipients. This was closely followed by sleep disturbance experienced by 15.6% classical TCA recipients and 14% of TCA related recipients. Over 10% of the sample experienced dizziness (12.6% of classical TCA recipients and 11.6% of TCA related recipients). Anxiety was experienced by approximately 1: 10 of the study population (8.2% of classical TCA recipients and 10.2% of TCA related recipients). Tremor was experienced by 3.5% of classical TCA sample and 7.8% of TCA related sample. Blurred vision was experienced by 3.5% classical TCA recipients and 5.3% of TCA related recipients. 4.3% of classical TCA recipients and 5.3% of TCA related recipients experienced rigidity and stiffness. 4.8% classical TCA recipients and 2.4% of TCA related recipients experienced headache. Syncope was experienced by just over 1% of each group (classical TCA 1.3%, TCA related 1.4%) and a similar percentage experienced 'confusion' (classical TCA 0.9%, TCA related 1.5%). Paraesthesia was experienced by 0.4% of patients receiving classical TCAs.
Dermatological side effects Seven patients (3%) receiving classical TCAs and 5 (2.4%) receiving TCA related drugs experienced skin rashes.
Discussion
In undertaking this meta‐analysis we have conducted a systematic search of the literature and identified randomised controlled trials comparing antidepressants in the treatment of depression on older people. We have grouped together in accordance with the British National Formulary groupings so as to enable comparison between commonly used antidepressants in terms of efficacy, withdrawal and side effect profile.
The diversity of trial design and drug pharmacology present particular difficulties in the design of the review and interpretation of the findings. These issues are of considerable importance when considering the grouping of antidepressants, the efficacy, withdrawal rate and side effect analysis. The grouping of 'atypical' antidepressants is particularly vulnerable to criticism in that none of the antidepressants are of similar pharmacological design and all are noted for their differing pharmacological actions. We have drawn attention to this within the results and methodological sections of the review. Despite the obvious problems associated with this aspect of the meta‐analysis the reviewers thought that it would be of clinical merit to examine these drugs as a group and compare them (in terms of side effects) to the more well established TCAs with view to examining them as a group of 'newer' antidepressants likely to be used in the treatment of older people. The trials were carried out on patients drawn from inpatient populations, out patient clinics, community volunteers and residents of nursing and care homes. The relatively small number of studies (when examined by antidepressant group) restricted the nature and validity of conducting subgroup analysis on these differing populations, including the potential effect of differing different types of depression and the experience of physical illness. Likewise, the small number of studies and the size of patient populations involved prohibit comparison between some of the drug groups.
In examining comparative efficacy data our findings have been limited through small sample sizes and poverty of data. Previous studies have demonstrated all these drug classes are superior to placebo (Wilson 2005). However we were able to compare efficacy between TCAs and SSRIs finding no difference in efficacy based on 'recovery', however the total withdrawal rate was significant less favouring SSRIs . Similar results are obtained when comparing classical TCAs with SSRIs and atypical drugs. However, in the latter case (mirtazepine compared with trazodone and venlafaxine compared with clomipramine) only two trials were included, providing a combined population of 223 patients, limiting the implications of the findings.
Very few of the trials employed standardised instruments in the reporting of side effects, and many of the side effects experienced by patients prescribed these drugs may readily be confused with symptoms and signs of depression in this age group. Notably, only one study defined side effects as a change in the patients' experience since commencing the antidepressants. The lack of standardised instruments in qualifying and quantifying side effect experiences promotes significant problems in undertaking a meta‐analysis. It is evident that trialists place differing emphasis on capturing side effect data when designing trials, which is likely to explain some of the differences in their findings. As a consequence, the reviewers have included an analysis of withdrawal rates. We extracted data from trials that described the cause of withdrawal, identifying numbers of patients identified by the trialists as being withdrawn specifically due to antidepressant side effects. These data included patients that had died but had also been identified as suffering from side effects during the trials. We excluded patients who died that were described as being free of side effect during whilst taking the antidepressants. Analysis pertaining to comparative withdrawal rates due to side effects does not provide detail concerning quantity or severity of the side effects experience of individual patients. This analysis is presented in the context of an analysis of 'overall withdrawal' (irrespective of cause).
In examining the qualitative experience of antidepressant recipients, the review authors were presented with an array of poorly defined terms with little information concerning severity or frequency of side effects. In the analysis we used terms as used by the trialists. When terms were combined or altered, these have been described in the methodology section of the review. We have grouped side effects into broad categories to enable a more comprehensive, qualitative description of the experiences of patients receiving antidepressants. The categories are loosely based on organ system. The authors accept that categories are poorly defined and offer little inherent legitimacy. Consequently we have been careful not to conduct formal analysis in comparing side effect prevalence rates, and have merely expressed our findings as ratios of the number of side effect events experienced by ten patients. We have provided percentages of patients experiencing individual side effects when possible.
The review has generated some interesting findings. It is evident that when the tricyclic antidepressants are considered as one group and compared with SSRIs (over 1000 patients included within the analysis) they have a higher rate of withdrawal due to side effects. The TCA group included mianserin and trazodone as TCA related drugs; and amitriptyline, imipramine, clomipramine, dothiepin and doxepin as classical TCAs. In comparing classical TCAs (amitriptyline, clomipramine, doxepin, and dothiepin) with SSRIs (paroxetine, citalopram, fluoxetine and fluvoxamine), both classes are of similar efficacy. However, classical TCA recipients are more likely to be withdrawn due to side effects. These findings are reflected in the differing side effect profiles generated by each drug class. Classical TCA recipients experienced more gastrointestinal (a ratio of 4.6 side effect experiences for each 10 TCA recipients compared to 2.9 experienced by 10 SSRI recipients) and neuropsychiatric side effects (4.1 side effects experienced by 10 classical TCA recipients compared to 2.3 side effects experienced by 10 SSRI recipients). The most notable differences in side effect experiences include 28% of classical TCA recipients experiencing dry mouth compared to 7% of SSRI recipients. However nausea and vomiting was experienced by a greater percentage of SSRI recipients.
The findings differ when comparing TCA related drugs with SSRIs. Some caution should be taken in interpreting these findings. The four studies only generated 174 patients, receiving mianserin and trazodone (related TCAs) or paroxetine, fluvoxamine and fluoxetine (SSRIs). There was no difference in withdrawal rates. The trials failed to generate enough data of sufficient quality to enable an analysis of comparative efficacy or a break down of the side effect profile in relationship to these studies.
We were able to examine the side effect profiles experienced by patients involved in trials comparing classical TCAs and TCA related antidepressants. Four hundred and thirty seven patients participated in these trials and were recipients of four different TCA related antidepressants and four classical tricyclics. There was relatively little difference in terms of side effect: patient ratio. There were slight differences in terms of the experiences of individual side effects with slightly greater percentage of classical TCA recipients experiencing ECG abnormalities and bradycardia. The drug classes have a similar profile in terms of neuropsychiatric side effects. Drowsiness, sleep disturbance, dizziness and anxiety were most frequently experienced side effects with tremor, blurred vision, stiffness, headache syncope and confusion occasionally experienced. Both groups experienced similar profiles of gastrointestinal side effects. Dry mouth and constipation were the commonest side effects, followed by nausea and vomiting and weight gain.
Comparing withdrawal rates of TCAs with newer, 'atypical' antidepressants is of limited value as a consequence of the heterogeneity of drugs within the 'atypical' group. When these newer antidepressants are collectively considered, our findings suggest that they are similar to classical TCAs in terms of withdrawal rates. However, as already mentioned, caution must be taken in drawing conclusions with clinical implications as more comparative trials are required before their relative tolerability can be judged. The meta analysis of withdrawal rates of MAOIs in comparison with TCAs was hampered by the few trials available. Not only were the patient numbers small but relatively few drugs were included. Hence the findings and potential clinical implications should be considered with due caution.
Authors' conclusions
Implications for practice.
The clinical implications of our findings are tentative in view of the difficulties in generalising results from trials into the general population. With this caveat the findings suggest that SSRIs and TCAs are of equal efficacy. Older patients receiving TCA related antidepressants have a similar withdrawal rate compared to SSRIs, both in terms of overall withdrawal rate irrespective of cause, and withdrawal specifically due to side effect experience (as defined by the trialists). In contrast, when All TCAs and classical TCAs trials are analysed significantly higher withdrawal rates than those receiving SSRIs. Complementing this, there is evidence of differing side effect profiles, especially when comparing gastrointestinal side effects between SSRIs and classical TCAs. However it must be noted that when the two subgroups of TCAs (classical and related TCAs) are compared in terms of side effect ratios we could establish no real differences. A cautious interpretation of these findings is that TCA related antidepressants might offer a relatively low side effect profile compared to the classical TCAs and may be associated with better tolerability. The withdrawal rate of TCA related antidepressants appears similar to that of SSRIs, and provided they are of similar efficacy, they may offer the clinician and patient an acceptable alternative in those situations in which SSRIs are not acceptable.
Implications for research.
This review has been not been able to conduct all comparisons planned due to lack of or small numbers of trials or low numbers of patient participants. The diversity of pharmacological profile of drugs that have been grouped together and difficulty in categorising side effect experiences has caused difficulty in interpretation. The later issue is of particular importance in the context of older people in which both somatic symptoms of depression and concomitant physical illness are likely to mask the side effect profile of drugs. These issues demand focus in future research in this field. It is evident that older people are vulnerable to side effects, yet relatively few studies have examined this issue in this age group. Secondly, it is evident that standardised techniques should be adopted in identifying and quantifying side effect experiences. These techniques should be designed to cater for the identification of those effects that are most likely caused by the prescription of drugs, comparing the experience of the patient before drug prescription with that of the patient after the drug has been prescribed. The sensitivity and specificity of such techniques should be subjected to carefully designed studies in differing patient populations both with and without concomitant physical illness.
What's new
| Date | Event | Description |
|---|---|---|
| 1 November 2008 | Amended | Converted to new review format. |
History
Protocol first published: Issue 4, 1999 Review first published: Issue 1, 2006
| Date | Event | Description |
|---|---|---|
| 15 February 2006 | New citation required and conclusions have changed | Substantive amendment |
Acknowledgements
Cheshire & Wirral Partnership NHS Trust
Data and analyses
Comparison 1. All TCAs versus SSRIs.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Failed to recover | 9 | 1080 | Risk Ratio (M‐H, Random, 95% CI) | 1.07 [0.94, 1.22] |
| 2 Depression severity (HAM‐D Scale) | 2 | 90 | Mean Difference (IV, Random, 95% CI) | 2.41 [‐3.68, 8.50] |
| 3 Withdrawal due to side‐effects | 12 | 1207 | Risk Ratio (M‐H, Random, 95% CI) | 1.36 [1.09, 1.70] |
| 4 Total withdrawal rates | 14 | 1328 | Risk Ratio (M‐H, Random, 95% CI) | 1.23 [1.05, 1.43] |
1.1. Analysis.
Comparison 1 All TCAs versus SSRIs, Outcome 1 Failed to recover.
1.2. Analysis.
Comparison 1 All TCAs versus SSRIs, Outcome 2 Depression severity (HAM‐D Scale).
1.3. Analysis.
Comparison 1 All TCAs versus SSRIs, Outcome 3 Withdrawal due to side‐effects.
1.4. Analysis.
Comparison 1 All TCAs versus SSRIs, Outcome 4 Total withdrawal rates.
Comparison 2. All TCAs versus MAOIs.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Failed to recover | 2 | 121 | Risk Ratio (M‐H, Random, 95% CI) | 1.16 [0.74, 1.83] |
| 2 Depression severity (HAM‐D Scale) | 0 | 0 | Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 3 Withdrawal due to side effects | 2 | 121 | Risk Ratio (M‐H, Random, 95% CI) | 2.27 [0.44, 11.81] |
| 4 Total withdrawal rates | 3 | 181 | Risk Ratio (M‐H, Random, 95% CI) | 0.91 [0.64, 1.29] |
2.1. Analysis.
Comparison 2 All TCAs versus MAOIs, Outcome 1 Failed to recover.
2.3. Analysis.
Comparison 2 All TCAs versus MAOIs, Outcome 3 Withdrawal due to side effects.
2.4. Analysis.
Comparison 2 All TCAs versus MAOIs, Outcome 4 Total withdrawal rates.
Comparison 3. All TCAs versus Atypicals.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Failed to recover | 4 | 384 | Risk Ratio (M‐H, Random, 95% CI) | 0.84 [0.51, 1.38] |
| 2 Depression severity (HAM‐D Scale) | 1 | 91 | Mean Difference (IV, Random, 95% CI) | ‐3.30 [‐6.84, 0.24] |
| 3 Withdrawal due to side effects | 8 | 1456 | Risk Ratio (M‐H, Random, 95% CI) | 1.36 [0.96, 1.94] |
| 4 Total withdrawal rates | 8 | 1457 | Risk Ratio (M‐H, Random, 95% CI) | 0.96 [0.75, 1.24] |
3.1. Analysis.
Comparison 3 All TCAs versus Atypicals, Outcome 1 Failed to recover.
3.2. Analysis.
Comparison 3 All TCAs versus Atypicals, Outcome 2 Depression severity (HAM‐D Scale).
3.3. Analysis.
Comparison 3 All TCAs versus Atypicals, Outcome 3 Withdrawal due to side effects.
3.4. Analysis.
Comparison 3 All TCAs versus Atypicals, Outcome 4 Total withdrawal rates.
Comparison 4. SSRIs versus MAOIs.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Failed to recover | 1 | 40 | Risk Ratio (M‐H, Random, 95% CI) | 0.81 [0.55, 1.20] |
| 3 Withdrawal due to side effects | 1 | 40 | Risk Ratio (M‐H, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 4 Total withdrawal rates | 1 | 40 | Risk Ratio (M‐H, Random, 95% CI) | 2.0 [0.20, 20.33] |
4.1. Analysis.
Comparison 4 SSRIs versus MAOIs, Outcome 1 Failed to recover.
4.3. Analysis.
Comparison 4 SSRIs versus MAOIs, Outcome 3 Withdrawal due to side effects.
4.4. Analysis.
Comparison 4 SSRIs versus MAOIs, Outcome 4 Total withdrawal rates.
Comparison 5. Classical TCAs versus SSRIs.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Failed to recover | 7 | 790 | Risk Ratio (M‐H, Random, 95% CI) | 1.07 [0.93, 1.24] |
| 2 Depression severity (HAM‐D Scale) | 1 | 45 | Mean Difference (IV, Random, 95% CI) | 0.28 [‐4.92, 5.48] |
| 3 Withdrawal due to side effects | 8 | 1033 | Risk Ratio (M‐H, Random, 95% CI) | 1.40 [1.11, 1.77] |
| 4 Total withdrawal rates | 10 | 1154 | Risk Ratio (M‐H, Random, 95% CI) | 1.24 [1.05, 1.46] |
5.1. Analysis.
Comparison 5 Classical TCAs versus SSRIs, Outcome 1 Failed to recover.
5.2. Analysis.
Comparison 5 Classical TCAs versus SSRIs, Outcome 2 Depression severity (HAM‐D Scale).
5.3. Analysis.
Comparison 5 Classical TCAs versus SSRIs, Outcome 3 Withdrawal due to side effects.
5.4. Analysis.
Comparison 5 Classical TCAs versus SSRIs, Outcome 4 Total withdrawal rates.
Comparison 6. Related TCAs versus SSRIs.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Failed to recover | 1 | 57 | Risk Ratio (M‐H, Random, 95% CI) | 1.59 [1.07, 2.35] |
| 2 Depression severity (HAM‐D Scale) | 1 | 25 | Mean Difference (IV, Fixed, 95% CI) | 6.00 [‐0.34, 12.34] |
| 3 Withdrawal due to side effects | 4 | 174 | Risk Ratio (M‐H, Random, 95% CI) | 1.07 [0.43, 2.70] |
| 4 Total withdrawal rates | 4 | 174 | Risk Ratio (M‐H, Random, 95% CI) | 1.49 [0.74, 2.98] |
6.1. Analysis.
Comparison 6 Related TCAs versus SSRIs, Outcome 1 Failed to recover.
6.2. Analysis.
Comparison 6 Related TCAs versus SSRIs, Outcome 2 Depression severity (HAM‐D Scale).
6.3. Analysis.
Comparison 6 Related TCAs versus SSRIs, Outcome 3 Withdrawal due to side effects.
6.4. Analysis.
Comparison 6 Related TCAs versus SSRIs, Outcome 4 Total withdrawal rates.
Comparison 7. Classical TCAs versus Atypicals.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Failed to recover | 2 | 285 | Risk Ratio (M‐H, Random, 95% CI) | 0.99 [0.75, 1.30] |
| 2 Depression severity (HAM‐D Scale) | 1 | 91 | Mean Difference (IV, Fixed, 95% CI) | ‐3.30 [‐6.84, 0.24] |
| 3 Withdrawal due to side effects | 6 | 1060 | Risk Ratio (M‐H, Random, 95% CI) | 1.27 [0.73, 2.22] |
| 4 Total withdrawal rates | 6 | 1060 | Risk Ratio (M‐H, Random, 95% CI) | 0.84 [0.70, 1.01] |
7.1. Analysis.
Comparison 7 Classical TCAs versus Atypicals, Outcome 1 Failed to recover.
7.2. Analysis.
Comparison 7 Classical TCAs versus Atypicals, Outcome 2 Depression severity (HAM‐D Scale).
7.3. Analysis.
Comparison 7 Classical TCAs versus Atypicals, Outcome 3 Withdrawal due to side effects.
7.4. Analysis.
Comparison 7 Classical TCAs versus Atypicals, Outcome 4 Total withdrawal rates.
Comparison 8. Related TCAs versus Atypicals.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Failed to recover | 1 | 97 | Risk Ratio (M‐H, Random, 95% CI) | 0.64 [0.35, 1.18] |
| 2 Withdrawal due to side effects | 2 | 396 | Risk Ratio (M‐H, Random, 95% CI) | 1.38 [0.74, 2.59] |
| 3 Total withdrawal rates | 2 | 397 | Risk Ratio (M‐H, Random, 95% CI) | 1.41 [1.16, 1.71] |
8.1. Analysis.
Comparison 8 Related TCAs versus Atypicals, Outcome 1 Failed to recover.
8.2. Analysis.
Comparison 8 Related TCAs versus Atypicals, Outcome 2 Withdrawal due to side effects.
8.3. Analysis.
Comparison 8 Related TCAs versus Atypicals, Outcome 3 Total withdrawal rates.
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Ather 1985.
| Methods | Double blind RCT Concealment of allocation ‐ unclear Analysis ‐ n/a Active treatment ‐ 6 weeks | |
| Participants | Inclusion criteria 13+ HMD Age over 59 Country: UK Setting: hospital in or outpatients | |
| Interventions | Trazodone Versus Amitriptyline versus Diazepam | |
| Outcomes | Side effects 'Marked improvement assessed by physician' Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Bocksberger 1993.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 4 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depression and 20+ MADRS Age: over 65 Country: Switzerland Setting: inpatient | |
| Interventions | Fluvoxamine versus moclobemide | |
| Outcomes | Side effects MADRS Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Brion 1996.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Intent to treat Active treatment: 6 months | |
| Participants | Inclusion criteria: DSM IIIR, Major Depression and 24+ MADRS Age: over 70 Country: France Setting: General Medicine | |
| Interventions | Tianeptine versus mianserin | |
| Outcomes | Side effects Drop out HMD MADRS | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
De Ronchi 1998.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Active treatment 10 weeks | |
| Participants | Inclusion criteria: DSMIIIR major depressive disorder, HMD 16+. Age 60+ Country Italy Setting: Outpatients | |
| Interventions | Fluoxetine versus amitriptyline | |
| Outcomes | HMD Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Dorman 1991.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Unipolar Depression and 17+ HMD Age: over 65 Country: UK Setting: Outpatient | |
| Interventions | Paroxetine versus mianserin | |
| Outcomes | Side effects HMD Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Dunningham 1994.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Not Applicable Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depression and 18+ HMD Age: over 60 Country: Brazil Setting: Outpatient | |
| Interventions | Moclobemide versus imipramine | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Eklund 1986.
| Methods | Double blind RCT Concealment of allocation ‐ unclear Endpoint analysis Active treatment 4 weeks | |
| Participants | Inclusion criteria: 17+ HMDR primary illness Age: 60‐80 Country:Sweden /Netherlands Setting: unclear | |
| Interventions | Mianserin versus Imipramine | |
| Outcomes | Side effects Drop out HMD(21 item) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Falk 1989.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM III, Major Depressive unipolar episode of at lease 4 weeks, and 20+ HMD (21 item) Age: over 62 Country: USA Setting: Outpatient | |
| Interventions | Fluoxetine versus trazodone | |
| Outcomes | Side effects HMD (21 item) Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Feighner 1985.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Not applicable Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depression of at least 1 month, 20+ HMD Age: over 61 Country: USA Setting: Outpatient | |
| Interventions | Fluoxetine versus doxepin | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Georgotas 1986.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 7 weeks | |
| Participants | Inclusion criteria: RDC Major Depression and 16+ HMD Age: over 55 Country: USA Setting: Outpatient | |
| Interventions | Nortriptyline versus phenelzine | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Geretsegger 1995.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depression and 18+ HMD, inpatient for 3 weeks +, Age: over 65 Country: Germany & Austria Setting: Inpatient | |
| Interventions | Paroxetine versus amitriptyline | |
| Outcomes | Side effects HMD Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Guillibert 1989.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Not applicable Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depressive Disorder and 20+ HMD (21 item) (Washout responders declined if 20% reduction) Age: over 65 Country: France Setting: Outpatient | |
| Interventions | Paroxetine versus clomipramine | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Gwirtsman 1983.
| Methods | Double blind RCT Concealment of allocation ‐ unclear Analysis ‐ n/a Active treatment 6 weeks | |
| Participants | Inclusion criteria: DSM‐III, Major Depression HDR 17+ Age: 55+ Country: USA Setting: unclear | |
| Interventions | Maprotiline versus Doxepin | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Halikas 1995.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM III, Major Depressive Episode and 17+ HMD (17 item) Age: Over 55 Country: USA Setting: Private psychiatric practice | |
| Interventions | Mirtazapine versus trazodone placebo controlled | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Hoyberg 1996.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depression and 18+ HMD (21 item) Age: over 55 | |
| Interventions | Mirtazapine versus Trazedone versus placebo | |
| Outcomes | Side effects Drop out HMD MADRS | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Hutchinson 1991.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depression and 18+ HMD (21 item) Age: over 65 Country: UK Setting: Primary Care | |
| Interventions | Paroxetine versus amitriptyline | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Katona 1999.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 8 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depressive disorder or Dysthymia and 17+ HMD, Mini Mental State 21+ Age: Over 65 Country: Australia, Belgium, Brazil, France, Germany, Ireland & UK Setting: Inpatient + Outpatient | |
| Interventions | Reboxetine versus imipramine | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Kyle 1998.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 8 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depressive disorder and 22+ MADRS Age: Over 65 Country: UK Setting: General Practice | |
| Interventions | Clitalopram and amitriptyline | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
La Pia 1992.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depressive disorder and 18+ HMD (21 item) Age: 60‐80 Country: Italy Setting: Inpatient + Outpatient | |
| Interventions | Fluoxetine versus mianserin | |
| Outcomes | Side effects Drop out HMD, GDS | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Mahapatra 1997.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Intent to treat Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depression, symptoms for 1 month + and 18+ HMD (21 item) minimum of 23 on Mini Mental State Examination Age: 64 ‐ 87 Country: UK + Netherlands Setting: Inpatients, Outpatients day treatment centre patients | |
| Interventions | Venlafaxine versus dothiepin | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Mulsant 1998.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Intent to treat Active treatment: 12 weeks | |
| Participants | Inclusion criteria: Major Depressive episode, and 15+ HMD (17 item) minimum of 15 plus on Mini Mental State Examination Age: 60+ Country: USA Setting: Inpatients + outpatients | |
| Interventions | Nortiptyline versus Paroxetine | |
| Outcomes | Drop out Side effects | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Nair 1995.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 7 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depressive disorder and 17+ HMD (17 item) Age: Over 60 Country: Canada, Denmar & UK Setting: Unknown | |
| Interventions | Moclobemide versus nortriptyline versus placebo | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Navarro 2001.
| Methods | Single blind (doctor blind to treatment) RCT. Concealment of allocation ‐ D Analysis: Modified Intent to treat Active treatment: 12 weeks | |
| Participants | Inclusion criteria: Unipolar Major Depression DSM IV, HMD >20 minimum of 25 on Mini Mental State Examination Age: 60+ Country: Spain Setting: Inpatients, Outpatients | |
| Interventions | Citalopram versus Nortriptyline | |
| Outcomes | Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Nugent 1979.
| Methods | Double blind RCT Concealment of allocation: unclear Analysis: n/a Active treatment: 4 weeks | |
| Participants | Inclusion criteria: depressive illness Age: 60+ Females Country: UK Setting Inpatients | |
| Interventions | Viloxazine versus amitriptyline | |
| Outcomes | Side effects Drop out Hamilton | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Pelicier 1993.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Not applicable Active treatment: 5 weeks | |
| Participants | Inclusion criteria: Reactive depression using Feighner criteria Age: over 60 Country: France Setting: Outpatient | |
| Interventions | Paroxeting versus clomipramine | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Phanjoo 1991.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depression and 30+ MADRS Age: over 65 Country: UK Setting: Inpatient + outpatients | |
| Interventions | Fluvoxamine versus mianserin | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Rahman 1991.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depression and 30+ MADRS Age: over 65 Country: UK Setting: Inpatient | |
| Interventions | Fluvoxamine versus dothiepin | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Scardigali 1982.
| Methods | Double blind RCT Concealment of allocation unclear Analysis n/a Active treatment: 4 weeks | |
| Participants | Inclusion criteria: endogenous, reactive, involutional depression Age: 'elderly' Country: Italy Setting: unclear | |
| Interventions | Mianserin versus trazodone versus nomifensine | |
| Outcomes | Side effects Beck Self Rating Scale CGI | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Schweizer 1998.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 8 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depressive disorder for minimum of 3 months, 18+ HMD Age: Over 65 Country: USA Setting: Primary care | |
| Interventions | Buspirone versus imipramine | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Siegfried 1986.
| Methods | Double blind RCT Concealment of allocation ‐ unclear Analysis: n/a Active treatment: 4 weeks | |
| Participants | Inclusion criteria: DSM‐III major depression single or recurrent, HDR 17+ Age: 65 + Country: Germany Setting: Combined inpatient old aged people's home and geriatric cline | |
| Interventions | Maprotiline versus mianserin versis nomifensine | |
| Outcomes | Side effects Drop out HDRS | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Smeraldi 1998.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 6 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depressive disorder for at least 1 month and 22+ MADRS Age:Over 65 Country: Italy Setting: Geriatric Inpatients + Outpatients | |
| Interventions | Venlafaxine versus clomipramine versus trazodone | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Tignol 1998.
| Methods | Double blind RCT. Concealment of allocation ‐ unclear. Analysis: Endpoint Active treatment: 8 weeks | |
| Participants | Inclusion criteria: DSM IIIR, Major Depressive disorder and 16+ HMD (17 item) Age: Over 65 Country: France Setting: Inpatient + Outpatient | |
| Interventions | Milnacipran versus imipramine | |
| Outcomes | Side effects Drop out | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Ahlfors 1988 | Mixed adult / aged population |
| Altamura 1989a | No extractable data |
| Altamura 1989b | No extractable data |
| Amore 2001 | Mixed adult / aged population |
| Aslan 1986 | No extractable data |
| Behnke 1992 | Includes bipolar patients |
| Bjerre 1981 | Dose‐finding study |
| Bornstein 1979 | Mixed adult / aged population |
| Botros 1989 | Mixed adult / aged population |
| Branconnier 1983 | No extractable data |
| Branconnier 1987 | Mixed adult / aged population |
| Brodie 1975 | Combination therapy |
| Burch 1983 | Crossover study |
| Burke 1967 | Mixed adult / aged population |
| Butters 2000 | Not all patients depressed |
| Casacchia 1994 | No extractable data |
| Cassano 1998 | Includes bipolar patients |
| Cohn 1984 | No extractable comparable data |
| Cohn 1990 | Nomifensine + 1 |
| Cohn 1991 | No extractable comparable data |
| Dachary 1985 | Mixed adult / aged population |
| De Leon 1977 | Not elderly |
| De Vanna 1990 | No extractable data |
| Delaunay 1978 | Mixed adult / aged population |
| Dell'Agnello 2001 | Open‐label study |
| Dunner 1992 | Re‐analysis |
| Evans 1981 | Mixed adult / aged population |
| Fabian 1999 | Not all patients depressed |
| Fabre 1983 | Only one active drug |
| Fairbairn 1989 | No extractable data |
| Fairweather 1993 | No extractable data |
| Feighner 1990 | No extractable data |
| Finkel 1995 | Sub‐analysis of trial |
| Flicker 1998 | No extractable comparable data |
| Forrest 1964 | Mixed adult / aged population |
| Freed 1996 | Mixed adult / aged population |
| Gattaz 1996 | No extractable data |
| Gentili 1984 | Includes bipolar patients |
| Gerner 1980 | No extractable data |
| Goldstein 1982 | Nomifensine + 1 |
| Gonella 1990 | Mixed adult / aged population |
| Green 1999 | Not RCT |
| Haider 1968 | Mixed adult / aged population |
| Harding 1973 | Mixed adult / aged population |
| Hebenstreit 1988 | Mixed adult / aged population |
| Hell 1994 | Mixed adult / aged population |
| Hostmaelingen 1989 | No extractable data |
| Jarvik 1982 | Not RCT |
| Jessel 1981 | No extractable data |
| Kane 1983 | No extractable comparable data |
| Karlsson 2000 | Mixed diagnosis |
| Katona 1999b | No extractable comparable data |
| Katona 1998 | No extractable comparable data |
| Kerr 1984a | Mixed adult / aged population |
| Khan 1981 | No extractable comparable data |
| Kivella 1987 | Only one active drug |
| Koncevoj 1989 | Includes patients with dementia |
| Koran 1995 | Only one active drug |
| Laghrissie‐Thode '95 | No extractable data |
| Lapierre 1991 | Includes bipolar patients |
| Lauritzen 1994 | CCT Not RCT |
| Lauritzen 1996a | Mixed adult / aged population |
| Lauritzen 1996b | Mixed diagnosis |
| Lipsedge 1971 | Mixed adult / aged population |
| Malsch 1996 | Includes bipolar patients |
| Mamo 2000 | No extractable comparable data |
| Marais 1974 | Mixed adult / aged population |
| McEntee 1996 | No extractable comparable data |
| Meignan‐Debray 1990 | Only one active drug |
| Meredith 1994 | Nomifensine + 1 |
| Middleton 1975 | Not RCT |
| Moizeszowicz 1977 | Dementia patients included |
| Moller 1993 | Includes bipolar patients |
| Moller 2000 | Mixed adult / aged population |
| Monteleone 1994 | No extractable data |
| Montgomery 1981 | No extractable data |
| Montgomery 1983 | Not elderly |
| Murphy 1975b | Mixed adult / aged population |
| Murphy 2000 | No extractable data |
| Nair 1993 | No extractable data |
| Newhouse 1988 | Not RCT |
| Newhouse 1996 | No extractable data |
| Nielsen 1993 | Mixed adult / aged population |
| Pancheri 1994 | Includes bipolar patients |
| Poldinger 1982b | Mixed adult / aged population |
| Pollock 1998 | No extractable comparable data |
| Rickels 1994c | Mixed adult / aged population |
| Robertson 1994 | Mixed adult / aged population |
| Robinson 2000 | Mixed adult / aged population |
| Roose 1987 | Mixed adult / aged population |
| Roose 1994 | Re‐analysis |
| Roose 1998 | Mixed adult / aged population |
| Rothblum 1982 | Combination therapy |
| Sacchetti 1997 | Mixed adult / aged population |
| Scarzella 1985 | Not elderly |
| Schatzberg 2000 | No extractable data |
| Schifano 1990 | No extractable comparable data |
| Schiwy 1989a | Dose‐finding study |
| Schiwy 1989b | Dose‐finding study |
| Schneider 1998a | |
| Schneider 1998b | |
| Schone 1994 | No extractable comparable data |
| Stanley 1998 | No extractable data |
| Stewart 1968 | Mixed adult / aged population |
| Stoppe 1998 | No extractable data |
| Strik 1998 | Mixed adult / aged population |
| Taragano 1997 | Mixed diagnosis |
| Thayssen 1981 | No comparative data |
| Tourigny‐Rivard 1996 | No extractable data |
| Volz 1995 | Not elderly |
| Volz 1997a | Mixed adult / aged population |
| Von Bauer 1969 | Mixed diagnosis |
| Waite 1986 | No extractable data |
| Wakelin 1986 | Re‐analysis |
| Weber 2000 | No extractable comparable data |
| Weihls 2000 | No extractable comparable data |
| Weissman 1992 | Combination therapy |
| Wilkins 1989 | No extractable data |
| Zapletalek 1990 | Mixed adult / aged population |
Contributions of authors
Mottram PG, searching, reviewing, data extraction, statistics, writing Wilson KCM, reviewing, data extraction, writing Strobl J, reviewing and data extraction
Sources of support
Internal sources
Cheshire & Wirral Partnership NHS Trust R&D Funding, UK.
External sources
No sources of support supplied
Declarations of interest
None
Edited (no change to conclusions)
References
References to studies included in this review
Ather 1985 {published data only}
- Ather SA, Ankier SI, Middleton RS. A double blind evaluation of Trazodone in the treatmentof depression in the elderly. British Journal of Clinical Practice 1985;6:192‐9. [PubMed] [Google Scholar]
Bocksberger 1993 {published data only}
- Bocksberger JP, Gachoud JP, Richard J, Dick P. Comparison of the efficacy of moclobemide and fluvoxamine in elderly patients with a severe depressive episode. European Psychiatry 1993;8:319‐24. [Google Scholar]
Brion 1996 {published data only}
- Brion S, Audrain S, Bodinat C. Episode of severe depression in subjects over 70 years of age ‐ efficacy and acceptability of Tianeptine and Mianserine [Episodes depressifs majeurs de sujets ages de plus de 70 ans ‐ Evaluation de l'efficacite et de l'acceptabilite de la tianeptine et de la mianserine]. Press Medicale 1996;25:461‐8. [PubMed] [Google Scholar]
De Ronchi 1998 {published data only}
- Ronchi D, Rucci P, Lodi M, Raqvaglia G, Forti P, Volterra V. Fluoxetine and amitriptyline in elderly depressed patients. A 10‐week, double‐blind study on course of neurocognitive adverse events and depressive symptoms. Archives of Gerontology and Geriatrics 1998;6 Suppl 1:125‐40. [Google Scholar]
Dorman 1991 {published data only}
- Dorman T. Sleep and Paroxetine:A comparison with Mianserin in elderly depressed patients. Journal of Clinical Psychopharmacology 1992;6(4):53‐8. [PubMed] [Google Scholar]
Dunningham 1994 {published data only}
- Dunningham W, Aguiar WM, Lourdes Costa Pinto M. A double‐blind Brazilian study of efficacy and safety of moclobemide versus imipramine in the treatment of patients with geriatic depression [Estudo brasileiro duplo‐cego da eficacia e seguranca da moclobemida versus imipramina no tratamento de pacientes com depressao geriatrica]. Arquivos Brasileiros de Medicina 1994;68(6):402‐5. [Google Scholar]
Eklund 1986 {published data only}
- Eklund K, Dunbar GC, Pinder RM, Steffensen K. Mianserin and imipramine in the treatment of elderly depressed patients. Acta Psychiatrica Scandinavica. Supplementum 1985;320:54‐9. [PubMed] [Google Scholar]
Falk 1989 {published data only}
- Falk WE, Roenbaum JF, Otto MW, Zusky PM, Weilburg JB, Nixon RA. Fluoxetine versus Trazodone in depressed geriatric patients. Journal of Geriatric Psychiatry and Neurology 1989;2(4):208‐14. [DOI] [PubMed] [Google Scholar]
Feighner 1985 {published data only}
- Feighner JP, Boyer WF, Henricksen GG, Pambakian RA, Doroski VS. A controlled trial of Adinazolam versus Desipramine in geriatric depression. International Clinical Psychopharmacology 1990;5:227‐32. [DOI] [PubMed] [Google Scholar]
- Feighner JP, Cohn JB. Double blind comparative trials of Fluoxetine and Doxepin in Geriatric patients with major depressive disorder. Journal of Clinical Psychiatry 1985;46(3 sec 2):20‐5. [PubMed] [Google Scholar]
Georgotas 1986 {published data only}
- Georgotas A, McCue R, Reisberg B, Ferris SH, Nagachandran N, Chang I, et al. The effect of mood changes and antidepressants on the cognitive capacity of elderly depressed patients. International Psychogeriatrics 1989;1(2):135‐43. [DOI] [PubMed] [Google Scholar]
- Georgotas A, McCue RE, Cooper T, Chang I, Mir P, Welkowitz J. Clinical predictors of response to antidepresants in elderly patients. Biological Psychiatry 1987;22:733‐40. [DOI] [PubMed] [Google Scholar]
- Georgotas A, McCue RE, Cooper TB, Nagachandran N, Friedhoff A. Factors affecting the delay of antidepressant effect in responders to Nortriptyline and Phenelzine. Psychiatry Research 1989;28:1‐9. [DOI] [PubMed] [Google Scholar]
- Georgotas A, McCue RE, Friedman E, Cooper TB. A placebo controlled comparison of the effect of Nortiptyline and Phenelzine on orthostatic hypotension in elderly depressed patients. Journal of Clinical Psychopharmacology 1987;7:413‐6. [PubMed] [Google Scholar]
- Georgotas A, McCue RE, Friedman E, Cooper TB. Electrocardiographic effects of Nortriptyline, Phenelzine, and placebo under optimal treatment conditions. American Journal of Psychiatry 1987;144(6):798‐801. [DOI] [PubMed] [Google Scholar]
- Georgotas A, McCue RE, Hapworth W, Friedman E, Kim OM, Welkowitz J, et al. Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly. Biological Psychiatry 1986;21:1155‐66. [DOI] [PubMed] [Google Scholar]
- Georgotas A, Stokes P, McCue RE, Dubow A, Welkowitz J, Friedman E, et al. The usefulness of DST in predicting response to antidepressants: a placebo controlled study. Journal of Affective Disorders 1986;11:21‐8. [DOI] [PubMed] [Google Scholar]
- McCue RE, Georgotas A, Nagachandran N, Basir MA, Go EA, Suckow RF, et al. Plasma levels of Nortriptyline and 10 hydroxynortriptyline and treatment related electrocardiographic changes in the elderly depressed. Journal of Psychiatric Research 1989;23(1):73‐9. [DOI] [PubMed] [Google Scholar]
- McCue RE, Georgotas A, Suckow RF, Cooper TB. 10 Hydroxynortriptyline and treatment effects in elderly depressed patients. Journal of Neuropsychiatry 1989;1(2):176‐80. [DOI] [PubMed] [Google Scholar]
Geretsegger 1995 {published data only}
- Geretsegger, Stuppaeck CH, Mair M, Platz, Fartacek R, Heim M. Mulitcenter double blind study of paroxetine and amitrtiptyline in elderly depressed inpatients. Psychopharmacology 1995;119:277‐81. [DOI] [PubMed] [Google Scholar]
Guillibert 1989 {published data only}
- Guillibert E, Pelicier Y, Archambault JC, Chabannes JP, Clerc G, Desvilles M, et al. A double blind multicenter study of paroxetine versus clomipramine in depressed elderly patients. Acta Psychiatrica Scandinavica. Supplementum 1989;350:132‐4. [DOI] [PubMed] [Google Scholar]
Gwirtsman 1983 {published data only}
- Ahles S, Gwirtsman H, Halaris A, Shah P, Schwarcz G, Hill MA. Comparative cardiac effects of Maprotiline and Doxepin in elderly depressed patients. Journal of Clinical Psychiatry 1984;45:460‐5. [PubMed] [Google Scholar]
- Gwirtsman HE, Ahles S, Halaris A, DeMet E, Hill MA. Therapeutic superiority of Maprotiline versus Doxepin in geriatric depression. Journal of Clinical Psychiatry 1983;44:449‐53. [PubMed] [Google Scholar]
Halikas 1995 {published data only}
- Halikas JA. Org 3770 (Mirtazapine)versus Trazodone:A placebo controlled trial in depressed elderly patients. Human Psychopharmacology 1995;10:S125‐33. [Google Scholar]
Hoyberg 1996 {published data only}
- Hoyberg OJ, Maragakis B, Mullin J, Norum D, Stordall E, Ekdahl P, et al. A double blind multicenter comparison of mirtazapine and amitriptyline in elderly depressed patients. Acta Psychiatrica Scandinavica 1996;93:184‐90. [DOI] [PubMed] [Google Scholar]
Hutchinson 1991 {published data only}
- Hutchinson D R, Tong S, Moon CAL, Vince M, Clarke A. Paroxetine in the treatment of elderly depressed patients in general practice:a double blind comparison with Amitriptyline. International Clinical Psychopharmacology 1991;6(4):43‐51. [DOI] [PubMed] [Google Scholar]
Katona 1999 {published data only}
- Katona C, Bercoff E, Chiu E, Tack P, Versiani M, Woelk H. Reboxetine versus imipramine in the treatment of elderly patients with depressive disorders: a double‐blind randomised trial. Journal of Affective Disorders 1999;55:203‐13. [DOI] [PubMed] [Google Scholar]
Kyle 1998 {published data only}
- Kyle CJ, Petersen HE, Overo KF. Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patient treated in general practice. Depression and Anxiety 1998;8:147‐53. [PubMed] [Google Scholar]
La Pia 1992 {published data only}
- Pia S, Giorgio D, Ciriello R, Sannino A, Simone L, Paoletti C, et al. Evaluation of the efficacy, tolerability and therapeutic profile of Fluoxetine versus Mianserin in the treatment of depressive disorders in the elderly. Current Therapeutic Research, Clinical and Experimental 1992;52(6):847‐58. [Google Scholar]
Mahapatra 1997 {published data only}
- Mahapatra SN, Hackett D. A randomised double blind parallel group comparison of Venlafaxine and Dothiepin in geriatric patients with major depression. International Journal of Clinical Practice 1997;51(4):209‐13. [PubMed] [Google Scholar]
Mulsant 1998 {published data only}
- Mulsant BH, Pollock BG, Nebes R, Sweet RA, French C, Stack J, et al. A randomized double‐blind comparison of nortriptyline and paroxetine in older derpessed pateints. 11th Annual Meeting of the American Association for Geriatric Psychiatry. San Diego, California, USA. 8th 11th March. 1998.
Nair 1995 {published data only}
- Nair NPV, Amin M, Schwartz G, Dastoor D, Thavundayil JX, Mirmiran J, et al. A comparison of the cardiac safety and therapeutic efficacy of Trimipramine versus Doxepin in geriatric depressed patients. Journal of American Geriatric Society 1993;41:863‐7. [DOI] [PubMed] [Google Scholar]
Navarro 2001 {published data only}
- Navarro V, Gasto C, Torres X, Marcos T, Pintor L. Citalopram versus nortriptyline in late‐life depression: a 12‐week randomized single‐blind study. Acta Psychiatrica Scandinavica 2001;103(6):435‐40. [DOI] [PubMed] [Google Scholar]
Nugent 1979 {published data only}
- Nugent D. A double blind study of Viloxazine(Vivalan) and Amitriptyline in depressed geriatric patients. Clincal Trials Journal 1979;16(1):13‐7. [Google Scholar]
Pelicier 1993 {published data only}
- Pelicier Y, Schaeffer P. Multicenter double‐blind study comparing the efficacy and tolerance of paroxetinw and clomipramine in reactive depression in the elderly patients [Etude multicentrique en double aveugle comparant l'efficacite et la tolerance de la paroxetine et de la clomipramine dans la depression reactionnelle du sujet age]. L'Encephale 1993;19:257‐61. [PubMed] [Google Scholar]
Phanjoo 1991 {published data only}
- Phanjoo AL, Wonnacott S, Hodgson A. A double blind comparative multicentre study of fluoxetine and mianserin in the treatment of major depressive episode in elderly people. Acta Psychiatrica Scandinavica 1991;83:476‐9. [DOI] [PubMed] [Google Scholar]
Rahman 1991 {published data only}
- Rahman MK, Jakhtar MJ, Savla NC, Sharma RR, Kellett JM, Asford JJ. A double blind randomised comparison of Fluvoxamine with Dothiepin in the treatment of depression in elderly patients. British Journal of Clinical Practice 1991;45(4):255‐8. [PubMed] [Google Scholar]
Scardigali 1982 {published data only}
- Scardigli G, Jans G. Comparative double blind study on efficacy and side effects of Trazodone, Nomifensine, Mianserin in elderly patients. Advances in Biochemical Psychopharmacology 1982;32:229‐36. [PubMed] [Google Scholar]
Schweizer 1998 {published data only}
- Schweizer E, Rickels K, Hassman H. A double blind placebo controlled comparison of Imipramine and Buspirone in the treatment of major depression in the elderly in the community. Psychopharmacology Bulletin 1994;30(4):639. [Google Scholar]
- Schweizer E, Rickels K, Hassman H, Garcia‐Espana F. Buspirone and Imipramine for the treatment of major depression in the elderly. Journal of Clinical Psychiatry 1998;59:175‐83. [DOI] [PubMed] [Google Scholar]
Siegfried 1986 {published data only}
- Siegfried K, O'Connolly M. Cognitive and Psychomotor effects of different antidepressants in the treatment of old age depression. International Clinical Psychopharmacology 1986;1:231‐43. [DOI] [PubMed] [Google Scholar]
Smeraldi 1998 {published data only}
- Smeraldi E, Fortunato R, Crespi G. Double‐blind, randomized study of venlafaxine, clomipramine and trazodone in geriatric patients with major depression. Primary Care Psychiatry 1998;4(4):189‐95. [Google Scholar]
Tignol 1998 {published data only}
- Tignol J, Domenech J, Chartres C, Leger JM, Pletan JM, Tonelli I, et al. Double blind study of the efficacy and safety of Milnacipran and Imipramine in elderly patients wih major depressive episode. Acta Psychiatrica Scandinavica 1998;97:157‐65. [DOI] [PubMed] [Google Scholar]
References to studies excluded from this review
Ahlfors 1988 {published data only}
- Ahlfors UG, Elovaara S, Harma P, Suoniemi I, Heikkila L, Nummi K, et al. Clinical multicentre study of citalopram compared double‐blindly with mianserin in depressed patients in Finland. Nordic Journal of Psychiatry ‐ Nordisk Psykiatrisk Tidsskrift 1988;42(3):201‐10. [Google Scholar]
Altamura 1989a {published data only}
- Altamura AC, Mauri MC, Rudas N, Carpiniello B, Montanini R, Perini M, et al. Clinical activity and tolerability of Trazodone mianserin and Amitriptyline in elderly subjects with major depression A controlled mulicentre trial. Clinical Neuropharmacology 1989;12 Suppl 1:S25‐33. [DOI] [PubMed] [Google Scholar]
Altamura 1989b {published data only (unpublished sought but not used)}
- Altamura AC, Mauri MC, Colacurcio R, Scapicchio PL, Hadjchristos C, Carucci G, et al. Trazodone in late life depressive states:a double blind mulicenter study versus amitriptyline and mianserin. Psychopharmacology 1988;95:S34‐6. [DOI] [PubMed] [Google Scholar]
Amore 2001 {published data only}
- Amore M, Jori MC. Faster response on amisulpride 50 mg versus sertraline 50‐100 mg in patients with dysthymia or double depression: A randomized, double‐blind, parallel group study. International Clinical Psychopharmacology 2001;16(6):317‐24. [DOI] [PubMed] [Google Scholar]
Aslan 1986 {published data only}
- Aslan A, Balaceanu C, Manoiu A, Erdos M. A double‐blind study on the antidepressive effects of Gerovital H3 and Aslavital in the elderly. Romanian Journal of Gerontology and Geriatrics 1986;7(2):79‐86. [Google Scholar]
Behnke 1992 {published data only}
- Behnke K, Mejer‐Nielsen B, Korner A, Arup P, Geisler A, Sastre‐Y‐Hernandez M, et al. Rolipram versus nortriptyline in gerontopsychiatric inpatients with major depression. Nordic Journal of Psychiatry ‐ Nordisk Psykiatrisk Tidsskrift 1992;46:407‐11. [Google Scholar]
Bjerre 1981 {published data only}
- Bjerre M, Gram LF, Kragh Sorensen P, Kristensen CB, Pedersen OL, Moller M, et al. Dose‐dependent kinetics of imipramine in elderly patients. Psychopharmacology 1981;75(4):354‐7. [DOI] [PubMed] [Google Scholar]
Bornstein 1979 {published data only}
- Bornstein S. Cross‐over trial comparing the antidepressant effects of amineptine and maprotiline. Current Medical Research and Opinion 1979;6(2):107‐10. [DOI] [PubMed] [Google Scholar]
Botros 1989 {published data only}
- Botros WA, Ankier SI, Priest RG, McManus IC, Steinert J, Samir ZY. Clinical assessment and performance tasks in depression: a comparison of amitriptyline and trazodone. British Journal of Psychiatry 1989;155:479‐82. [DOI] [PubMed] [Google Scholar]
Branconnier 1983 {published data only}
- Branconnier RJ, Cole JO, Ghazvinian S, Spera KF, Oxenkrug GF, Bass JL. Clinical Pharmacology of Bupropion and Imipramine in elderly depressives. Journal of Clinical Psychiatry 1983;44(5 sec 2):130‐3. [PubMed] [Google Scholar]
Branconnier 1987 {published data only}
- Branconnier RJ, Harto NE, Dessain EC, Spera KF, McNiff ME. Speech blockage, memory impairment, and age: a prospective comparison of amitriptyline and maprotiline. Psychopharmacology Bulletin 1987;23(1):230‐4. [PubMed] [Google Scholar]
Brodie 1975 {published data only}
- Brodie NH, McGhie RL, O'Hara H, Valle‐Jones JC, Schiff AA. Anxiety/Depression in elderly patients ‐ A double blind comparative study of Fluphenazine/Nortriptyline and Promazine. Practitioner 1975;215:660‐4. [PubMed] [Google Scholar]
Burch 1983 {published data only}
- Burch JE. The demethylation of amitriptyline: a cross‐over study of steady‐state plasma levels of amitriptyline and nortriptyline in depressed patients. Psychopharmacology 1983;80(3):254‐8. [DOI] [PubMed] [Google Scholar]
Burke 1967 {published data only}
- Burke BV, Sainsbury MJ, Mezo BA. A comparative trial of amitriptyline and trimipramine in the treatment of depression. Medical Journal of Australia 1967;1(24):1216‐8. [DOI] [PubMed] [Google Scholar]
Butters 2000 {published data only}
- Butters MA, Becker JT, Nebes RD, Zmuda MD, Mulsant BH, Pollock BG, et al. Changes in cognitive functioning following treatment of late‐life depression. American Joournal of Psychiatry 2000;157(12):1949‐54. [DOI] [PubMed] [Google Scholar]
Casacchia 1994 {published data only}
- Casacchia M, Bolino F, Marola W, Pirro R, Nivoli G, Rapisarda V, et al. Controlled multicentre study of teniloxazine in mild depression of the elderly. New Trends in Experimental and Clinical Psychiatry 1994;10(4):187‐92. [Google Scholar]
Cassano 1998 {published data only}
- Cassano GB, Cioni P, Crosignani A, Fazzari G, Ferrari G, Fornaro P, et al. A multicentre, couble‐blind comparison of befazodone and maprotiline in the treatment of depression of the elderly. XXI Collegium Internationale Neuro Psychopharmacologicum. Glasgow, Scotland, 1998.
Cohn 1984 {published data only}
- Cohn JB, Varga L, Lyford A. A two‐center double‐blind study of nomifensine, imipramine, and placebo in depressed geriatric outpatients. Journal of Clinical Psychiatry 1984;45(4 Pt 2):68‐72. [PubMed] [Google Scholar]
Cohn 1990 {published data only}
- Cohn CK, Shrivastava R, Mendels J, Cohn JB, Fabre LF, Claghorn JJ, et al. Double blind multicenter comparison of Sertraline and Amitriptyline in elderly depressed patients. Journal of Clinical Psychiatry 1990;51(12 Suppl B):28‐33. [PubMed] [Google Scholar]
Cohn 1991 {published data only}
- Cohn J, Claghorn J, Ostrow D. A comparative trial of Trimipramine and Doxepin in depressed elderly patients. Advances in Therapy 1991;8(2):92‐102. [Google Scholar]
Dachary 1985 {published data only}
- Dachary JM, Darondel A, Ernst J, Vauterin C. A comparative clinical trial on prothiaden fort 75 MG(TM) in hospitalized or ambulatory patients [Essai clinique comparatif du prothiaden fort 75mg (TM) en milieu hospitalier et ambulatoire]. Psychologie Medicale 1985;17(1):137‐44. [Google Scholar]
De Leon 1977 {published data only}
- DeLeon O, Kravcio JT, Sanchez C. Double‐blind trial of 2 antidepressive drugs [Ensayo doble ciego con dos antidepresivos]. Acta Psiquiatrica y Psicologica de America Latina 1977;23(3):215‐20. [PubMed] [Google Scholar]
De Vanna 1990 {published data only}
- Vanna M, Kummer J, Agnoli A, Gentili P, Lorizio A, Ananad R. Moclobemide compared with second generation antidepressants in elderly people. Acta Psychiatrica Scandinavica. Supplementum 1990;360:64‐6. [DOI] [PubMed] [Google Scholar]
Delaunay 1978 {published data only}
- Delaunay J, Meynard J. Clinical and comparative trial of dosulepin and amitriptyline [Essai clinique et comparatif de la Dosulepine et de l'Amitriptyline.]. Annales Medico‐Psychologiques 1978;136(10):1201‐7. [PubMed] [Google Scholar]
Dell'Agnello 2001 {published data only}
- Dell'Agnello G, Ceravolo R, Nuti A, Bellini G, Piccinni A, D'Avino C, et al. SSRIs do not worsen Parkinson's disease: evidence from an open‐label, prospective study. Clinical Neuropharmacology 2001;24(4):221‐7. [DOI] [PubMed] [Google Scholar]
Dunner 1992 {published data only}
- Dunner DL, Cohn JB, Walshe T 3rd, Cohn CK, Feighner JP, Fieve RR, et al. Two combined multicenter double blind studies of Paroxetine and Doxepin in geriatric patients with major depression. Journal of Clinical Psychiatry 1992;53(2 Suppl):57‐60. [PubMed] [Google Scholar]
Evans 1981 {published data only}
- Evans L, Cox J. A comparative study of the therapeutic effect and cardiotoxicity of dothiepin HCl and doxepin HCl in reactive depression. Progress in Neuro‐Psychopharmacology 1981;5(4):389‐93. [DOI] [PubMed] [Google Scholar]
Fabian 1999 {published data only}
- Fabian TJ, Kroboth PD, Butters MA, et al. Are DHEA and/or DHEA‐S concentrations associated with remission of depression or improvements in mental status scores in older adults. 12th Annual Meeting of the American Association for Geriatric Psychiatry; 14 17 March, 1999; New Orleans LA. 1999.
Fabre 1983 {published data only}
- Fabre LF, Brodie HK, Garver D, Zung WW. A multicenter evaluation of bupropion versus placebo in hospitalized depressed patients. Journal of Clinical Psychiatry 1983;44:88‐94. [PubMed] [Google Scholar]
Fairbairn 1989 {published data only}
- Fairbairn AF, George K, Dorman T. Lofepramine versus dothiepin in the treatment of depression in elderly patients. British Journal of Clinical Practice 1989;43:55‐60. [PubMed] [Google Scholar]
Fairweather 1993 {published data only}
- Fairweather DB, Kerr JS, Harrison DA, Moon CA, Hindmarch I. A double blind comparison of the effects of Fluoxetine and Amitriptyline on cognitive function in elderly depressed patients. Human Psychopharmacology 1993;8:41‐7. [Google Scholar]
Feighner 1990 {published data only}
- Feighner JP, Boyer WF, Hendrickson GG, Pambakian RA, Doroski VS. A controlled trial of adinazolam versus disipramine in geriatric depresion. International Clinical Psychopharmacology 1990;5(3):227‐32. [DOI] [PubMed] [Google Scholar]
Finkel 1995 {published data only}
- Finkel S, Richter E. Double‐blind comparison of sertraline and nortriptyline in late‐life depression. 8th ECNP (European College of Neuropsychopharmacology) Congress, Venice, Italy. 1995.
Flicker 1998 {published data only}
- Flicker C, Anderson G, Bayer L. A placebo controlled study of citalopram in the treatment of post stroke depression. 11th Annual Meeting of the American Association for Geriatric Psychiatry. San Diego, CA. 8th 11th March. 1998.
Forrest 1964 {published data only}
- Forrest AD, Affleck JW, Gibb IA, Priest RG. Comparative trial of nortriptyline and amitriptyline. Scottish Medical Journal 1964;9:341‐4. [DOI] [PubMed] [Google Scholar]
Freed 1996 {published data only}
- Freed E, George T, Goldney R, Lambert T, Tiller J. A double‐blind multicentre comparison of paroxetine and amitriptyline in Australian general‐practice. XXth Collegium Internationale Neuro psychopharmacologicum, Melbourne, Australia. 1996.
- Freed E, Goldney R, Lambert T, Tiller J, Johnston R. A double‐blind, multicentre study to assess the tolerability and efficacy of paroxetine compared with amitriptyline in the treatment of depressed patients in Australian general practice. Australian and New Zealand Journal of Psychiatry 1999;33(3):416‐21. [DOI] [PubMed] [Google Scholar]
Gattaz 1996 {published data only}
- Gattaz WF, Maras Schmidt AA, Low Bahro HM, Kohnen dittmann RW, Wolff Berger RM, Riemann D. Efficacy and Safety of Fluoxetine versus Trimipramine in Geriatric Depression. Xth World Congress of Psychiatry. Madrid, Spain, 1996.
Gentili 1984 {published data only}
- Gentili P, Maria F, Vanna M, Drago F, Omer LM, Ismail S. Diclofensine in the treatment of depressed geriatric hospitalized patients: A placebo‐controlled double‐blind trial. Current Therapeutic Research, Clinical and Experimental 1984;35(3):386‐95. [Google Scholar]
Gerner 1980 {published data only}
- Gerner R, Estabrook W, Steuer J, Jarvik L. Treatment of geriatric depression with Trazodone, Imipramine, and placebo:a double blind study. Journal of Clinical Psychiatry 1980;41(6):216‐9. [PubMed] [Google Scholar]
- Gerner R, Estabrook W, Steuer J, Waltuch L, Kakkar P, Jarvik L. A placebo controlled double blind study of Imipramine and Trazodone in geriatric depression. Psychopathology in the Aged 1980;69:167‐82. [PubMed] [Google Scholar]
- Hayes RL, Gerner RH, Fairbanks L, Moran M, Waltuch L. Findings in geriatric depressives given Trazodone, placebo or Imipramine. Journal of Clinical Psychiatry 1983;44:180‐3. [PubMed] [Google Scholar]
Goldstein 1982 {published data only}
- Goldstein SE, Birnbom F, Laliberte R. Nomifensine in the treatment of depressed geriatric patients. Jounal of Clinical Psychiatry 1982;43(7):287‐9. [PubMed] [Google Scholar]
Gonella 1990 {published data only}
- Gonella G, Baignoli G, Ecari U. Fluvoxamine and imipramine in the treatment of depressive patients: a double‐blind controlled study. Current Medical Research and Opinion 1990;12(3):177‐84. [DOI] [PubMed] [Google Scholar]
Green 1999 {published data only}
- Green TD, Reynolds CF3rd, Mulsant BH, Pollcock BG, Miller MD, Houck PR, et al. Accelerating antidepressant response in geriatric depression: a post hoc comparison of combined sleep deprivation and paroxetine versus monotherapy with paroxetine, nortirptyline, or placebo.. Journal of Geriatric Psychiatry and neurology 1999;12(2):67‐71. [DOI] [PubMed] [Google Scholar]
Haider 1968 {published data only}
- Haider I. A comparative investigation of desipramine and nortriptyline in the treatment of depression. British Journal of Psychiatry 1968;114(515):1293‐4. [DOI] [PubMed] [Google Scholar]
Harding 1973 {published data only}
- Harding T. A comparative clinical trial of oral clomipramine (Anafranil) against amitriptyline. Journal of International Medical Research 1973;1:343‐6. [Google Scholar]
Hebenstreit 1988 {published data only}
- Baumhackl U, Biziere K, Fischbach R, Geretsegger C, Hebenstreit G, Radmayr E, et al. Efficacy and tolerability of moclobemide compared with imipramine in depressive disorder (DSM‐III): an Austrian double‐blind, multicentre study. British Journal of Psychiatry 1989;155 Supp 6:78‐83. [PubMed] [Google Scholar]
- Biziere K, Berger M. Efficacy of a reversible monoamine oxidase‐A inhibitor versus imipramine in subgroups of depressed patients. Acta Psychiatrica Scandinavica. Supplementum 1990;360:59‐60. [DOI] [PubMed] [Google Scholar]
- Hebenstreit GF, et al. Efficacy and safety of moclobemide compared to imipramine in patients with major depression: Results of an Austrian multicenter double‐blind trial. Neurologija 1988;37 Suppl:25. [Google Scholar]
- Hebenstreit GF, et al. Efficacy, safety and tolerability of moclobemide compared with imipramine in the treatment of major depressive disorder. WPA Regional Symposium. 1990:114. [DOI] [PubMed]
- Hebenstreit GF, Loidl M, Baumhackl U, Gallhofer B, Geretsegger C, Radmayr E, et al. Efficacy and safety of moclobemide compared with imipramine in the treatment of major depressive disorder. Double‐blind multicenter study, Austria. Journal of Neural Transmission 1990;32 Suppl:177‐84. [DOI] [PubMed] [Google Scholar]
Hell 1994 {published data only}
- Hell D, Van H, Realini R, Fontana B, Woggon B, Moll E, et al. Moclobemide vs imipramine in the treatment of endogenous depressionComparison of efficacy, onset of action and tolerability [Moclobemid vs Imipramin bei endogener depression Vergleich von wirksamkeit, wirkungseintritt und vertraglichkeit]. Munchener Medizinische Wochenschrift 1994;136(27):424‐9. [Google Scholar]
Hostmaelingen 1989 {published data only}
- Hostmaelingen HJ, Asskilt O, Austad SG, Fjelheim J, Hostmaelingen EA, Kristiansen PH, et al. Primary care treatment of depression in the elderly:a double blind multi centre study of Flupenthixol (Fluanxol) and sustained release amitriptyline. Current Medical Research and Opinion 1989;11(9):593‐9. [DOI] [PubMed] [Google Scholar]
Jarvik 1982 {published data only}
- Jarvik LF, Mintz J, Steuer J, Gerner R. Treating geriatric depression: A 26 week interim analysis. Journal of the American Geriatrics Society 1982;30(11):713‐7. [DOI] [PubMed] [Google Scholar]
- Jarvik LF, Read SL, Mintz J, Neshkes RE. Pretreatment orthostatic hypotension in geriatric depression:Predictor of response to Imipramine and Doxepin. Journal of Clinical Psychopharmacology 1983;3(6):368‐71. [PubMed] [Google Scholar]
- Neshkes RE, Gerner R, Jarvik LF, Mintz J, Joseph J, Linde S, et al. Orthostatic effect of Imipramine and Doxepin in depressed geriatric outpatients. Journal of Clinical Psychopharmacology 1985;5(2):102‐6. [DOI] [PubMed] [Google Scholar]
Jessel 1981 {published data only}
- Jessel HJ, Jessel I, Wegener G. Therapy of elderly depressive patients. Lofepramine and amitriptyline under double‐blind conditions [Therapie von alteren depressiven Patienten. Lofepramin und Amitriptylin unter Doppelblindbedingungen]. Zeitschrift fur Allgemeinmedizin 1981;57(10):784‐8. [PubMed] [Google Scholar]
Kane 1983 {published data only}
- Kane JM, Cole K, Sarantakos S, Howard A, Borenstein M. Safety and efficacy of Bupropion in elderly patients:preliminary observations. Journal of Clinical Psychiatry 1983;44(5 Sec 2):134‐6. [PubMed] [Google Scholar]
Karlsson 2000 {published data only}
- Karlsson I, Godderis J, Augusto De Mendonca Lima C, et al. A randomised, double‐blind comparison of the efficacy and safety of citalopram compared to mianserin in elderly, depressed patients with or without mild to moderate dementia. International Journal of Geriatric Psychiatry 2000;15:295‐305. [DOI] [PubMed] [Google Scholar]
Katona 1999b {published data only}
- Katona C, Bercolff E, Chiu E, Tack P, Verisani M, Woelk H. Reboxetine versus imipramine in the treatment of elderly patients with depressive disorders: a double‐blind randomised trial. Journal of Affective Disorders 1999;55(2‐3):203‐13. [DOI] [PubMed] [Google Scholar]
Katona 1998 {published data only}
- Katona CL. Reboxetine is as effective and better tolerated than imipramine in elderly patients with depression. 151st Annual Meeting of the American Psychiatric Association. Toronto, Canada, 1998.
Kerr 1984a {published data only}
- Kerr TA, McClelland HA, Stephens DA, Ankier SI. Trazodone. A comparative clinical and predictive study. Acta Psychiatrica Scandinavica 1984;70(6):573‐7. [DOI] [PubMed] [Google Scholar]
Khan 1981 {published data only}
- Khan AU. A comparison of the therapeutic and cardiovascular effects of a single nightly dose of Prothiaden (Dothiepin,Dosulepin) and Lentizol (sustained release Amitriptyline) in depressed elderly patients. Journal of International Medical Research 1981;9:108‐12. [DOI] [PubMed] [Google Scholar]
Kivella 1987 {published data only}
- Kivela S L, Lehtomaki E. Sulperide and placebo in depressed elderly outpatients: A double‐blind study. International Journal of Geriatric Psychiatry 1987;2(4):255‐60. [Google Scholar]
Koncevoj 1989 {published data only}
- Koncevoj V, et al. Comparative study of age related effectiveness of tri and tetracyclic antidepressants. Zhurnal Nevropatologii I Psikhiatrii Imeni S. S. Korsakova 1991;91(9):58‐65. [PubMed] [Google Scholar]
Koran 1995 {published data only}
- Koran LM, Hamilton SH, Hertzman M, Meyers BS, Halaris AE, Tollefson GD, et al. Predicting response to fluoxetine in geriatric patients with major depression. Journal of Clinical Psychopharmacology 1995;15(6):421‐7. [DOI] [PubMed] [Google Scholar]
Laghrissie‐Thode '95 {published data only}
- Laghrissi ‐Thode F, Pollock BG, Miller MC, Mulsant BH, Altieri L, Finkel MS. Double blind comparison of Paroxetine and Nortriptyline on the Postural stability of late life depressed patients. Psychopharmacology Bulletin 1995;31(4):659‐63. [PubMed] [Google Scholar]
Lapierre 1991 {published data only}
- Lapierre YD. Controlling acute episodes of depression. Journal of Clinical Psychopharmacology 1991;6 Suppl2:23‐35. [DOI] [PubMed] [Google Scholar]
Lauritzen 1994 {published data only}
- Lauritzen L, Bendsen BB, Vilmar T, Bendsen EB, Lunde M, Bech P. Post‐stroke depression: combined treatment with imipramine or desipramine and mianserin a controlled clinical study. Psychopharmacology 1994;114(1):119‐22. [DOI] [PubMed] [Google Scholar]
Lauritzen 1996a {published data only}
- Bech P, Lauritzen L, Odgaard K, Clemmensen L, Lund M, Ohrstm J, et al. A comparison of paroxetine and imipramine in six months continuation therapy post ECT. 8th Congress of the Association of European Psychiatrists, London, UK. 1996.
- Bech P, Lauritzen L, Odgaard K, Clemmensen L, Lund M, Ohrstrom J. A comparison of paroxetine and imipramine in six months continuation therapy post ECT. Xth World Congress of Psychiatry, Madrid, Spain. 23rd‐28th August. 1996.
- Flint A. The impact of treatment resistance on depressive relapse following electroconvulsive therapy. Acta Psychiatrica Scandinavica 1997;96(5):405‐6. [DOI] [PubMed] [Google Scholar]
- Lauritzen L, Odgaard K, Clemmesen L, Lunde M, Ohrstrom J, Black C, et al. Relapse prevention by means of paroxetine in ECT‐treated patients with major depression: a comparison with imipramine and placebo in medium‐term continuation therapy. Acta Psychiatrica Scandinavica 1996;94(4):241‐51. [DOI] [PubMed] [Google Scholar]
Lauritzen 1996b {published data only}
- Flint A. The impact of treatment resistance on depressive relapse following electroconvulsive therapy. Acta Psychiatrica Scandinavica 1997;96(5):405‐6. [DOI] [PubMed] [Google Scholar]
- Lauritzen L, Odgaard K, Clemmesen L, Lunde M, Ohrstrom J, Black C, et al. Relapse prevention by means of paroxetine in ECT‐treated patients with major depression: a comparison with imipramine and placebo in medium‐term continuation therapy. Acta Psychiatrica Scandinavica 1996;94(4):241‐51. [DOI] [PubMed] [Google Scholar]
Lipsedge 1971 {published data only}
- Lipsedge MS, Rees WL. A double‐blind comparison of dothiepin and amitriptyline for the treatment of depression with anxiety. Psychopharmacologia 1971;19(2):153‐62. [DOI] [PubMed] [Google Scholar]
Malsch 1996 {published data only}
- Malsch U, Jager K, Schwalb B, Fischer W. Antidepressant therapy in geriatric patients ‐ Efficacy and cardiac tolerbility of Trimipramine vs Mianserin [Antidepressive therapie bei geriatrishcen patienten ‐ Wirksakeit und kardiale Vertraglichkeit von Trimipramin vs Mianserin]. Munchener Medizinische Wochenschrift 1996;138(34):29‐33. [Google Scholar]
- Malsch U, Jager K, Schwalb B, Fischer W. New Trends in Experimental Clinical Psychiatry. XXth Collegium Internationale Neuro‐psychopharmacologicum, Melbourne, Australia. 1996.
Mamo 2000 {published data only}
- Mamo DC, Sweet RA, Mulsant BH, Pollock BG, Miller MD, Stack JA, et al. Effect of nortriptyline and paroxetine on extrapyramidal signs and symptoms: a prospective double‐blind study in depressed elderly patients. Americal Journal of Geriatric Psychiatry 2000;8(3):226‐31. [PubMed] [Google Scholar]
Marais 1974 {published data only}
- Marais GF. Clinical evaluation of the antidepressants: maprotiline and amitriptyline A double‐blind controlled trial. South African Medical Journal 1974;48(36):1530‐2. [PubMed] [Google Scholar]
McEntee 1996 {published data only}
- McEntee W, Ko G, Richter E. Sertraline and Nortriptyline:Heart rate, cognitive improvement and quality of life in depressed elderly. XXth Collegium Internationale. 1996:P‐1‐8.
Meignan‐Debray 1990 {published data only}
- Meignan‐Debray S, Forette B, Roger M. Double‐blind trial of medifoxamine (Cledial) versus placebo in elderly peatients with depressive disorders [Etude comparative en double aveugle de la medifoxamine (Cledial ) versus placebo chez le sujet age deprime]. Psychologie Medicale 1990;22(9):883‐92. [Google Scholar]
Meredith 1994 {published data only}
- Meredith CH, Feighner JP, Hendrickson G. A double blind comparative evaluation of the efficacy and safety of Nomifensine, Impiramine and placebo in depressed geriatric outpatients. Journal of Clinical Psychiatry 1984;45(4 Sec 2):73‐77. [PubMed] [Google Scholar]
Middleton 1975 {published data only}
- Middleton RS. A comparison between Maprotiline (Ludiomil) and Imipramine in the treatment of depressive illness in the elderly. Journal of International Medical Research 1975;3 Suppl 2:79‐83. [Google Scholar]
Moizeszowicz 1977 {published data only}
- Moizeszowicz J, Subira S. Controlled trial of Nomifensin (HOE 984) and Viloxazine in the treatment of depression in the elderly. Journal of Clinical Pharmacology 1977;1:81‐3. [DOI] [PubMed] [Google Scholar]
Moller 1993 {published data only}
- Moller HJ, Muller H, Volz HP. How to assess the onset of antidepressant effect:comparison of global ratings and findings based on depression scales. Pharmacopsychiatry 1996;29:57‐62. [DOI] [PubMed] [Google Scholar]
- Moller HJ, Volz HP. Brofaromine in elderly major depressed patients ‐ a comparative trial versus Imipramine. European Neuropsychopharmacology 1993;3:501‐10. [DOI] [PubMed] [Google Scholar]
Moller 2000 {published data only}
- Moller HJ, Glaser K, Leverkus F, Gobel C. Double‐blind, multicenter comparative study of sertraline versus amitriptyline in outpatients with major depression. Pharmacopsychiatry 2000;33(6):206‐12. [DOI] [PubMed] [Google Scholar]
Monteleone 1994 {published data only}
- Monteleone P, Fabrazzo M. Blood levels of Mianserin and Amitriptyline and clinical response in aged depressed patients. Pharmacopsychiatry 1994;27:238‐41. [DOI] [PubMed] [Google Scholar]
Montgomery 1981 {published data only}
- Montgomersy SA, McAuley R, Rani SJ, Roy D, Montgomery DB. A double‐blind comparison of zimelidine and amitryptyline in endogenous depression. Acta Psychiatrica Scandinavica. Supplementum 1981;290:314‐27. [DOI] [PubMed] [Google Scholar]
Montgomery 1983 {published data only}
- Montgomery S A, Roy D, Wynne Willson S, Robinson C, Montgomery DB. Plasma levels and clinical response with imipramine in a study comparing efficacy with mianserin and nomifensine. British Journal of Clinical Pharmacology 1983;15 Suppl 2:205‐11. [DOI] [PMC free article] [PubMed] [Google Scholar]
Murphy 1975b {published data only}
- Murphy JE. A comparative clinical trial of Org GB 94 and imipramine in the treatment of depression in general practice. Journal of International Medical Research 1975;3:251‐80. [DOI] [PubMed] [Google Scholar]
- Murphy JE. Mianserin in the treatment of depressive illness and anxiety states in general practice. British Journal of Clinical Pharmacology 1978;5 Suppl 1:81‐5. [PMC free article] [PubMed] [Google Scholar]
Murphy 2000 {published data only}
- Murphy GM. Pharmacogenetics of mirtazapine and paroxetine in the treatment of geriatric major depression. 39th Annual Meeting of the American College of Neuropychopharmacology. San Juan, Puerto Rico, 2000.
Nair 1993 {published data only}
- Nair NPV, Amin M, Holm P, Katona C, Klitgaard N, Ng Ying Kin NM, et al. Moclebemide and nortriptyline in elderly depressed patients A randomised multicentre trial against placebo. Journal of Affective Disorders 1995;33:1‐9. [DOI] [PubMed] [Google Scholar]
- Ng Ying Kin NMK, Klitgaard N, Nair NP, Amin M, Kragh‐Sorensen P, Schwartz G, et al. Clinical relevance of serum nortritptyline and 10 hydroxy‐nortriptyline measurements in the depressed elderly:a multicenter pharmacokinetic and pharmacodynamic study. Neuropsychopharmacology 1996;15(1):1‐6. [DOI] [PubMed] [Google Scholar]
- Ng Ying Kin NMK, Nair NP, Amin M, Schwartz G, Kamalludin Ahmed S, Holm P, et al. The Dexamethasone suppression test and treatment outcome in elderly depressed patients participating in a placebo controlled multicenter trial involving Moclobemide and Nortriptyline. Biological Psychiatry 1997;42:925‐31. [DOI] [PubMed] [Google Scholar]
Newhouse 1988 {published data only}
- Newhouse PA, Sunderland T, Tariot PN, Weingartner H, Thompson K, Mellow AM, et al. The effects of acute Scopolamine in geriatric depression. Archives of General Psychiatry 1988;45(10):906‐12. [DOI] [PubMed] [Google Scholar]
Newhouse 1996 {published data only}
- Newhouse P, Ko G, Richter E. Comparison of Sertraline and Fluoxetine in depressed geriatric outpatients:Plasma levels and efficacy. Unknown 1996;P‐1‐4:35. [Google Scholar]
Nielsen 1993 {published data only}
- Nielsen BM, Behnke K, Arup P, Christiansen PE, Geisler A, Ipsen E, et al. A comparison of fluoxetine and imipramine in the treatment of outpatients with major depressive disorder. Acta Psychiatrica Scandinavica 1993;87(4):269‐72. [DOI] [PubMed] [Google Scholar]
Pancheri 1994 {published data only}
- Pancheri P, Delle Chiaie R, Donnini M, Seripa S, Gambino C, Vicario E, et al. Effects of Moclobemide on depressive symptoms and cognitive performance in a geriatric population:A controlled comparative study versus Imipramine. Clinical Neuropharmacology 1994;17 Suppl 1:S58‐73. [DOI] [PubMed] [Google Scholar]
Poldinger 1982b {published data only}
- Poldinger W. Double blind comparison of the antidepressives viloxazine and imipramine [Doppelblindvergleich der Antidepressiva Viloxazin und Imipramin]. Deutsche Medizinische Wochenschrift 1982;107(17):661‐5. [DOI] [PubMed] [Google Scholar]
Pollock 1998 {published data only}
- Pollock BG, Mulsant BH, Nebes R, Kirshner MA, Begley AE, Mazumdar S, et al. Serum anticholinergicity in elderly depressed patients treated with Paroxetine or Nortriptyline. American Journal of Psychiatry 1998;155(8):1110‐2. [DOI] [PubMed] [Google Scholar]
Rickels 1994c {published data only}
- Rickels K, Schweizer E, Clary C, Fox I, Weise C. Nefazodone and imipramine in major depression: a placebo‐controlled trial. British Journal of Psychiatry 1994;164:802‐5. [DOI] [PubMed] [Google Scholar]
- Zajecka JM. The effect of nefazodone on comorbid anxiety symptoms associated with depression: experience in family‐practice and psychiatric outpatient settings. Journal of Clinical Psychiatry 1996;57 Suppl 2:10‐4. [PubMed] [Google Scholar]
Robertson 1994 {published data only}
- Burns RA, Lock T, Edwards DR, Katona CL, Harrison DA, Robertson MM, et al. Predictors of response to amine‐specific antidepressants. Journal of Affective Disorders 1995;35(3):97‐106. [DOI] [PubMed] [Google Scholar]
- Katona CLE, Abou‐Saleh MT, Harrison DA, Nairac BA, Edwards DR, Lock T, et al. Placebo‐controlled trial of lithium augmentation of fluoxetine and lofepramine. British Journal of Psychiatry 1995;166:80‐6. [DOI] [PubMed] [Google Scholar]
- Lawrence KM, Katona CL, Abou‐Saleh MT, Robertson MM, Nairac BL, Edwards DR, et al. Platelet 5‐HT uptake sites, labelled with 3H paroxetine, in controls and depressed patients, before and after treatment with fluoxetine or lofepramine. Psychopharmacology 1994;115(1‐2):261‐4. [DOI] [PubMed] [Google Scholar]
- Robertson MM, Abou‐Saleh MT, Harrison DA, Nairac BL. A double‐blind controlled comparison of fluoxetine and lofepramine in major depressive illness. Journal of Psychopharmacology 1994;8(2):98‐103. [DOI] [PubMed] [Google Scholar]
Robinson 2000 {published data only}
- Robinson RG, Schultz SK, Castillo C, Kopel T, Kosier JT, Newman RM, et al. Nortriptyline versus fluoxetine in the treatment of depression and in short‐term recovery after stroke: a placebo‐controlled, double‐blind study. American Journal of Psychiatry 2000;157(3):351‐9. [DOI] [PubMed] [Google Scholar]
Roose 1987 {published data only}
- Roose SP, Glassman AH, Giardina EG, Johnson LL, Walsh BT, Bigger JT Jr. Cardiovascular effects of imipramine and bupropion in depressed patients with congestive heart failure. Journal of Clinical Psychopharmacology 1987;7(4):247‐51. [PubMed] [Google Scholar]
Roose 1994 {published data only}
- Roose SP, Glassman A H, Attia E, Woodring S. Comparative efficacy of selective Serotonin reuptake inhibitors and Tricyclics in the treatment of Melancholia. American Journal of Psychiatry 1994;151:1735‐9. [DOI] [PubMed] [Google Scholar]
Roose 1998 {published data only}
- Roose SP, Glassman AH, Attia E, Woodring S, Giardina EG, Bigger JT Jr. Cardiovascular effects of fluoxetine in depressed patients with heart disease. American Journal of Psychiatry 1998;155(5):660‐5. [DOI] [PubMed] [Google Scholar]
Rothblum 1982 {published data only}
- Rothblum ED, Sholomskas AJ, Berry C, Prusoff BA. Issues in clinical trials with the depressed elderly. Journal of the American Geriatrics Society 1982;30(11):694‐9. [DOI] [PubMed] [Google Scholar]
Sacchetti 1997 {published data only}
- Sacchetti E, Conte G, Guarneri L, Calzeroni A, Bertini M, Panariello A. Effectiveness of fluvoxamine and paroxetine in major depressives with psychotic features. Human Psychopharmacology 1997;12:277‐8. [Google Scholar]
Scarzella 1985 {published data only}
- Scarzella L, Scarzella R, Mailland F, Bergamasco B. Amineptine in the management of the depressive syndromes.. Progresses in Neuro‐Psychopharmachology and Biological Psychiatry 1985;9(4):429‐39. [DOI] [PubMed] [Google Scholar]
Schatzberg 2000 {published data only}
- Schatzberg AF, Kremer C, Rodrigues HE. Mirtazapine versus paroxetine in elderly depressed patients. 39th Annual Meeting of the American College of Neuropsychopharmacology; Dec 10‐14; San Juan; Puerto Rico. 2000.
Schifano 1990 {published data only}
- Schifano F, Garbin A, Renesto V, Dominicis MG, Trinciarelli G, Silvestri A, et al. A double blind comparison of mianserin and maprotiline in depressed medically ill elderly people. Acta Psychiatrica Scandinavica 1990;81:289‐94. [DOI] [PubMed] [Google Scholar]
Schiwy 1989a {published data only}
- Schiwy W, Heath WR, Delini Stula A. Therapeutic and side‐effect profile of a selective and reversible MAO‐A inhibitor, brofaromine Results of dose‐finding trials in depressed patients. Journal of Neural Transmission. Supplementum 1989;28:33‐44. [PubMed] [Google Scholar]
Schiwy 1989b {published data only}
- Schiwy W, Heath WR, Delini Stula A. Therapeutic and side‐effect profile of a selective and reversible MAO‐A inhibitor, brofaromine Results of dose‐finding trials in depressed patients. Journal of Neural Transmission. Supplementum 1989;28:33‐44. [PubMed] [Google Scholar]
Schneider 1998a {published data only}
- Schneider LS, Small GW, Clary CM. Estrogen replacement therapy status and antidepressant to sertraline. 151st Annual Meeting of the American Psychiatric Association. Toronto, Ontario, Canada. 30th May 4th June. 1998.
Schneider 1998b {published data only}
- Schneider L, Small G, Clary C. Does estrogen replacement therapy augment response to sertraline in depressed elderly women. XXIst Collegium Internationale Neuro Psychopharmacologicum, Glasgow, Scotland. 12th 16th July. 1998.
Schone 1994 {published data only}
- Geretsegger C, Bohmer F, Ludwig M. Paroxetine in the elderly depressed patient:randomized comparison with Fluoxetine of effeicacy,cognitive and behavioural effects. International Clinical Psychopharmacology 1994;9:25‐9. [PubMed] [Google Scholar]
- Schone W, Ludwig M. A double blind study of Paroxetine compared with Fluoxetine in geriatric patients with major depression. Journal of Clinical Psychopharmacology 1993;13 Suppl 2:34‐9. [DOI] [PubMed] [Google Scholar]
- Schone W, Ludwig M. Paroxetin in the treatment of Geriatric depressed patients ‐ a double blind comparison with Fluoxetine [Paroxetin in der depressionsbehandlung geriatrischer patienten ‐eine doppleblinde Vergleichsstudie mit Fluoxetin]. Fortschritte der Neurologie Psychiatrie 1994;62 Suppl 1:16‐8. [PubMed] [Google Scholar]
Stanley 1998 {published data only}
- Stanley N, Kimber S, Fairweather DB, Hindmarch I. Venlafaxine and dothiepin in depressed elderly patients: A comparison of efficacy and effects on cognition. 11th European College of Neuropsychopharmacology Congress. Paris, France. 31st October 4th November 1998. 1998:P.1.044.
Stewart 1968 {published data only}
- Stewart JA, Mitchell PH. A comparative trial of desipramine and nortriptyline in depression. British Journal of Psychiatry 1968;114(509):469‐71. [DOI] [PubMed] [Google Scholar]
Stoppe 1998 {published data only}
- Stoppe A, Forlenza OV, Hirata E, Ferreira RC, Almeida OP. Antidepressant Efficacy and Tolerability Comparison of Sertraline and Imipramine in Brazilian Elderly Outpatients. 151st Annual Meeting of the American Psychiatric Association. Toronto, Ontario, Canada. 30th May 4th June. 1998.
Strik 1998 {published data only}
- Strik J, Honig A, Lousberg R, Cheriex EC, van‐Praag HM. Cardiac side effects of two SSRI's in middle‐aged and elderly depressed patients. XXIst Collegium Internationale Neuro psychopharmacologicum, Glasgow, Scotland. 12th 16th July. 1998.
- Strik JJ, Honig A, Lousberg R, Cheriex EC, Praag HM. Cardiac side‐effects of two selective serotonin reuptake inhibitors in middle‐aged and elderly depressed patients. International Clinical Psychopharmacology 1998;13(6):263‐7. [DOI] [PubMed] [Google Scholar]
- Strik JJ, Lousberg R, Cheriex EC, Praag HM, Honig A. Cardiac side effects of two SSRIs in middle‐aged and elderly depressed patients. 152nd Annual Meeting of the American Psychiatric Association. Washington DC, USA. 15 20th May. 1999.
Taragano 1997 {published data only}
- Taragano FE, Lyketsos CG, Mangone CA, Allegri RF, Comesana‐Diaz E. A double‐blind, randomized, fixed‐dose trial of fluoxetine vs amitriptyline in the treatment of major depression complicating Alzheimer's disease. Psychosomatics 1997;38(3):246‐52. [DOI] [PubMed] [Google Scholar]
Thayssen 1981 {published data only}
- Thayssen P, Bjerre M, Kragh‐Sorensen P, Moller M, Petersen OL, Kristensen CB, et al. Cardiovascular effect of imipramine and nortriptyline in elderly patients. Psychopharmacology 1981;74(4):360‐4. [DOI] [PubMed] [Google Scholar]
Tourigny‐Rivard 1996 {published data only}
- Tourigny‐Rivard MF, Nair VK, Vincent P. Fluoxetine vs Desipramine in elderly depressed patients. Conference Abstract Only ‐ Xth World Congress of Psychiatry Madrid Spain. 1996.
Volz 1995 {published data only}
- Volz H P, Muller H, Moller H J. Are there any differences in the safety and efficacy of brofaromine and imipramine between non‐elderly and elderly patients with major depression?. Neuropsychobiology 1995;32(1):23‐30. [DOI] [PubMed] [Google Scholar]
Volz 1997a {published data only}
- Volz HP, Gleiter CH, Moller HJ. Brofaromine versus imipramine in in‐patients with major depression‐‐a controlled trial. Journal of Affective Disorders 1997;44(2‐3):91‐9. [DOI] [PubMed] [Google Scholar]
Von Bauer 1969 {published data only}
- Bauer G, Nowak H. Doxepin, a new antidepressant: comparison of effects with amitriptyline [Dexepin, ein neues Antidepressivum: Wirkungsvergleich mit Amitriptylin]. Arzneimittelforschung 1969;19(10):1642‐6. [PubMed] [Google Scholar]
Waite 1986 {published data only}
- Waite J, Grundy E, Arie T. A controlled trial of antidepressant medication in elderly in patients. International Clinical Psychopharmacology 1986;1:113‐26. [DOI] [PubMed] [Google Scholar]
Wakelin 1986 {published data only}
- Wakelin JS. Fluvoxamine in the treatment of the older depressed patient; double blind, placebo controlled data. International clinical psychopharmacology 1986;1:221‐30. [DOI] [PubMed] [Google Scholar]
Weber 2000 {published data only}
- Weber E, Stack J, Pollock BG, Mulsant B, Begley A, Mazumdar S ET AL. Weight change in older depressed patients during acute pharmacotherapy with paroxetine and nortriptyline: a double‐blind randomized trial. American Journal of Geriatric Psychiatry 2000;8(3):245‐50. [PubMed] [Google Scholar]
Weihls 2000 {published data only}
- Weihs KL, Settle EC, Batey SR, Houser TL, Donahue RM, Ascher JA. Buproprion sustained release versus paroxeting for the treatment of depression in the elderly. Journal of Clinical Psychiatry 2000;61(3):196‐202. [DOI] [PubMed] [Google Scholar]
Weissman 1992 {published data only}
- Weissman MM, Prusoff B, Sholomskas AJ, Greenald S. A double blind clinical trial of Alprazolam, Imipramine, or placebo in the depressed elderly. Journal of Clinical Psychpharmacology 1992;12:175‐82. [PubMed] [Google Scholar]
Wilkins 1989 {published data only}
- Wilkins JN, Spar JE, Carlson HE. Desipramine increases circulating growth hormone in elderly depressed patients:a pilot study. Psychoneuroendocrinology 1989;14(3):195‐202. [DOI] [PubMed] [Google Scholar]
Zapletalek 1990 {published data only}
- Zapletalek M, Faltus F, Svestka J, Molcan J, Binz U, Wendt G. Selective and reversible MAO‐inhibitor brofaromine compared with tranlycypromine [Der selektive und reversible MAO‐Hemmer Brofaromin im Vergleich zu Tranylcypromin]. Munchener Medizinische Wochenschrift 1990;132 Suppl 1:18‐20. [Google Scholar]
References to studies awaiting assessment
Branconnier 1981 {published data only}
- Branconnier RJ, Cole JO, Ghazvinian S. The therapeutic profile of mianserin in mild elderly depressives. Psychopharmacology Bulletin 1981;17(1):129‐31. [PubMed] [Google Scholar]
Doraiswamy 1998 {published data only}
- Doraiswamy PM, Krishnan KR, Clary C. Efficacy and safety of sertraline in depressed geriatric patients with vascular disease. 151st Annual Meeting of the American Psychiatric Association. Toronto, Ontario, Canada. 30th May 4th June. 1998.
Doraiswamy 2001b {published data only}
- Doraiswamy PM, Krishnan KR, Clary C. Does antidepressant therapy improve cognition in geriatric major depression? Evidence from two multicenter trials. 14th Annual Meeting of the American Association for Geriatric Psychiatry; 2001 23rd‐26th February, San Francisco, CA. 2001.
Dorn 1980 {published data only}
- Dorn M. Psychotropic drugs in medical practice. Double‐blind studies of lofepramine against amitriptyline [Psychopharmaka in der Praxis. Doppelblindprufung Lofepramin gegen Amitriptylin]. Zeitschrift fur Allgemeinmedizin 1980;56(2):133‐9. [PubMed] [Google Scholar]
Georgotas 1988 {published data only}
- Georgotas A, McCue RE, Cooper TB, Nagachandran N, Chang I. How effective and safe is continuation therapy in elderly depressed patients? Factors affecting relapse rate. Archives of General Psychiatry 1988;45(10):929‐32. [DOI] [PubMed] [Google Scholar]
Guelfi 1998 {published data only}
- Guelfi JD. Fluoxetine versus tianeptine in elderly depressed. 11th European College of Neuropsychopharmacology Congress. Paris, France. 31st October 4th November. 1998.
Karp 2001 {published data only}
- Karp J, Roose S, Sackeim H, Pesce V. Redefining remission in late‐life depression. 154th Annual Meeting of the American Psychiatric Association; 2001 May 5‐10; New Orleans; LA. 2001:NR192.
Katona 1996 {published data only}
Kretschmar 1979 {published data only}
- Kretschmar JH. Results of a double‐blind trial comparing mianserin and amitriptyline in elderly patients with depressive illness. Excerpta Medica 1979;ICS462:19‐25. [Google Scholar]
Roland 1992 {published data only}
- Roland A, Margakis P, Mullin J, Haug JO, Stordal E, Ekdal P, et al. Double‐blind, multicentre comparison of remergon and amitriptyline in elderly depressed patients. Clinical Neuropharmacology 1992;15(1 Pt B):182. [Google Scholar]
Schatzberg 2001 {published data only}
- Schatzberg AF, Cantillon M. Antidepressant early response and remission with venlafaxine and fluoxetine in geriatric outpatients. 14th Annual Meeting of the American Association for Geriatric Psychiatry; 2001 23rd‐26th February, San Francisco, CA. 2001.
Zhang 2001 {published data only}
- Zhang Z. Comparison of therapeutic effects of venlafaxine and fluoxetine in the treatment of senile depression. Shanghai Archives of Psychiatry 2001;14(2):97‐98. [Google Scholar]
Additional references
Alderson 2004
- Alderson P, Green S, Higgins JP. Assessment of study quality. Cochrane Reviewers’ Handbook 4.2.1 [updated December] Section 8. Chichester: John Wiley & Sons Ltd, 2004. [Google Scholar]
BMA 1999
- British Medical Association & Royal Pharmaceutical Society of Great Britain. British National Formulary. 8th Edition. London: BMA, 1999. [Google Scholar]
Feighner 1972
- Feighner JP, Robins E, Guze SB, Woodruff RA Jr, Winokur G, Munoz R. Diagnostic criteria for use in psychiatric research. Archives of General Psychiatry 1972;26:57‐63. [DOI] [PubMed] [Google Scholar]
Hamilton 1967
- Hamilton M. Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology 1967;6(4):278‐96. [DOI] [PubMed] [Google Scholar]
Katona 1994
- Katona C. Depression in old age. Chichester: John Wiley and Sons, 1994. [Google Scholar]
Montcrieff 2001
- Moncrieff J, Churchill R, Drummond C, McGuire H. Development of a quality assessment instrument for trials of treatment for depression and neurosis. International Journal of Methods in Psychiatric Research 2001;10(3):126‐33. [Google Scholar]
Montgomery 1979
- Mongomery SA, Asberg M. A new depression scale designed to be sensitive to change. British Journal of Psychiatry 1979;134:382‐9. [DOI] [PubMed] [Google Scholar]
Moskowitz 1986
- Moskowitz H, Burns M. Cognitive Performance in geriatric subjects after acute treatment with antidepressants. Neuropsychobiology 1986;15 Suppl 1:38‐43. [DOI] [PubMed] [Google Scholar]
Mulrow 1999
- Mulrow CD, Williams JW Jr, Trividi M, et al. Treatment of depression: Newer Pharmacotherapies. Evidence Report/Technology Assessment No 7. (Prepared by the San Antonio Evidence Based Practice Center based at The University of Texas Health Science Center at San Antonio under Contract 290‐97‐0012). San Antonio, TX: San Antonio Evidence Base Practice Center, February 1999. [Google Scholar]
Murphy 1982
- Murphy E. Social origins of depression in old age. British Journal of Psychiatry 1982;141:135‐42. [DOI] [PubMed] [Google Scholar]
Schneider 1995
- Schneider LS, Olin JT. Efficacy of acute treatment of geriatric depression. International Journal of Geriatric Psychiatry 1995;7 Suppl 7:7‐25. [DOI] [PubMed] [Google Scholar]
Williams 2000
- Williams J, Whitrow C, Chiquette E, Noel PH, Aguilar C, Cornell J. A systematic review of newer pharmacotherapies for depression in adults. Annals of Internal Medicine 2000;132(9):743‐56. [DOI] [PubMed] [Google Scholar]
Wilson 2005
- Wilson K, Mottram P, Sivananthan A, Nightingale A. Antidepressants versus placebo for the depressed elderly: Cochrane Review. The Cochrane Library 2005, Issue 2. [DOI] [PMC free article] [PubMed] [Google Scholar]
Woodhouse 1992
- Woodhouse K. The pharmacolog of major tranquillisers in the elderly. In: Katona C, Levey R editor(s). Depression and hallucinations in old age. London: Gaskle, 1992. [Google Scholar]
Zung 1965
- Zung WW. A self‐rating depression scale. Archives of General Psychiatry 1965;12:63‐70. [DOI] [PubMed] [Google Scholar]