Abstract
Introduction
Depression may affect up to 10% of the population, with symptoms recurring in half of affected people. In mild to moderate depression, there is no reliable evidence that any one treatment is superior in improving symptoms of depression, but the strength of evidence supporting different treatments varies.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of psychological treatments, and of interventions to reduce relapse rates, in mild to moderate or severe depression? What are the effects of psychological interventions to improve delivery of treatments in mild to moderate or severe depression? We searched: Medline, Embase, The Cochrane Library and other important databases up to April 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 55 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: befriending, care pathways, cognitive therapy, combining antidepressant drugs and psychological treatments, interpersonal psychotherapy, non-directive counselling, problem-solving therapy, relapse prevention programme.
Key Points
Depression may affect up to 10% of the population, with symptoms recurring in half of affected people.
In mild to moderate depression, there is no reliable evidence that any one treatment is superior in improving symptoms of depression, but the strength of evidence supporting different treatments varies.
Cognitive behavioural therapy and interpersonal psychotherapy reduce symptoms of mild to moderate depression, although many of the trials have been small.
Combining psychological treatment with antidepressant drugs may be more effective than either treatment alone.
Non-directive counselling may also be effective, but we don't know whether problem-solving therapy or befriending are beneficial.
Care pathways may improve the effectiveness of treatment for depression.
We don't know whether cognitive behavioural therapy or relapse prevention programmes are beneficial in reducing the risk of relapse after recovery.
About this condition
Definition
Depressive disorders are characterised by persistent low mood, loss of interest and enjoyment, and reduced energy. They often impair day to day functioning. Most of the RCTs assessed in this review classify depression using the Diagnostic and Statistical Manual of Mental Disorders IV (DSM)-IV or the International Classification of Mental and Behavioural Disorders 10 (ICD)-10. DSM-IV divides depression into major depressive disorder or dysthymic disorder. Major depressive disorder is characterised by one or more major depressive episodes (i.e. at least 2 weeks of depressed mood or loss of interest accompanied by at least 4 additional symptoms of depression). Dysthymic disorder is characterised by at least 2 years of depressed mood for more days than not, accompanied by additional symptoms that do not reach the criteria for major depressive disorder. ICD-10 divides depression into mild to moderate or severe depressive episodes. Mild to moderate depression is characterised by depressive symptoms and some functional impairment. Severe depression is characterised by additional agitation or psychomotor retardation with marked somatic symptoms. Treatment-resistant depression is defined as an absence of clinical response to treatment with a tricyclic antidepressant at a minimum dose of 150 mg daily of imipramine (or equivalent drug) for 4-6 weeks. In this review, we use both DSM-IV and ICD-10 classifications, but treatments are considered to have been assessed in severe depression if the RCT included inpatients. Older adults: Older adults are generally defined as people aged 65 years or older. However, some of the RCTs of older people in this review included people aged 55 years or over. The presentation of depression in older adults may be atypical: low mood may be masked, and anxiety or memory impairment may be the principal presenting symptoms. Dementia should be considered in the differential diagnosis of depression in older adults. Treating depressive disorders in adults: Depressive disorders are generally treated with a range of drug, physical, and psychological treatments. For coverage of drug and other physical treatments, see review on depression in adults: drug and physical treatments. Combined drug and psychological treatment and comparisons of psychological versus drug treatment are covered in this review. Population: This review does not cover intervention in women with postnatal depression (see review on postnatal depression), seasonal affective disorder, or depression because of a physical illness such as stroke or substance abuse.
Incidence/ Prevalence
Depressive disorders are common, with a prevalence of major depression between 5% and 10% of people seen in primary care settings. Two to three times as many people may have depressive symptoms but do not meet DSM-IV criteria for major depression. Women are affected twice as often as men. Depressive disorders are the fourth most important cause of disability worldwide, and are expected to become the second most important cause by 2020. Older adults: Between 10% and 15% of older people have depressive symptoms, although major depression is less common among older adults.
Aetiology/ Risk factors
The causes of depression are uncertain, but are thought to include both childhood events and current psychosocial adversity. Recent studies suggest that genetic factors may also be important, indicating that several chromosomal regions may be involved. However, phenotypes do not seem to exhibit classic Mendelian inheritance. Psychiatric research has also focused on the role that psychosocial factors, such as social context and personality dimensions, have in depression. Many theories emphasise the importance of temperament (differences in the adaptive systems), which can increase vulnerability to mood disturbances. Impairment in social relationships, gender, socioeconomic status, and dysfunctional cognition may also be involved. It seems that integrative models, which take into account the interaction of biological and social variables, offer the most reliable way to approach the complex causes of depression.
Prognosis
About half of people suffering a first episode of major depressive disorder experience further symptoms in the subsequent 10 years. Older adults: One systematic review (search date 1996, 12 prospective cohort studies, 1268 people, mean age 60 years) found that the prognosis may be especially poor in elderly people with a chronic or relapsing course of depression. Another systematic review (search date 1999, 23 prospective cohort studies in people aged 65 years or over, including 5 identified by the first review) found that depression in older people was associated with increased mortality (15 studies; pooled OR 1.73, 95% CI 1.53 to 1.95).
Aims of intervention
To improve mood, social and occupational functioning, and quality of life; to reduce morbidity and mortality; to prevent recurrence of depressive disorder; and to minimise adverse effects of treatment.
Outcomes
Depressive symptoms rated by the depressed person and clinician; social functioning; occupational functioning; quality of life; admission to hospital; rates of self harm; relapse of depressive symptoms; rates of adverse events. RCTs often use continuous scales to measure depressive symptoms (such as the Hamilton Depression Rating Scale [HAM-D], the Clinical Global Impression Scale [CGI], the Beck Depression Inventory [BDI], and the depression scale from the Hopkins Symptom Checklist). A reduction in score of 50% or more on these scales or a CGI score of 1 (very much improved) or 2 (much improved) is generally considered a clinically important response to treatment. Many RCTs express results in terms of effect size. Older adults: The HAM-D is not ideal for older people because it includes several somatic items that may be positive in older people who are not depressed. It has been the most widely used scale, although specific scales for elderly people (such as the Geriatric Depression Scale [GDS]) avoid somatic items.
Methods
BMJ Clinical Evidence search and appraisal April 2006. The following databases were used to identify studies for this review: Medline 1966 to April 2006, Embase 1980 to April 2006, Psychinfo 1980 to April 2006, and The Cochrane Library and Cochrane Central Register of Controlled Clinical Trials Issue 1, 2006. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (NICE). Abstracts of the studies retrieved were assessed independently by two information specialists using predetermined criteria to evaluate relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, at least single blinded, and containing more than 20 individuals of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. We also did a search for cohort studies on specific harms of named interventions. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the review as required. In this review, studies are included under the heading older adults if they specifically included people aged over 55 years. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).
Table.
GRADE evaluation of interventions for depression in adults: psychological treatments and care pathways
Important outcomes | Symptom severity, treatment success rates, relapse, social functioning, occupational functioning, quality of life, admission to hospital, self-harm, adverse effects | ||||||||
Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
What are the effects of psychological treatments in mild to moderate or severe depression? | |||||||||
49 RCTs (2885) | Symptom severity | Cognitive therapy v placebo/ other treatments | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for uncertainty about generalisability of results (different populations and different types of psychotherapies compared) |
4 (?) | Symptom severity | Cognitive/behavioural therapy v no treatment (in older adults) | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for uncertainty about generalisability of results |
37 (3166) | Treatment success | Psychotherapies v control/usual care | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for uncertainty about generalisability of results (different types and combinations of psychotherapies compared) |
28 (2000) | Treatment success | Cognitive therapy v other psychological treatments | 4 | –1 | –1 | –1 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results. Directness point deducted for uncertainty about generalisability of results (different populations and different types and combinations of psychotherapies compared) |
2 (409)Ref = 14, 25 | Treatment success | Interpersonal psychotherapy for initial treatment v usual care/no treatment | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
12 (857) | Symptom severity | Interpersonal psychotherapy for initial treatment v placebo/cognitive behavioural therapy | 4 | 0 | 0 | 0 | 0 | High | |
At least 3 RCTs (at least 204 people) | Treatment success | Interpersonal psychotherapy v cognitive behaviour therapy/antidepressants | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
3 (?) | Treatment success | Interpersonal psychotherapy v no treatment (in older adults) | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for incomplete reporting of data. Directness point deducted for unclear measurement of outcomes |
16 RCTs and 17 studies (at least 1842 people) | Symptom severity | Combination of psychological treatments and antidepressant drugs v either treatment alone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
2 (915)[ | Treatment success | Combination of psychological treatments and antidepressant drugs v either treatment alone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for no intention to treat analysis |
1 (102) | Symptom severity | Combining psychological treatments and antidepressant drugs for initial treatment v treatments alone (in older adults) | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
11 (1554) | Symptom severity | Non-directive counselling for initial treatment v usual care/no treatment | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for inclusion of other conditions |
1 (86) | Treatment success | Befriending v waiting list control | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for uncertainty about benefit |
3 (891) | Treatment success | Problem-solving therapy v placebo/control | 4 | –1 | –1 | –1 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for different results at different endpoints. Directness point deducted for unclear measurement of outcome |
2 (317) | Symptom severity | Problem-solving therapy provided by community mental health nurses v usual care from a GP | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for different results at different endpoints. Directness points deducted for unclear measurement of outcome and inclusion of other disorders |
1 (415) | Symptom severity | Problem-solving treatment v placebo (in older adults) | 4 | 0 | 0 | 0 | 0 | High | |
1 (232) | Treatment success | Problem-solving treatment v placebo (in older adults) | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
What are the effects of psychological interventions to reduce relapse rates in mild to moderate or severe depression? | |||||||||
at least 5 RCTs (694) | Relapse rates | Cognitive therapy v antidepressant drugs or usual clinical management | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for incomplete reporting of results and no long term results. Consistency point deducted for conflicting results |
1 (386) | Symptom severity | Relapse prevention programme v usual care | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
1 (386) | Relapse rates | Relapse prevention programme v usual care | 4 | 0 | 0 | 0 | 0 | High | |
What are the effects of psychological interventions to improve delivery of treatments in mild to moderate or severe depression? | |||||||||
24 (9399) | Symptom severity | Care pathways v usual care | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for analysis flaws. Directness point deducted for too many comparators |
1 (267) | Relapse rates | Recurrence prevention programmes v usual care/other interventions | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
5 (2383) | Treatment success | Care pathways v usual care | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for too many comparators |
5 (2261) | Symptom severity | Care pathways v usual care (in older adults) | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for too many comparators |
1 (138) | Treatment success | Care pathways v usual care (in older adults) | 4 | –1 | 0 | 0 | +1 | High | Quality point deducted for sparse data. Effect size point added for odds ratio greater than 2 |
Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion. Consistency: similarity of results across studies Directness: generaliseability of population or outcomes Effect size: based on relative risk or odds ratio
Glossary
- Active follow up
involves intensive follow up to assess adherence to the prescribed treatment, whether symptoms are improving, and whether any adverse effects are tolerable. Brief depression scales such as the Patient Health Questionnaire-9 (PHQ-9) may be used, which include details of depression symptom scores, and early warning signs of depression. Asking about adherence to antidepressant medication is also important. Alternatively, follow up may be face to face, or by telephone.
- Active response to results of follow up
involves proactively adjusting the treatment plan if a person with depression is not improving, is not adhering to treatment, or is having intolerable adverse effects. These adjustments may include changing the medicine or its dose, adding another form of treatment, or obtaining a specialist psychiatric opinion.
- Befriending
involves a person who is not depressed meeting the person with depression to talk and socialise for at least 1 hour a week, acting as a friend.
- Brief, non-directive counselling
Helping people to express feelings and clarify thoughts and difficulties; therapists suggest alternative understandings and do not give direct advice but try to encourage people to solve their own problems.
- Care pathway
A care pathway is a multidisciplinary plan of anticipated care.
- Case management
involves assigning a care manager to each person with depression, who co-ordinates the package of augmented care. The care manager may be a medical staff member, a practice nurse, a clinical psychologist, or a graduate mental health worker.
- Cognitive behavioural therapy
Brief (6–20 sessions over 12–16 weeks) structured treatment, incorporating elements of cognitive therapy and behavioural therapy. Behavioural therapy is based on learning theory and concentrates on changing behaviour. It requires a highly trained therapist.
- Cognitive therapy
Brief (20 sessions over 12–16 weeks) structured treatment aimed at changing the dysfunctional beliefs and negative automatic thoughts that characterise depressive disorders. It requires a highly trained therapist.
- Dysthymic disorder
Characterised by at least 2 years of depressed mood for more days than not, accompanied by additional symptoms that do not reach the criteria for major depressive disorder.
- Effect size
This expresses the degree of overlap between the range of scores in the control and experimental groups. The effect size can be used to estimate the proportion of people in the control group who had a poorer outcome than the average person in the experimental group; a proportion of 50% or less indicates that the treatment has no effect.
- High-quality evidence
Further research is very unlikely to change our confidence in the estimate of effect.
- Interpersonal psychotherapy
Standardised form of individual brief psychotherapy (usually 12–16 weekly sessions) primarily intended for outpatients with unipolar depressive disorders without psychotic features. It focuses on improving the person's interpersonal functioning and identifying the problems associated with the onset of the depressive episode.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Major depressive disorder
Characterised by one or more major depressive episodes (i.e. at least 2 weeks of depressed mood or loss of interest accompanied by at least 4 additional symptoms of depression).
- Mild to moderate depression
Characterised by depressive symptoms and some functional impairment.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Problem solving therapy
Consists of three stages: (1) identifying the main problems for the person, (2) generating solutions, and (3) trying out the solutions. Potentially briefer and simpler than cognitive therapy and may be feasible in primary care.
- Psychodynamic supportive psychotherapy
Aims to facilitate change by detecting and resolving underlying psychological conflicts. The treatment aims to be less challenging by incorporating supportive elements.
- Severe depression
Characterised by agitation or psychomotor retardation in addition to depressive symptoms and functional impairment with marked somatic symptoms. Treatments are considered to have been assessed in severe depression if the RCT included inpatients.
- Use of patient centred, motivational approaches
involves encouraging people to actively participate in their own care. Booklets or videos may be made available for patients and carers, which deliver information about the illness, its prognosis, its treatment, and simple cognitive and behavioural self treatment approaches. One or more professionals may deliver group teaching sessions on depression and how to recover.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Depression in adults: drug and physical treatments
Postnatal depression
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Dr Jonathan Price, University of Oxford, Oxford, UK.
Dr Rob Butler, University of Auckland and Waitemata Health, Auckland, New Zealand.
Dr Simon Hatcher, University of Auckland, Auckland, New Zealand.
Dr Michael Von Korff, Center for Health Studies, Seattle, USA.
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