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BMJ Clinical Evidence logoLink to BMJ Clinical Evidence
. 2009 Sep 3;2009:1004.

Obsessive compulsive disorder

G Mustafa Soomro 1
PMCID: PMC2907809

Abstract

Introduction

Obsessions or compulsions that cause personal distress or social dysfunction affect about 1% of adult men and 1.5% of adult women. About half of adults with obsessive compulsive disorder (OCD) have an episodic course, whereas the other half have continuous problems. Prevalence in children and adolescents is 2.7%. The disorder persists in about 40% of children and adolescents at mean follow-up of 5.7 years.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of initial treatments for obsessive compulsive disorder in adults? What are the effects of initial treatments for obsessive compulsive disorder in children and adolescents? What are the effects of maintenance treatment for obsessive compulsive disorder in adults? What are the effects of maintenance treatment for obsessive compulsive disorder in children and adolescents? What are the effects of treatments for obsessive compulsive disorder in adults who have not responded to initial treatment with serotonin reuptake inhibitors (SRIs)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (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 70 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: addition of antipsychotics to serotonin reuptake inhibitors; behavioural therapy alone or with serotonin reuptake inhibitors; cognitive therapy or cognitive behavioural therapy (CBT) (alone or with serotonin reuptake inhibitors); electroconvulsive therapy; serotonin reuptake inhibitors (citalopram, clomipramine, fluoxetine, fluvoxamine, paroxetine, or sertraline); and optimum duration of maintenance treatment.

Key Points

Obsessions or compulsions that cause personal distress or social dysfunction affect about 1% of adult men and 1.5% of adult women. Prevalence in children and adolescents is 2.7%.

  • About half of adults with obsessive compulsive disorder (OCD) have an episodic course, whereas the other half have continuous problems. Up to half of adults show improvement of symptoms over time. The disorder persists in about 40% of children and adolescents at mean follow-up of 5.7 years.

In adults,CBT and behavioural therapy improve symptoms of OCD compared with a waiting list control.

  • Behavioural therapy may be as effective at improving symptoms as CBT, but we don't know how they compare with SRIs (SSRIs and clomipramine). Behavioural therapy may be more effective than relaxation.

SRIs improve symptoms of OCD in adults compared with placebo. Abrupt withdrawal of SRIs is associated with adverse effects.

  • SRIs seem more effective at reducing symptoms compared with other antidepressants, including tricyclic antidepressants (other than clomipramine) or MAOIs.

  • We don't know whether SRIs are more effective than venlafaxine.

We don't know whether combining SRIs and cognitive therapy or behavioural therapy improves symptoms compared with each treatment alone.

We don't know whether electroconvulsive therapy improves symptoms in adults with OCD.

In children and adolescents, CBT and SRIs improve symptoms of OCD. We don't know whether CBT in combination with SRIs is more effective than CBT alone, but it may be more effective than SRIs alone.

We don't know whether behavioural therapy improves symptoms in children and adolescents with OCD.

We don't know which is the most effective SRI to use, or for how long maintenance treatment should continue in adults or children and adolescents.

Adding antipsychotic drugs to SRIs may improve symptoms in adults who did not respond to SRIs alone, although RCTs have given conflicting results.

CAUTION: SSRIs have been associated with an increase in suicidal ideation in children and adolescents.

About this condition

Definition

Obsessive compulsive disorder (OCD) involves obsessions, compulsions, or both, that are not caused by drugs or by a physical disorder, and which cause significant personal distress or social dysfunction. The disorder may have a chronic or an episodic course. Obsessions are recurrent and persistent ideas, images, or impulses that cause pronounced anxiety, and that the person perceives to be self-produced. Compulsions are repetitive behaviours or mental acts performed in response to obsessions or according to certain rules, which are aimed at reducing distress or preventing certain imagined dreaded events. People with OCD may have insight into their condition, in that obsessions and compulsions are usually recognised and resisted. There are minor differences in the criteria for OCD between the DSM-III, DSM-III-R, and DSM-IV and the ICD-10.

Incidence/ Prevalence

In adults: One national, community-based survey of OCD in the UK (1993, 10,000 people) found that 1.0% of men and 1.5% of women reported symptoms in the previous month. A survey of a random sample of people living in private households in the UK (2000, 8580 adults aged 16-74 years) found that 1.1% of those surveyed reported symptoms of OCD during the previous week. An epidemiological catchment area survey carried out in the USA in 1984 (about 10,000 people) found an age- and sex-standardised annual prevalence of OCD in people aged 26 to 64 years of 1.3%, and a lifetime prevalence of 2.3%. Subsequent national surveys used a similar methodology to the survey in the USA, and found broadly similar age- and sex-standardised annual and lifetime prevalence rates in Canada, Puerto Rico, Germany, Korea, and New Zealand, but a slightly lower prevalence in Taiwan (see table 1 ). In children and adolescents: Prevalence in children and adolescents was 2.7% in the USA in a community study conducted by the National Institute of Mental Health (NIMH) Methods for Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. The study evaluated a community sample of 1285 caregiver-child pairs, where both members of the pair were interviewed using structured interview DISC 2.3 with DSM-III-R criteria.

Table 1.

National surveys of age- and sex-standardised annual and lifetime prevalence of OCD in adults aged 26–64 years.

Country Survey size (adults) Annual prevalence Lifetime prevalence
Canada 2200 1.4% 2.3%
Puerto Rico 1200 1.8% 2.5%
Germany 4811 1.6% 2.1%
Taiwan 7400 0.4% 0.7%
Korea 4000 1.1% 1.9%
New Zealand 1200 1.1% 2.2%

Aetiology/ Risk factors

The cause of OCD is uncertain. In adults: Behavioural, cognitive, genetic, and neurobiological factors have been implicated. Limited evidence from genetic studies in families, and in twins, suggests that genetic factors may be involved, at least in some groups. Risk factors include a family history of OCD, being single (which could be a consequence of the disorder), and belonging to a higher socioeconomic class. The risk of OCD in women is higher than in men in most countries. Other risk factors include cocaine abuse, not being in paid employment, past history of alcohol dependence, affective disorder, and phobic disorder. In children and adolescents: About half of children and adolescents displayed "micro-episodes of OCD" characterised by excessive rigidity and repetitive rituals some years before developing the disorder. Tics in childhood also predicted an increase in OCD symptoms in late adolescence.

Prognosis

In adults: One study (144 people followed for a mean of 47 years) found that an episodic course of OCD was more common during the initial years of the disease (about 1-9 years), but that a chronic course was more common afterwards. Over time, the study found that 39% to 48% of people had symptomatic improvement. A 1-year prospective cohort study found that 46% of people had an episodic course and 54% had a chronic course. In children and adolescents: A systematic review (search date not reported; 22 studies with mean follow-up period of 5.7 years) examining the course of OCD in children and adolescents (mean age of onset 10.4 years; mean study entry age 13.3 years) found that the rate of persistent, full OCD was 41% and the rate of persistent, full, or subclinical OCD was 60%. Greater persistence was predicted by early onset of the disorder, increased OCD duration, and history of inpatient status.

Aims of intervention

To improve symptoms, and to reduce the impact of illness on social functioning and quality of life, with minimal adverse effects of treatment.

Outcomes

Severity of symptoms; social functioning; and adverse effects of treatment. Commonly used instruments for measuring symptoms include: the Hamilton Anxiety Rating Scale; the Hamilton Depression Rating Scale; the Yale-Brown Obsessive Compulsive Scale (YBOCS); and the children's version of the YBOCS.

Methods

Clinical Evidence search and appraisal August 2007. The following databases were used to identify studies for this systematic review: Medline 1966 to June 2007, Embase 1980 to August 2007, Psychinfo 1967 to August 2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials, 2007, Issue 3. 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 NICE. We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using pre-determined criteria to identify 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 use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. For the purpose of this review, trials mainly including people aged 16 years and above are included in the adult sections, and trials mainly including people aged under 18 years are included in the children and adolescent sections. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). 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 obsessive compulsive disorder in adults or in children and adolescents

Important outcomes Symptom improvement, relapse rate, quality of life, adverse effects
Number of studies (participants) Outcome Comparison Type of evidence Quality Consistency Directness Effect size GRADE Comment
What are the effects of initial treatments for obsessive compulsive disorder in adults?
3 (72) Symptom improvement Behavioural therapy v waiting list control 4 –2 0 0 0 Low Quality points deducted for sparse data and no intention-to-treat analysis
2 (339) Symptom improvement Behavioural therapy v relaxation 4 –2 0 0 0 Low Quality points deducted for incomplete reporting of results and no intention-to-treat analysis
8 (280) Symptom improvement Behavioural therapy v cognitive therapy or CBT 4 –2 –1 0 0 Very low Quality points deducted for no intention-to-treat analysis and incomplete reporting of results. Consistency point deducted for different results for different outcomes
2 (39) Symptom improvement Cognitive therapy v waiting list control 4 –1 0 –2 0 Very low Quality point deducted for sparse data. Directness points deducted for restricted population in one RCT and different time points assessed in intervention and comparison groups
5 (130) Symptom improvement CBT v waiting list control 4 –2 0 0 0 Low Quality points deducted for sparse data and for quasi-randomisation of one RCT
1(43) Quality of life CBT v waiting list control 4 –2 0 0 0 Low Quality points deducted for sparse data and incomplete reporting of results
At least 16 (at least 2356 people) Symptom improvement SRIs v placebo 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 inclusion of children
At least 11 RCTs (at least 1240 people) Symptom improvement SRIs v each other 4 –1 0 –1 0 Low Quality point deducted for incomplete reporting. Directness point deducted for low dose of clomipramine used in one RCT
2 (215) Symptom improvement SRIs v venlafaxine 4 –1 0 –1 0 Low Quality point deducted for no intention-to-treat analysis. Directness point deducted for small number of comparators
9 (365) Symptom improvement SRIs v tricyclic antidepressants other than clomipramine and MAOIs 4 –1 0 –2 0 Very low Quality point deducted for unclear outcome assessment.Directness points deducted for inclusion of children in one RCT and population restricted to people with OCD and major depressive disorder in another RCT and combined comparison group v single agent
1(56) Symptom improvement SRIs v CBT 4 –1 –1 0 0 Low Quality point deducted for sparse data. Consistency point deducted for different results for different outcomes
1(56) Quality of life SRIs v CBT 4 –1 0 0 0 Moderate Quality point deducted for sparse data
2 (148) Symptom improvement Behavioural or cognitive therapy plus SRI v BT/CT alone or plus placebo 4 –2 –1 0 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for different results between studies
1 (96) Symptom improvement Behavioural or cognitive therapy plus SRI v SRI alone 4 –2 –1 –1 0 Very low Quality points deducted for sparse data and no intention-to-treat analysis. Consistency point deducted for different results for different outcomes. Directness points deducted for inclusion of venlafaxine and for population restricted to people who previously responded to drug treatment
What are the effects of initial treatments for obsessive compulsive disorder in children and adolescents?
2 (133) Symptom improvement CBT v waiting list control or placebo 4 –2 0 –1 0 Very low Quality points deducted for sparse data and quasi-randomisation of one RCT. Directness point deducted for different study points
3 (118) Symptom improvement CBT v SRIs 4 –2 0 –1 0 Very low Quality points deducted for sparse data and unclear randomisation. Directness point deducted for no statistical comparison between groups
1 (40) Symptom improvement Different types of CBT v each other 4 –1 0 –1 0 Low Quality points deducted for sparse data. Directness point deducted for use of co-intervention
12 (at least 933) Symptom improvement SRIs v placebo 4 –1 –1 –1 0 Very low Quality point deducted for incomplete reporting of results. Consistency point deducted for different outcome measures used. Directness point deducted for inclusion of non-SRI antidepressants
1 (56) Symptom improvement CBT plus SRIs v placebo 4 –2 0 0 0 Low Quality points deducted for sparse data and incomplete reporting of results
2 (76) Symptom improvement CBT plus SRIs v SRIs alone 4 –3 0 0 0 Very low Quality points deducted for sparse data, weak methods (not reporting method of randomisation or blinding) and incomplete reporting of results
1 (56) Symptom improvement CBT plus SRIs v CBT alone 4 –2 0 0 0 Low Quality points deducted for sparse data and incomplete reporting of results
What are the effects of maintenance treatment for obsessive compulsive disorder in adults?
3 (397) Relapse rates Ongoing SRIs v no ongoing treatment/placebo 4 0 –1 –2 0 Very low Consistency point deducted for different results for different outcomes. Directness points deducted for differences in regimens between studies and use of composite outcome in one RCT
What are the effects of treatments for obsessive compulsive disorder in adults who have not responded to initial treatment with serotonin reuptake inhibitors?
10 (305) Symptom improvement Adding antipsychotics to SRIs versus adding placebo to SRIs 4 –1 –1 –1 0 Very low Quality point deducted for weak methods (unclear method of randomisation). Consistency point deducted for conflicting results. Directness point deducted for inclusion of non-SSRI antidepressants

Type of evidence: 4 = RCT Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio

Glossary

Behavioural therapy

Consists of exposure to the anxiety-provoking stimuli, and prevention of ritualistic behaviour (engaging in compulsions).

CBT

This is a composite therapy that combines techniques from cognitive therapy and behavioural therapy.

Chronic OCD

Continuous course without periods of remission since first onset.

Clinical Global Impression Scale

is a one-item, observer-rated scale for measuring the severity of a condition. It has been investigated for validity and reliability. It is scored on a scale from 0 (not ill at all) to 7 (severely ill).

Cognitive restructuring

An intervention that involves asking questions to help people challenge the stereotyped and repetitive thoughts and images that enhance fear.

Cognitive therapy

Aims to correct distorted thoughts (such as exaggerated sense of harm and personal responsibility) by Socratic questioning, logical reasoning, and hypothesis testing.

Episodic OCD

Episodic course with periods of remission since first onset.

Exposure homework

Tasks involving contact with anxiety provoking situations to be carried out outside regular psychotherapy sessions.

Hamilton Anxiety Rating Scale

is a 14-item observer-rated scale for measuring the severity of anxiety. It has been investigated for validity and reliability. Each item is rated on a 5-point scale from 0 (no symptoms) to 4 (severe or grossly disabling symptoms). Total score ranges from 0 to 56, with 14 or higher indicating clinically significant anxiety.

Hamilton Depression Rating Scale

is a 21-item observer-rated scale for measuring the severity of depression. Hamilton recommended that the first 17 items only be used for this purpose, as the last four items do not measure the severity of depression. It has been investigated for validity and reliability. Items are measured on a scale of 0–4 or 0–2 (with a higher score indicating more severe symptoms). Total score ranges from 0 to 50, with a score of 8 or above indicating clinically significant depression.

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.

Maudsley Obsessional Compulsive Inventory

is a 30-item self-report true–false scale, designed to measure the total frequency of OCD symptoms. Although the internal consistency, test–retest reliability, and validity are satisfactory, the scale is relatively insensitive to changes in symptoms.

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.

Schizotypal personality disorder

Characterised by discomfort in close relationships, cognitive and perceptual distortions, and eccentric behaviour.

Tic disorder

Characterised by motor tics, vocal tics, or both.

Very low-quality evidence

Any estimate of effect is very uncertain.

Yale–Brown Obsessive Compulsive Scale (YBOCS)

is a validated, observer-rated scale for measuring symptom scores. It rates the severity of both obsessions and compulsions across five dimensions (time spent, interference with functioning, distress, resistance, and control), each on a 5-point scale from 0 (the dimension is absent) to 4 (dimension is present to an extremely severe degree). The total score range of obsessions and compulsions combined is 0–40 (the higher the score, the more severe the condition). Most trials use a 25% or 35% reduction in YBOCS scores from baseline as indicative of clinically important improvement.

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.

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BMJ Clin Evid. 2009 Sep 3;2009:1004.

Behavioural therapy in adults

Summary

SYMPTOM IMPROVEMENT Compared with waiting list control: Behavioural therapy may be more effective at improving symptoms (assessed using Yale–Brown Obsessive Compulsive Scale) in adults with OCD (low-quality evidence). Compared with relaxation: Behavioural therapy may be more effective at improving symptoms in adults with OCD (low-quality evidence). Compared with cognitive therapy or CBT: We don't know how behavioural therapy compares with cognitive therapy or CBT for improving symptoms in adults with OCD (very low-quality evidence). NOTE We found no clinically important results from RCTs about behavioural therapy compared with SRIs in adults with OCD.

Benefits

Behavioural therapy versus waiting list control:

We found one systematic review (search date 2006; 3 RCTs; 72 adults aged 16–65 years with DSM-IV or DSM-III-R OCD) comparing behavioural therapy versus waiting list control. It found that behavioural therapy significantly improved OCD symptoms over 6–16 weeks of treatment assessed using the Yale–Brown Obsessive Compulsive Scale (YBOCS) compared with waiting list control (YBOCS: WMD –11.73, 95% CI –14.52 to –8.95). Behavioural therapy involved exposure prevention therapy in two identified studies, and exposure prevention therapy plus relaxation in the third identified study. The analyses in two of the identified RCTs were not by intention to treat (ITT).

Behavioural therapy versus relaxation:

We found two systematic reviews (search dates 1995, 2007). The first review (2 RCTs; 121 adults aged 19–40 years) found that behavioural therapy significantly improved symptoms over 4–16 weeks of treatment compared with relaxation (standardised mean differences 1.18; CI not reported; P < 0.01). The second review did not pool data, and only one of the identified RCTs met Clinical Evidence inclusion criteria for reporting. The identified RCT (218 people aged 15–80 years [mean age 39 years] with DSM-IV OCD, 49% of whom were also taking an SRI) compared three treatments: behavioural therapy guided by a computer, behavioural therapy guided by a clinician, and relaxation. It found that both types of behavioural therapy significantly improved obsessive-compulsive symptoms, and self-rated occupational and social functioning after 10 weeks of treatment compared with relaxation (YBOCS: mean reduction: –5.6 with computer-guided behavioural therapy v –8.0 with clinician-guided behavioural therapy v –1.7 with relaxation; P < 0.001 for relaxation v either type of behavioural therapy; work and social adjustment scale [scale not defined; improvement in scale favourable]: mean improvement from baseline: 5.1 with computer-guided behavioural therapy v 6.8 with clinician-guided behavioural therapy v 2.0 with relaxation; P = 0.032 for relaxation v computer-guided behavioural therapy; P = 0.001 for relaxation v clinician-guided behavioural therapy; analysis not by ITT).

Behavioural therapy versus cognitive therapy or CBT:

We found one systematic review and four subsequent RCTs. The systematic review (search date 1995; 4 RCTs; 92 adults aged 19–40 years) found no significant difference in symptoms over 4–16 weeks between behavioural therapy and cognitive therapy (SMD –0.19; reported as P > 0.05; no further data reported).

The first subsequent RCT (76 adults aged 18–56 years) found no significant difference between group behavioural therapy (exposure with response prevention) and group CBT in recovery (defined as a 6-point YBOCS score reduction and score of 12 or less) immediately after 12 weeks of treatment (12/32 [38%] with behavioural therapy v 5/31 [16%] with CBT; P = 0.09). However, it found that behavioural therapy significantly improved recovery at 3 months' follow-up compared with CBT (AR: 14/31 [45%] with behavioural therapy v 4/31 [13%] with CBT; P = 0.01; analysis not by ITT).The second subsequent RCT (63 adults aged 18–65 years) found no significant difference between behavioural therapy and cognitive therapy in the proportion of people achieving at least 25% improvement in YBOCS score after 16 weeks of treatment (absolute numbers not reported; OR 0.7, 95% CI 0.2 to 2.0).The third subsequent RCT compared 12 sessions of behavioural therapy versus 12 sessions of cognitive therapy. It found that, after treatment, cognitive therapy significantly improved OCD behaviours (assessed using the Maudsley Obsessional Compulsive Inventory) compared with behavioural therapy, but found no significant difference between treatments on the YBOCS score (22 adults aged 19–68 years with DSM-III-R diagnosis of OCD; 18 completed treatment; results presented graphically; P = 0.006 for the Maudsley Inventory; P = 0.022 for YBOCS; not significant after adjusting for multiple outcome measures). The fourth subsequent RCT (54 adults [mean age 38.3 years] with DSM-IV OCD) compared 20 weekly sessions of: an inference-based approach (16 adults); a cognitive appraisal model (16 adults); and exposure and response prevention (12 adults). The inference-based approach consisted of challenging the primary reasoning (inference) about the obsession (e.g., the door knob is contaminated); the cognitive appraisal model (same as cognitive therapy) used education in normalisation of the primary inference, then subsequently challenged the exaggerated appraisals of such inference; and exposure and response prevention consisted of standard exposure and response prevention. The RCT found no significant difference among groups in the YBOCS score (YBOCS score pre-intervention to post-intervention: 19.2 to 10.4 with exposure and response prevention v 25.5 to 13.3 with cognitive appraisal model v 25.3 to 13.1 with inference-based approach; between-group P = 0.51). The results were based on 44/54 (81%) adults who completed 20 weeks' treatment, and the analysis was not by intention to treat.

Behavioural therapy versus SRIs:

See benefits of SRIs in adults.

Harms

Case reports have described unbearable and unacceptable anxiety in some people receiving behavioural therapy.

Behavioural therapy versus waiting list control:

The review gave no information on adverse effects of behavioural therapy. There was no significant difference in the proportion of adults who withdrew from behavioural therapy compared with waiting list control (13/52 [25%] with behavioural therapy v 6/35 [17%] with waiting list control; OR 1.66, 95% CI 0.57 to 4.86). One RCT (3-arm study comparing CBT v behavioural therapy plus relaxation v waiting list control) identified by the review reported that some people experienced an increase in co-morbid symptoms (panic, depression, or substance misuse) during treatment, and many of these people withdrew (actual numbers and treatment groups not reported). One person receiving behavioural therapy plus relaxation became increasingly suicidal and was removed from the study.

Behavioural therapy versus relaxation:

The reviews and RCT gave no information on adverse effects of behavioural therapy or relaxation.

Behavioural therapy versus cognitive therapy or CBT:

The review gave no information on adverse effects of behavioural therapy or CBT.The first, second, and fourth subsequent RCT did not report on adverse effects. The third subsequent RCT found that three people (3/11 [27%]) withdrew from behavioural therapy and one person (1/10 [10%]) withdrew from cognitive therapy.

Behavioural therapy versus SRIs:

See harms of SRIs in adults.

Comment

Factors predicting outcome:

We found two RCTs of behavioural therapy (total 96 adults [mean ages 35 and 33 years]; duration 2.5 months and 32 weeks) and two retrospective cohort studies (total 346 adults [mean ages 36 and 34 years]; duration 1 year and 11 weeks), which assessed factors predicting outcome. These found that poorer outcome was predicted by initial severity, depression, longer duration, poorer motivation, and dissatisfaction with the therapeutic relationship. Good outcome was predicted by early adherence to exposure homework, employment, living with one's family, no previous treatment, having fear of contamination, overt ritualistic behaviour, and absence of depression. Good outcome for women was predicted by having a co-therapist (someone, usually related to the person concerned, who is enlisted to help with treatment outside regular treatment sessions).

Maintenance of improvement:

A prospective follow-up (20 adults [mean age 35 years] with OCD; specific diagnostic criteria not reported) after a 6-month RCT of behavioural therapy found that 79% maintained improvement in OCD symptoms at 2 years of follow-up. A prospective non-inception cohort study of behavioural therapy in 21 adults (aged 18–58 years) with OCD (specific diagnostic criteria not reported) found that, after 2 weeks of treatment, 68% to 79% maintained complete or much improvement in symptoms at 3 months of follow-up. In both studies, some people received additional behavioural therapy during follow-up.

Substantive changes

Behavioural therapy in adults Two systematic reviews added. One review found that behavioural therapy significantly improved OCD symptoms over 6–16 weeks of treatment compared with waiting list control. One review identified one previously included RCT, satisfying Clinical Evidence inclusion criteria. No new data added. Categorisation changed from Beneficial to Likely to be beneficial.

BMJ Clin Evid. 2009 Sep 3;2009:1004.

Cognitive therapy or CBT in adults

Summary

SYMPTOM IMPROVEMENT Cognitive therapy compared with waiting list control: We don't know whether cognitive therapy is more effective in improving symptoms in adults with OCD (very low-quality evidence). CBT compared with waiting list control: CBT may be more effective in improving symptoms (assessed using Yale–Brown Obsessive Compulsive Scale) in adults with OCD (low-quality evidence). Compared with behavioural therapy: We don't know how CBT or cognitive therapy compare with behavioural therapy for improving symptoms in adults with OCD (very low-quality evidence). CBT compared with SRIs: We don't know how CBT compares with sertraline at improving symptoms in adults with OCD (low-quality evidence). QUALITY OF LIFE CBT compared with waiting list control: CBT may be more effective than waiting list control at improving quality of life (as assessed using WHO Quality-Of-Life Assessment Scale) in adults with OCD (low-quality evidence). Compared with SRI: CBT and sertraline seem equally effective at improving quality of life (as assessed using WHO Quality-Of-Life Assessment Scale) in adults with OCD (moderate-quality evidence). NOTE We found no clinically important results from RCTs about SRIs compared with behavioural therapy in adults with OCD. Abrupt withdrawal of SSRIs should be avoided.

Benefits

Cognitive therapy versus waiting list control:

We found one systematic review (search date 2006; 2 RCTs; 50 adults aged 16–65 years with DSM-IV OCD [1 RCT in adults with washing concerns only]) comparing cognitive therapy versus waiting list control. The review found no significant difference between cognitive therapy after 9 to 16 weeks of treatment and waiting list control (8–9 weeks) in symptoms of OCD, assessed using either the Yale–Brown Obsessive Compulsive Scale (YBOCS) or the Maudsley obsessive compulsive inventory (39 adults: SMD –1.21, 95% CI –2.66 to +0.25). The types of cognitive therapy investigated by the identified RCTs were cognitive restructuring and danger ideation reduction therapy (consisting of a combination of different techniques, such as cognitive restructuring, filmed interviews, contamination experiments not involving participants, and strategies of attention focusing).

CBT versus waiting list control:

We found one systematic review (search date 2006; 4 RCTs, 1 quasi-RCT; 149 adults aged 16–65 years with DSM-IV or DSM III-R OCD [1 RCT with few or no overt compulsions; 1 RCT with observable rituals]) comparing CBT versus waiting list control. The review found that CBT significantly improved symptoms of OCD, assessed using YBOCS, after 6 to 20 weeks' treatment compared with waiting list control (4 RCTs, 1 quasi-RCT; 130 adults: WMD –7.73, 95% CI –9.92 to –5.55). The review also found that CBT significantly improved quality of life, assessed using WHO Quality-Of-Life Assessment Scale, compared with waiting list control (1 RCT; 43 adults: WMD –10.50 95% CI –20.74 to –0.26). Two identified RCTs examined group CBT, the rest examined individual CBT.

Cognitive therapy or CBT versus behavioural therapy:

See benefits of behavioural therapy in adults.

Cognitive therapy or CBT versus SRIs:

See benefits of SRIs in adults.

Harms

Cognitive therapy versus waiting list control:

The review gave no information on adverse effects of cognitive therapy. There was no significant difference in the proportion of adults who withdrew from cognitive therapy compared with waiting list control (7/37 [19%] with cognitive therapy v 2/18 [11%] with waiting list control; OR 2.07, 95% CI 0.36 to 11.76).

CBT versus waiting list control:

The review gave no information on specific adverse effects of CBT. However, there was no significant difference in the proportion of adults who withdrew from CBT compared with waiting list control (10/78 [13%] with CBT v 10/71 [14%] with waiting list control; OR 0.88, 95% CI 0.35 to 2.18). One of RCTs identified by the review reported that one person withdrew from the treatment group owing to severe anxiety during response prevention and exposure homework exercises. Another RCT (3-arm study comparing CBT v behavioural therapy plus relaxation v waiting list control) identified by the review found that some people experienced an increase in co-morbid symptoms (panic, depression, or substance misuse) during treatment, and many of these people withdrew (actual numbers and treatment group not reported). One person receiving CBT had a relapse of an alcohol abuse problem, but was able to complete the treatment.

Cognitive therapy or CBT versus behavioural therapy:

See harms of behavioural therapy in adults.

Cognitive therapy or CBT versus SRIs:

See harms of SRIs in adults.

Comment

Clinical guide:

Cognitive and behavioural therapies, and CBT, are effective in OCD. However, some people may find it difficult to engage in or complete these interventions because of excessive anxiety during the exposure. In such people, it may be appropriate to use SSRIs.

Substantive changes

Cognitive therapy or CBT in adults One systematic review added comparing cognitive therapy or CBT versus waiting list control. It found no significant difference between cognitive therapy after 9‒16 weeks' treatment and waiting list control in symptoms of OCD. It found that CBT improved symptoms of OCD after 6‒20 weeks' treatment versus waiting list control. Categorisation changed from Beneficial to Likely to be beneficial.

BMJ Clin Evid. 2009 Sep 3;2009:1004.

SRIs in adults

Summary

SYMPTOM IMPROVEMENT Compared with placebo: SRIs (citalopram, fluoxetine, fluvoxamine, clomipramine, or paroxetine) may be more effective at improving symptoms in adults with OCD. We don't know whether sertraline is more effective at improving symptoms in adults with OCD (very low-quality evidence). Compared with each other: We don't know whether any individual SRI (SSRIs and clomipramine) is more effective than any other at improving symptoms in adults with OCD (low-quality evidence). Compared with venlafaxine: We don't know how SRIs (clomipramine or paroxetine) compare with venlafaxine at improving symptoms in adults with OCD (low-quality evidence). Compared with tricyclic antidepressants (other than clomipramine) and MAOIs: Clomipramine may be more effective than other tricyclic antidepressants and MAOIs (results combined in analysis) at improving symptoms in adults and children. However, we don't know about clomipramine compared with any other individual agent. Fluoxetine may be more effective than phenelzine (MAOI) at improving symptoms over 10 weeks in adults with OCD. Sertraline may be more effective than desipramine at improving symptoms in people with OCD and a major depressive illness (very low-quality evidence). Compared with CBT: We don't know how sertraline compares with CBT at improving symptoms in adults with OCD (low-quality evidence). QUALITY OF LIFE Compared with CBT: Sertraline and CBT seem equally effective at improving quality of life (as assessed using WHO Quality-Of-Life Assessment Scale) in adults with OCD (moderate-quality evidence). NOTE We found no clinically important results about SRIs compared with behavioural therapy in adults with OCD. Abrupt withdrawal of SSRIs should be avoided as it is associated with adverse effects.

Benefits

SRIs (SSRIs and clomipramine) versus placebo:

We found two systematic reviews (search dates 1994 and not reported) and five subsequent RCTs. A number of trials were reported in both reviews; however, they performed different meta-analyses (see table 2 ). Therefore we report results of both here. The two systematic reviews and subsequent RCTs found that the SRIs citalopram, clomipramine, fluoxetine, fluvoxamine, and paroxetine (40–60 mg/day) significantly improved symptoms compared with placebo. One of the subsequent RCTs found no significant difference in symptoms between paroxetine 20 mg daily and placebo. The two reviews found differing results for sertraline compared with placebo. The first review found that sertraline significantly improved symptoms compared with placebo, but the second review found no significant difference in symptoms between sertraline and placebo (see table 2 ). The reviews found heterogeneity in the selection of participants and duration of treatment in the RCTs identified; the first review found that this heterogeneity reached significance in RCTs comparing clomipramine versus placebo. Two RCTs comparing clomipramine versus placebo in the first review included 73 children, but the review did not analyse these RCTs separately. Some RCTs identified by the reviews included people with depression associated with OCD. The first systematic review performed a subgroup analysis in people with OCD without depression and found that, compared with placebo, clomipramine improved symptoms of OCD in people without depression.

Table 2.

SRIs (SSRIs and clomipramine) versus placebo in adults

Intervention and reference Study design Symptom improvement
Citalopram**
  RCT (401 adults aged 18–65 years) AR: 57% with citalopram 20 mg v 52% with citalopram 40 mg v 65% with citalopram 60 mg v 37% with placebo; NNT for citalopram 20 mg v placebo 5, 95% CI 3 to 14
Clomipramine*¶
  SR (9 RCTs; 668 people; 2 RCTs included 73 children and adolescents, 7 RCTs were in adults, no ages reported in review)Subgroup analysis of people with OCD without depression (5 RCTs; 594 people) SMD 1.31, 95% CI 1.15 to 1.47SMD 1.37, 95% CI 1.19 to 1.55
  SR (7 RCTs; 808 people, average ages 35–38 years) SMD –8.19, 95% CI –10.53 to –5.85
Fluoxetine†¶
  SR (1 RCT; 287 adults, ages not reported in review) SMD 0.57, 95% CI 0.33 to 0.81
  SR (3 RCTs; 329 people, average ages 35–38 years) SMD –1.61, 95% CI –2.18 to –1.04
  RCT (355 people aged 15–70 years, mean age 36.9 years) Mean reduction in score: 4.6 with fluoxetine 20 mg, 5.5 with fluoxetine 40 mg, 6.5 with fluoxetine 60 mg v 0.9 with placebo; P < 0.001 for all doses v placebo
Fluvoxamine‡
  SR (3 RCTs; 395 adults ages not reported in review) YBOCS: SMD 0.57, 95% CI 0.37 to 0.77
  SR (4 RCTs; 264 people, average ages 35–38 years) SMD –4.84, 95% CI –7.78 to –1.83 (measured as a change in raw score of Yale–Brown)
  RCT (253 adults aged 18–70 years) Mean reduction in YBOCS score: 8.5 with controlled-release fluvoxamine 100–300 mg v 5.6 with placebo; P = 0.001
Paroxetine¶
  SR (1 RCT; 300 people, average ages 35–38 years) SMD –3.00, 95% CI –4.91 to –1.09
  RCT (348 adults aged 16–78 years, mean age about 40 years) Mean reduction in YBOCS score at 12 weeks: 16% with paroxetine 20 mg/day v 25% with paroxetine 40 mg/day v 29% with paroxetine 60 mg/day v 13% with placebo; significantly greater with paroxetine 40 mg or 60 mg than with placebo, paroxetine 20 mg/day v placebo: NS; P values and CI not reported
  RCT (188 adults aged 16–71 years, mean age about 37 years) Mean difference in YBOCS score between paroxetine (20–50 mg/day) and placebo at 12 weeks: –4.52, 95% CI –6.57 to –22.48; P = 0.00002Proportion of adults "much" or "very much" improved on YBOCS 18-item Likert scale at 12 weeks: 47/94 (50%) with paroxetine v 22/93 (24%) with placebo; P = 0.0003
Sertraline§¶
  SR (3 RCTs; 270 adults ages not reported in review) SMD 0.52, 95% CI 0.27 to 0.77
  SR (4 RCTs; 598 people, average ages 35–38 years) SMD –2.57, 95% CI –6.13 to +1.20; NS

*Total number of different RCTs identified was 11; † total number of different RCTs identified was 5; ‡ total number of different RCTs identified was 6; § total number of different RCTs identified was 4; ¶ symptoms assessed by YBOCS score; **>25% reduction in YBOCS score. NS, not significant; YBOCS, Yale–Brown Obsessive Compulsive Scale.

SRIs (SSRIs and clomipramine) versus each other:

We found two systematic reviews (search date 1994; not reported) and five subsequent RCTs. The systematic reviews and four of the subsequent RCTs all found no significant difference in symptoms between different SRIs (see table 3 ). However, the first subsequent RCT found that sertraline significantly improved symptoms compared with clomipramine (see table 3 ). In this RCT, people taking clomipramine received low doses (median 90 mg/day), which makes the results of the RCT difficult to interpret.

Table 3.

SRIs (SSRIs and clomipramine) versus each other in adults

Study type and reference Population Comparison Results
SR 3 RCTs; 85 adults; ages not reported in review Clomipramine v fluoxetine or fluvoxamine SMD –0.04, 95% CI –0.43 to +0.35
SR Clomipramine v fluvoxamine (4 RCTs; 175 people); clomipramine v fluoxetine (1 RCT; 55 people); clomipramine v paroxetine (1 RCT; 300 people); average ages 35–38 years Clomipramine v fluvoxamine or fluoxetine or paroxetine Clomipramine v fluvoxamine pooled change in YBOCS score: SMD +1.23, 95% CI –1.11 to +3.56; clomipramine v fluoxetine change YBOCS score: SMD +1.40, 95% CI –5.74 to +2.94; clomipramine v paroxetine change in YBOCS score: SMD 0, 95% CI –1.94 to +1.94
RCT 170 adults (aged 18–73 years) Sertraline v clomipramine Mean reduction in YBOCS score: 8%; P = 0.036
RCT 133 adults (aged 17–65 years) Clomipramine v fluvoxamine Change in YBOCS score: 12.6 with clomipramine v 12.3 with fluvoxamine; reported as not significant; no further data reported
RCT 227 adults (aged 18–65 years) Clomipramine (150–300 mg) v fluvoxamine (150–300 mg) Mean reduction in YBOCS score: about 12 in both groups; P value not reported; proportion of adults achieving at least 35% reduction in YBOCS score: 65% with clomipramine v 62% with fluvoxamine; reported as not significant
RCT 150 adults (aged 18–64 years) Sertraline (50–200 mg) v fluoxetine (20–80 mg) Reduction in YBOCS score: 9.6 with sertraline v 9.7 with fluoxetine; CI not reported
RCT 30 adults (mean age about 30 years; age range not reported) Fluvoxamine v paroxetine v citalopram Mean reduction in YBOCS score: 36% with fluvoxamine v 29% with paroxetine v 32% with citalopram; reported as not significant; CI not reported

YBOCS, Yale–Brown Obsessive Compulsive Scale.

SRIs (SSRIs and clomipramine) versus venlafaxine:

We found two RCTs. The first RCT (73 adults aged over 18 years; mean age about 30 years) compared clomipramine (150–225 mg/day, 47 adults) versus venlafaxine (225–350 mg/day, 26 adults). It found no significant difference in response at 12 weeks between clomipramine and venlafaxine (response was defined as 35% or more reduction in the YBOCS score and a Clinical Global Impression Scale score of 2 or more: 9/25 [36%] with venlafaxine v 20/40 [50%] with clomipramine; RR 1.39, 95% CI 0.76 to 2.55, analysis not by intention to treat). The second RCT (150 adults aged 18–65 years; mean age about 35 years) compared paroxetine 60 mg daily versus venlafaxine 300 mg daily for 12 weeks. It found no significant difference between groups in reduction in the YBOCS score or anxiety after 12 weeks (mean reduction in YBOCS score: 7.8 with paroxetine v 7.2 with venlafaxine; P = 0.797; reduction in anxiety, measured using the Hamilton Anxiety Rating Scale: 4.7 with paroxetine v 4.9 with venlafaxine; P = 0.237).

SRIs (SSRIs and clomipramine) versus tricyclic antidepressants (other than clomipramine) and MAOIs:

We found one systematic review and two subsequent RCTs. They found that SRIs significantly improved symptoms compared with tricyclic antidepressants (other than clomipramine) or MAOIs. The systematic review (search date 1994; 7 RCTs; 147 people [ages not reported] with OCD, including 80 adults and 67 children/adolescents) found that, compared with other tricyclic antidepressants (desipramine, imipramine, or nortriptyline) or MAOIs (clorgiline and phenelzine), clomipramine significantly improved symptoms (SMD 0.65, 95% CI 0.36 to 0.92).

The first subsequent RCT (54 adults aged at least 18 years; mean age about 35 years) compared three interventions: fluoxetine, phenelzine (an MAOI), and placebo. It found that fluoxetine significantly improved symptoms over 10 weeks compared with phenelzine (mean reduction in Yale–Brown Obsessive Compulsive Scale (YBOCS) score: 2.8 with fluoxetine v 1.7 with phenelzine; P < 0.05). The second subsequent RCT (164 adults aged at least 18 years; mean age 37.6 years with concurrent OCD and major depressive disorder) found that sertraline significantly increased the proportion of adults who had a clinically important reduction in OCD symptoms compared with desipramine (>40% improvement on YBOCS: 38/79 [48%] with sertraline v 26/85 [31%] with desipramine; P = 0.01) and significantly increased the proportion of adults with remission of depressive symptoms (<7 on Hamilton Depression Rating Scale: 39/79 [49%] with sertraline v 30/85 [35%] with desipramine; P = 0.04).

SRIs (SSRIs and clomipramine) versus behavioural therapy:

We found one systematic review (search date 1997; number of studies and people not reported; included adults and children [age ranges not reported]), which included a meta-analysis. It found no significant difference in symptoms among SRIs, behavioural therapy, and placebo. However, we were unable to draw reliable conclusions as the review made indirect comparisons of effect sizes, and included data from non-randomised studies (see benefits of behavioural or cognitive therapy plus SRIs).

SRIs (SSRIs and clomipramine) versus CBT:

We found one RCT (56 adults aged 18–65 years, mean age 38.5 years) comparing sertraline (100 mg/day) versus cognitive-behavioural group therapy (CBGT) for 12 weeks. The RCT found no significant difference between groups in reduction in YBOCS score from baseline after 12 weeks (YBOCS: change from baseline: 26.1 to 18.8 with sertraline v 25.1 to 14.3 with CBGT; between-group P = 0.083). However, CBGT significantly improved the compulsion-only subscale of the YBOCS compared with sertraline after 12 weeks (YBOCS [compulsions]: change from baseline: 13.5 to 9.4 with sertraline v 12.9 to 6.8 with CBGT; P = 0.030). It found no significant difference between groups in quality of life (assessed using WHO Quality-Of-Life Questionnaire [abbreviated version]) (social component of score: change from baseline: 48.0 to 59.7 with sertraline v 45.7 to 52.3 with CBGT; between-group P = 0.395).

Harms

Harms of SSRIs and clomipramine are well known. See also harms of SSRIs and tricyclic antidepressants in depression in adults: drug and physical treatments and depression in children and adolescents. SSRIs have been linked to suicidal ideation. In clinical trials in children and adolescents with depression, SSRIs have been reported to increased rates of suicide-related events.

SRIs (SSRIs and clomipramine) versus placebo:

The systematic reviews gave no information on adverse effects. The first subsequent RCT found that fluoxetine significantly increased tremor (P < 0.001), dry mouth (P < 0.001), and nausea (P < 0.01) compared with placebo (absolute numbers presented graphically). The second subsequent RCT found that citalopram significantly increased nausea, insomnia, fatigue, sweating, dry mouth, and ejaculatory failure compared with placebo (P < 0.05). The third subsequent RCT found that more people withdrew because of adverse effects with controlled-release fluvoxamine than with placebo (20% with fluvoxamine v 7% with placebo; P value not reported). Compared with placebo, fluvoxamine increased insomnia (35% with fluvoxamine v 20% with placebo), somnolence (27% with fluvoxamine v 11% with placebo), asthenia (25% with fluvoxamine v 8% with placebo), nausea (34% with fluvoxamine v 13% with placebo), diarrhoea (18% with fluvoxamine v 8% with placebo), and anorexia (13% with fluvoxamine v 5% with placebo), and decreased libido (7% with fluvoxamine v 3% with placebo). The fourth subsequent RCT found that the most common adverse effects experienced with paroxetine (60, 40, or 20 mg) compared with placebo at 12 weeks were: abnormal ejaculation (30% with 60 mg v 32% with 40 mg v 19% with 20 mg v 2% with placebo), insomnia (27% with 60 mg v 27% with 40 mg v 15% with 20 mg v 12% with placebo), nausea (18% with 60 mg v 26% with 40 mg v 20% with 20 mg v 8% with placebo), and somnolence (33% with 60 mg v 23% with 40 mg v 25% with 20 mg v 10% with placebo; P values not reported). Headache was less common with paroxetine than with placebo (24% with 60 mg v 28% with 40 mg v 19% with 20 mg v 33% with placebo; P value not reported). The fifth subsequent RCT (191 Japanese people) found that paroxetine significantly increased nausea (28/95 [30%] with paroxetine v 7/94 [7%] with placebo), constipation (13/95 [14%] with paroxetine v 3/94 [3%] with placebo), and insomnia (8/95 [8%] with paroxetine v 0/94 [0%] with placebo), and decreased appetite (10/95 [11%] with paroxetine v 2/94 [2%] with placebo; P < 0.05 for all comparisons) at 12 weeks compared with placebo.

SRIs (SSRIs and clomipramine) versus each other:

The two systematic reviews gave no information on adverse effects. Three subsequent RCTs found that clomipramine increased adverse effects compared with SSRIs, and one subsequent RCT found no significant difference in adverse effects between the SSRIs sertraline and fluoxetine. The first subsequent RCT (170 people) found that significantly more people withdrew because of adverse effects with clomipramine than with sertraline (P < 0.05). Clomipramine was associated with dry mouth, nausea, tremor, anxiety, and constipation, whereas sertraline was associated with nausea and diarrhoea. The second subsequent RCT (133 people) found that clomipramine significantly increased dry mouth (38% with clomipramine v 10% with fluvoxamine) and constipation (26% with clomipramine v 10% with fluvoxamine) compared with fluvoxamine (P < 0.05). The third subsequent RCT comparing clomipramine versus fluvoxamine (227 people) found that more people stopped clomipramine prematurely (withdrawal: 16% with clomipramine v 8% with fluvoxamine; CI not reported), and found that clomipramine significantly increased the proportion of people who had anticholinergic adverse effects (dry mouth: 43% with clomipramine v 10% with fluvoxamine; constipation: 25% with clomipramine v 9% with fluvoxamine; tremor: 22% with clomipramine v 9% with fluvoxamine; and dizziness: 18% with clomipramine v 7% with fluvoxamine; P = 0.05 for frequency of all anticholinergic adverse effects with clomipramine v fluvoxamine). The fourth subsequent RCT found no significant difference in adverse effects between sertraline and fluoxetine. The fifth subsequent RCT gave no information on adverse effects.

One systematic review (search date 1997) of controlled and uncontrolled studies found that the withdrawal rate from adverse effects was 11% with clomipramine, 10% with fluoxetine, 13% with fluvoxamine, 9% with sertraline, and 11% with paroxetine. One non-systematic review of three prospective cohort studies and five surveys found that fluoxetine during pregnancy did not increase the risk of spontaneous abortion or major malformation (numerical values not reported). The review included one prospective cohort study (174 people), and three surveys that found similar outcomes with other SSRIs (sertraline, paroxetine, and fluvoxamine). One prospective cohort study of 55 pre-school children exposed to fluoxetine in utero found no significant difference from unexposed children in global intelligence quotient, language, or behaviour. It included no information on long-term harms for the other SSRIs. The non-systematic review of effects in pregnancy did not describe how articles were selected.Extrapyramidal reactions (including orofacial dystonias) and withdrawal syndrome have been reported more commonly with paroxetine than with other SSRIs. Other alerts and revised prescribing information regarding the use of SSRIs include: the increased risk of persistent pulmonary hypertension in infants born to women who had taken SSRIs during the later half of pregnancy; the increased risk of congenital malformations in infants born to women taking paroxetine during first trimester of pregnancy; and the potential for SSRIs to cause hyponatraemia, particularly in elderly people.

SRIs (SSRIs and clomipramine) versus venlafaxine:

The first RCT found that significantly more people had overall adverse effects with clomipramine than with venlafaxine (43/47 [92%] with clomipramine v 16/26 [62%] with venlafaxine; P = 0.002). It found that, compared with venlafaxine, clomipramine significantly increased the proportion of people who had dry mouth (16/47 [34%] with clomipramine v 3/26 [12%] with venlafaxine; P = 0.036) and constipation (17/47 [36%] with clomipramine v 2/26 [8%] with venlafaxine; P = 0.008). The second RCT found that the most common adverse effects included somnolence (41% with paroxetine v 44% with venlafaxine), sweating (28% with paroxetine v 32% with venlafaxine), constipation (11% with paroxetine v 23% with venlafaxine), insomnia (17% with paroxetine v 39% with venlafaxine), and nausea (27% with paroxetine v 27% with venlafaxine; significance and P values not reported).

SRIs (SSRIs and clomipramine) versus tricyclic antidepressants (other than clomipramine) and MAOIs:

The review gave no information on adverse effects. The second subsequent RCT found that significantly more people discontinued treatment because of adverse effects with desipramine than with sertraline (26% with desipramine v 10% with sertraline; P = 0.009). One systematic review comparing the harms of SSRIs versus tricyclic antidepressants found that SSRIs were associated with fewer anticholinergic adverse effects, but more nausea, diarrhoea, anxiety, agitation, insomnia, and headache.

SRIs (SSRIs and clomipramine) versus behavioural therapy:

The review gave no information on adverse effects.

SRIs (SSRIs and clomipramine) versus CBT:

The RCT did not report on adverse effects of treatments. It found similar withdrawal rates in both groups (3/28 [11%] with sertraline v 3/28 [11%] with CBGT; significance not assessed).

Comment

This section on SRIs includes SSRIs and clomipramine. Clomipramine is also classified as a tricyclic antidepressant.

Factors predicting outcome:

Four RCTs found that people who did not respond to SRIs had a younger age of onset, longer duration of the condition, higher frequency of symptoms, co-existing personality disorders, and a greater likelihood of previous hospital admission. Predictors of good response were older age of onset, history of remissions, no previous drug treatment, more severe OCD, and either high or low score on the Hamilton Depression Rating Scale. Two cohort studies of people with OCD found that poor response to SRIs was predicted by concomitant schizotypal personality disorder, tic disorder, and also severe OCD with cleaning rituals (OR 4.9, 95% CI 1.1 to 21.2).

Clinical guide:

Abrupt withdrawal or marked reduction in the dose of SSRIs should be avoided as it can be associated with adverse effects, such as gastrointestinal disturbances, headache, anxiety, dizziness, paraesthesia, sleep disturbances, fatigue, influenza-like symptoms, and sweating. The dose should be tapered over a few weeks to avoid these effects.

Substantive changes

SRIs in adults One RCT added comparing sertraline versus cognitive-behavioural group therapy found no significant difference between groups in reduction in Yale–Brown Obsessive Compulsive Scale score or quality of life after 12 weeks. Categorisation unchanged (Beneficial).

BMJ Clin Evid. 2009 Sep 3;2009:1004.

Behavioural therapy or cognitive therapy plus SRIs in adults

Summary

SYMPTOM IMPROVEMENT Behavioural or cognitive therapy plus an SRI compared with behavioural or cognitive therapy alone or plus placebo: We don't know whether behavioural or cognitive therapy plus fluvoxamine is more effective at improving symptoms than behavioural or cognitive therapy alone or behavioural therapy plus pill placebo in adults with OCD (very low-quality evidence). Behavioural or cognitive therapy plus an SRI compared with an SRI alone: We don't know whether behavioural or cognitive therapy plus paroxetine or venlafaxine is more effective at improving symptoms than paroxetine or venlafaxine alone in adults with OCD who had previously responded to paroxetine or venlafaxine (very low-quality evidence).

Benefits

We found one systematic review and three subsequent RCTs. The systematic review (search date 1997; 77 studies; number of people not reported; included adults and children [age ranges not reported]; relative number of RCTs or other study types not reported; 70% of treatment comparisons randomised) did not make direct comparisons between treatments. It included all types of study, with the exception of case control studies, and did not describe individual studies included in each analysis, and we were unable to draw reliable conclusions from it (see comment).

Behavioural or cognitive therapy plus SRIs versus behavioural or cognitive therapy alone or plus placebo:

The first subsequent RCT (117 adults aged 18–65 years in an outpatient setting) compared five arms: behavioural therapy, cognitive therapy, behavioural therapy plus fluvoxamine, cognitive therapy plus fluvoxamine, and waiting list control. The comparisons behavioural therapy versus waiting list control and cognitive therapy versus waiting list control are included in a systematic review, which is reported in the sections on behavioural therapy and cognitive therapy. It found no significant difference among interventions in symptoms after 16 weeks of treatment (99 adults: mean reduction in Yale–Brown Obsessive Compulsive Scale [YBOCS] score: 17.1 with behavioural therapy v 13.5 with cognitive therapy v 12.6 with behavioural therapy plus fluvoxamine v 15.6 with cognitive therapy plus fluvoxamine; reported as not significant; no further data reported).

The second subsequent RCT (49 adults [mean age 35.5 years] in a hospital setting) found that behavioural therapy plus fluvoxamine significantly increased the proportion of adults with improved symptoms after 9 weeks of treatment compared with behavioural therapy plus pill placebo (number of adults with >35% reduction in the YBOCS score: 21/24 [88%] with behavioural therapy plus fluvoxamine v 15/25 [60%] with behavioural therapy plus pill placebo; RR 1.46, 95% CI 1.02 to 2.08).

Behavioural or cognitive therapy plus an SRI or venlafaxine versus an SRI or venlafaxine alone:

The third subsequent RCT (96 adults [mean age 36 years] with DSM-IV OCD who had responded to paroxetine or venlafaxine [shown at least a 25% reduction in YBOCS score] in a previous RCT comparing paroxetine versus venlafaxine) compared current drug treatment versus current drug treatment plus behavioural therapy (combination treatment) for a duration of 6 months. Behavioural therapy consisted of exposure and response prevention, and was given as 18 sessions of 45 minutes. The RCT found that combination treatment significantly reduced the YBOCS score compared with current drug treatment alone (mean YBOCS score pre-intervention [0 weeks] to post-intervention [27 weeks]: 14.47 to 10.56 with combination treatment v 14.50 to 18.36 with current drug treatment alone; P < 0.001). However, it found no significant difference between the groups on the Hamilton Anxiety Rating Scale (P = 0.48) or the Hamilton Depression Rating Scale (P = 0.091). These results were based on 80/96 (83%) of people who completed treatment.

Harms

We found no evidence from RCTs or cohort studies of adverse effects from behavioural therapy. Case reports have described unbearable and unacceptable anxiety in some people receiving behavioural therapy.See harms of SRIs in adults and harms of cognitive therapy or CBT in adults.

Behavioural or cognitive therapy plus an SRI versus behavioural or cognitive therapy alone or plus placebo:

The first subsequent RCT reported more somnolence with fluvoxamine (baseline analysis: pre-treatment to 8 weeks: 0% to 17%; P < 0.01; further details, including between-group analysis, not reported) and sweating (baseline analysis: pre-treatment to 16 weeks: 0% to 22%; P = 0.03; further details, including between-group analysis, not reported). The second subsequent RCT gave no information on adverse effects.

Behavioural or cognitive therapy plus an SRI or venlafaxine versus an SRI or venlafaxine alone:

The third subsequent RCT gave no information on adverse effects.

Comment

This section on SRIs includes SSRIs and clomipramine. Clomipramine is also classified as a tricyclic antidepressant. The systematic review found indirect comparisons, similar reductions in symptoms with behavioural therapy plus SRIs (clomipramine, fluoxetine, fluvoxamine, paroxetine, or sertraline) versus placebo. However, we were unable to draw reliable conclusions as the review made indirect comparisons of effect sizes, and included data from non-randomised studies.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Sep 3;2009:1004.

Electroconvulsive therapy in adults

Summary

We found no direct information from RCTs about electroconvulsive therapy in adults with OCD.

Benefits

We found no systematic review or RCTs.

Harms

We found no RCTs.

Comment

People with OCD who also have depression may be treated with electroconvulsive therapy. The evidence for the effects of electroconvulsive therapy in depression is summarised elsewhere in Clinical Evidence (depression in adults: drug and physical treatments).

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Sep 3;2009:1004.

Behavioural therapy in children and adolescents

Summary

We found no direct information from RCTs about behavioural therapy in the treatment of children and adolescents with OCD.

Benefits

We found no systematic review or RCTs.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Behavioural therapy in children and adolescents New option added, for which we found no data satisfying Clinical Evidence inclusion criteria. Categorised as Unknown effectiveness.

BMJ Clin Evid. 2009 Sep 3;2009:1004.

Cognitive therapy or CBT in children and adolescents

Summary

SYMPTOM IMPROVEMENT Compared with waiting list control or placebo: CBT may be more effective at improving symptoms in children and adolescents with OCD (assessed using the children's YBOCS) (very low-quality evidence). Compared with SRIs: We don't know how CBT compares with SRIs at improving symptoms in children and adolescents with OCD (very low-quality evidence). Different types of CBT versus each other: We don't know whether intensive CBT is more effective than once-weekly CBT at improving symptoms in children and adolescents with OCD (low-quality evidence).

Benefits

We found one systematic review (search date 2005; 4 RCTs), evaluating behavioural therapy or CBT in children and adolescents with DSM-IV or DSM III-R OCD.

CBT versus waiting list control or placebo:

The systematic review identified two RCTs comparing CBT and waiting list or placebo control.It found significantly improved OCD symptoms (assessed by the children's version of the Yale–Brown Obsessive Compulsive Scale [children's YBOCS]), with individual or group CBT (after 14 weeks' treatment), compared with waiting list control (4–6 weeks) (1 RCT, 77 children and adolescents [aged 10–13.6 years], WMD [individual CBT v waiting list control]: –15.68, 95% CI –19.02 to –12.34; WMD [group CBT v waiting list control]: –15.76, 95% CI –18.90 to –12.62). The review also found significantly improved OCD symptoms (assessed by children's YBOCS) with individual CBT compared with placebo after 12 weeks (1 RCT, 56 children and adolescents [aged 7–17 years], WMD: –7.50 95% CI –11.55 to –3.45). Individual or group CBT described in both RCTs involved 14 sessions (each duration 1–1.5 hours) and included the following components: psycho education, anxiety management, cognitive therapy, exposure and response prevention, resiliency building, generalisation training, and relapse prevention. The review reported that the description of randomisation in the first RCT suggested quasi-randomisation.

CBT versus SRIs:

The systematic review identified two RCTs (78 children and adolescents aged 7–18 years) comparing CBT and an SRI. It found no significant difference in improvement in OCD symptoms (assessed using children's YBOCS) between CBT and an SRI after 12 weeks' treatment (WMD –3.87, 95% CI –8.15 to +0.41). CBT in one study involved 14 sessions (twice weekly for the first 2 weeks and once weekly thereafter), including: psycho education, anxiety management, cognitive therapy, exposure and response prevention, resiliency building, generalisation training, and relapse prevention. CBT in the other study involved 12 sessions (once weekly) including exposure and response prevention, and cognitive elements for older children. The SRIs used were clomipramine (titrated from 25 mg/day to either 3 mg/kg/day or 200 mg/day over 3–4 weeks) in one RCT and sertraline (titrated from 25 mg/day to 200 mg/day over 6 weeks, followed by adjustment [not defined] for adverse effects) in the other RCT.

We found one subsequent RCT (40 children and adolescents aged 9–17 years with DSM-IV OCD) comparing group CBT versus sertraline (titrated from 25 mg/day [every fourth day] to a max of 200 mg/day or as tolerated [not defined]). It found that both groups had a significant reduction in OCD symptoms (assessed by children's YBOCS) after 12 weeks' treatment, but it did not compare groups (data presented graphically; significance between groups not assessed). Group CBT involved 12 1.5-hour weekly sessions, including psycho education about OCD, cognitive training, exposure and response prevention, and family sessions. The method of randomisation in this RCT was not reported.

Different types of CBT versus each other:

We found one RCT (40 children and adolescents aged 7–17 years with DSM-IV OCD) comparing intensive CBT (one session/weekday) versus once-weekly CBT, for a total of 14 sessions each. It found no significant difference between groups in improvement in OCD symptoms after 14 sessions (children's YBOCS score after 14 sessions: 9.5 with intensive CBT v 12.8 with weekly CBT; P = 0.151). A total of 24/40 (60%) children were also taking medication for their OCD during the study.

Harms

CBT versus waiting list control or placebo:

The review gave no information on adverse effects of CBT, and did not report on the number of withdrawals per study arm of the identified RCTs.

CBT versus SRIs:

The review gave no information on adverse effects of CBT, and did not report on the number of withdrawals per study arm of the identified RCTs. The subsequent RCT found that weight loss was significantly more common with sertraline compared with CBT (absolute numbers not reported; P = 0.020). However, nausea and abdominal pain were significantly more common with CBT compared with sertraline (absolute numbers not reported; nausea: P = 0.043; abdominal pain: P = 0.047). The incidence of all other adverse effects including irritability, headache, dry mouth, tremors, sweating, increase of appetite, and weight gain were reported as similar between groups (absolute numbers and significance not reported). There was one case of acute agitation and insomnia (hypomania) resulting in withdrawal from the study in the sertraline group.

Different types of CBT versus each other:

The RCT gave no information on adverse effects. It found that two children (2/20 [10%]) withdrew from weekly CBT compared with no children (0/20 [0%]) from intensive therapy (significance not assessed).

Comment

None.

Substantive changes

Cognitive therapy or CBT in children and adolescents New option added, for which one systematic review and two RCTs were added. The systematic review found that CBT improved OCD symptoms versus waiting list control or placebo. However, it found no significant difference between CBT and SRIs. One RCT found no significant difference between intensive once a weekday CBT and once-weekly CBT in improvement of OCD symptoms. Categorised as Beneficial.

BMJ Clin Evid. 2009 Sep 3;2009:1004.

SRIs in children and adolescents

Summary

SYMPTOM IMPROVEMENT Compared with placebo: SRIs (SSRIs and clomipramine) may be more effective at improving symptoms in children and adolescents with OCD (very low-quality evidence). Compared with CBT: We don't know how SRIs and CBT compare at improving symptoms in children and adolescents with OCD (very low-quality evidence). NOTE SSRIs have been associated with increased rates of suicide-related events in children and adolescents with depression.

Benefits

SRIs (SSRIs and clomipramine) versus placebo:

We found two systematic reviews (search date not reportedand 2006). A total of four trials in common were reported by both reviews. However, neither review completely superseded the other, and they performed different meta-analyses. Therefore, we report results of both reviews here.

The first review (10 RCTs; 933 children and adolescents aged 6–19 years with OCD) compared the following SRIs: fluoxetine (3 RCTs), paroxetine (2 RCTs), fluvoxamine (1 RCT), sertraline (1 RCT), and clomipramine (3 RCTs) versus placebo. The review found significant improvements in OCD symptoms with each SRI compared with placebo (assessed using either the children’s Yale–Brown Obsessive Compulsive Scale [YBOCS], National Institute of Mental Health [NIMH] Global Obsessive-Compulsive Scale, Clinical Global Impression Scale of severity, or the children's Leyton Obsessional Inventory) (SMD: 6.23 with clomipramine v placebo; P < 0.001; 3.84 with sertraline v placebo; P < 0.001; 3.52 with fluvoxamine v placebo; P < 0.001; 5.56 with fluoxetine v placebo; P < 0.001; 3.95 with paroxetine v placebo; P < 0.001).

The second review (6 RCTs, including 4 RCTs identified by the first review; 718 children and adolescents aged 6–18 years) compared antidepressants (SSRIs, but also venlafaxine, nefazodone, or mirtazapine) versus placebo. It found that antidepressants significantly improved OCD symptoms (assessed using children's YBOCS) compared with placebo (risk difference: 20%, 95% CI 13% to 27%, NNT 6, 95% CI 4 to 8).

SRIs (SSRIs and clomipramine) versus CBT:

See benefits of cognitive therapy or CBT in children and adolescents.

Harms

Harms of SSRIs and clomipramine are well known. See also harms of SSRIs and tricyclic antidepressants in depression in adults: drug and physical treatments and depression in children and adolescents. SSRIs have been linked to suicidal ideation. In clinical trials in children and adolescents with depression, SSRIs have been reported to increase rates of suicide-related events. See harms of SRIs in adults.

SRIs (SSRIs and clomipramine) versus placebo:

The first review gave no information on adverse effects. The second review found no significant difference in suicidal ideation or suicide attempt with antidepressants (SSRIs, venlafaxine, nefazodone, or mirtazapine) versus placebo in children or adolescents with OCD, although rates were higher in children taking antidepressants (ARI +0.5%, 95% CI –1.2% to +2.2%).

SRIs (SSRIs and clomipramine) versus CBT:

See harms of cognitive therapy or CBT in children and adolescents.

Comment

This section on SRIs includes SSRIs and clomipramine. Clomipramine is also classified as a tricyclic antidepressant.

Substantive changes

SRIs in children and adolescents New option added, for which two systematic reviews were added. They found improvements in OCD symptoms with fluoxetine, paroxetine, fluvoxamine, sertraline, and clomipramine versus placebo in children and adolescents. Categorised as Trade-off between benefits and harms.

BMJ Clin Evid. 2009 Sep 3;2009:1004.

Behavioural therapy or cognitive therapy plus SRIs in children and adolescents

Summary

SYMPTOM IMPROVEMENT CBT plus an SRI compared with placebo: CBT plus sertraline may be more effective at improving symptoms in children and adolescents with OCD (low-quality evidence). CBT plus an SRI compared with SRI alone: CBT plus sertraline or fluvoxamine may be more effective at improving symptoms in children and adolescents with OCD (very low-quality evidence). CBT plus an SRI compared with CBT alone: We don't know whether CBT plus sertraline is more effective at improving symptoms in children and adolescents with OCD (low-quality evidence). NOTE SSRIs have been associated with increased rates of suicide-related events in children and adolescents with depression.

Benefits

We found one systematic review (search date 2005; 2 RCTs) evaluating behavioural therapy or CBT combined with medication in children and adolescents with DSM-IV or DSM III-R OCD. CBT in one study involved 14 sessions (twice weekly for the first 2 weeks and once weekly thereafter) including: psycho education, anxiety management, cognitive therapy, exposure and response prevention, resiliency building, generalisation training, and relapse prevention. CBT in the other study involved 20 sessions (once weekly) of exposure and response prevention.

CBT plus SRIs (SSRIs and clomipramine) versus placebo:

The systematic review identified one RCT (56 children and adolescents aged 7–17 years) comparing CBT plus sertraline versus placebo. It found that CBT plus sertraline significantly improved OCD symptoms (assessed using children's Yale–Brown Obsessive Compulsive Scale [YBOCS]) compared with placebo (WMD –10.30, 95% CI –14.06 to –6.54).

CBT plus SRIs (SSRIs and clomipramine) versus SRIs alone:

The systematic review identified two RCTs (76 children and adolescents aged 7–17 years) comparing CBT plus sertraline or fluvoxamine versus an SRI alone. It found that CBT plus an SRI significantly improved OCD symptoms (assessed using children's YBOCS) compared with an SRI alone (WMD –4.55, 95% CI –7.40 to –1.70). The review reported a number of methodological flaws in one identified RCT, including not reporting the method of randomisation or blinding and no statistical between-group comparison reported.

CBT plus SRIs (SSRIs and clomipramine) versus CBT alone:

The systematic review identified one RCT (56 children and adolescents aged 7–17 years) comparing CBT plus sertraline versus CBT alone. It found no significant difference between CBT plus sertraline and CBT alone in improvement of OCD symptoms (assessed using children's YBOCS) (WMD –2.80, 95% CI –7.55 to +1.95).

Harms

CBT plus SRIs versus placebo

:

The review gave no information on adverse effects of CBT, and did not report on the number of withdrawals from each group in the identified RCTs.

CBT plus SRIs versus SRIs alone:

The review gave no information on adverse effects of CBT, and did not report on the number of withdrawals from each group in the identified RCTs.

CBT plus SRIs versus CBT alone:

The review gave no information on adverse effects of CBT, and did not report on the number of withdrawals from each group in the identified RCTs.

Comment

This section on SRIs includes SSRIs and clomipramine. Clomipramine is also classified as a tricyclic antidepressant.

Substantive changes

Behavioural therapy or cognitive therapy plus SRIs in children and adolescents New option added, for which one systematic review was added. It found that CBT plus an SRI improved OCD symptoms versus placebo or an SRI alone, but not versus CBT alone. Categorised as Trade-off between benefits and harms.

BMJ Clin Evid. 2009 Sep 3;2009:1004.

Optimum duration of maintenance treatment with SRIs in adults

Summary

RELAPSE RATES Ongoing SRIs (SSRIs and clomipramine) compared with no ongoing treatment/placebo: We don't know whether ongoing SRIs are more effective than placebo at reducing relapse rates in adults with OCD, who had previously responded to treatment and been on maintenance treatment with SRIs for 20–52 weeks (very low-quality evidence).

Benefits

Ongoing SRIs (SSRIs and clomipramine) versus no ongoing treatment/placebo:

We found three RCTs assessing maintenance of SSRIs in people who had responded to treatment. The first RCT (70 people aged 14–70 years [mean age about 40 years] who had responded to a 20-week course of fluoxetine) found no significant difference between maintenance of fluoxetine and replacement with placebo for 1 year in relapse rate over 1 year (21% with fluoxetine v 32% with placebo; P = 0.137).The second RCT compared sertraline versus placebo in 223 adults (aged >18 years; mean age about 39 years) with OCD, who had all previously responded to 1 years' treatment with sertraline (response defined as at least 25% reduction in Yale–Brown Obsessive Compulsive Scale score from baseline). People continuing on sertraline were prescribed their previous dose (mean 183 mg). The RCT found that, compared with placebo, sertraline significantly reduced the proportion of people who withdrew because of relapse or insufficient clinical response over 24 weeks (9% with sertraline v 24% with placebo; P = 0.006). It found that sertraline also significantly reduced the proportion of people who had worsening of symptoms compared with placebo (12% with sertraline v 35% with placebo; P = 0.001). It found no significant difference in relapse rate over 24 weeks (2.7% with sertraline v 4.4% with placebo; P = 0.34).The third RCT compared continued paroxetine versus placebo in 105 adults (aged 18–75 years) with OCD, who had all previously taken part in an 12-week trial of paroxetine (20, 40, or 60 mg/day) versus placebo, and who had all responded to a further 6 months' treatment with paroxetine (flexible dose starting at 20 mg/day to a maximum of 60 mg/day). People randomised to paroxetine continued on the same dose as that taken during the previous 6 months, and those allocated placebo were switched to it immediately. The RCT found that paroxetine significantly reduced the risk of relapse compared with placebo over 6 months (20/53 [38%] with paroxetine v 30/51 [59%] with placebo; P = 0.033).

Harms

Ongoing SRIs (SSRIs and clomipramine) versus no ongoing treatment/placebo:

The first RCT found no significant difference between fluoxetine and placebo in overall adverse effects (reported as not significant; adverse effects not specified; absolute numbers and CI not reported) or in the proportion of people who withdrew from the trial for any cause over 52 weeks (16/36 [44%] with fluoxetine v 23/35 [66%] with placebo; P = 0.072).The second RCT found that upper respiratory infection, headache, and malaise were reported in 10% or more of people taking sertraline (the RCT did not report rates of these adverse effects with placebo) and that people taking placebo had dizziness and depression (no further data reported). It found that fewer people taking sertraline withdrew because of adverse effects compared with people taking placebo (5/109 [5%] with sertraline v 12/114 [11%] with placebo; P value not reported). The third RCT found that three people (6%) withdrew from paroxetine treatment compared with 20 people (39%) from placebo. The most common adverse effects were dizziness (5/53 [9%] with paroxetine v 18/52 [35%] with placebo), nausea (5/53 [9%] with paroxetine v 14/52 [27%] with placebo), insomnia (4/53 [8%] with paroxetine v 14/52 [27%] with placebo), and an increase in OCD symptoms (neurosis: 7/53 [13%] with paroxetine v 17/52 [33%] with placebo; see comment). Abrupt substitution of paroxetine with placebo may have contributed to adverse effects in the RCT.

Comment

Most RCTs of treatments for OCD are conducted for about 8‒12 weeks. Trials of this length do not provide evidence about the optimum duration of maintenance and preventive treatment for the condition. Longer RCTs with placebo substitution are required to determine this. A few such trials have been conducted recently, the results of which are summarised in the benefits section above. One prospective, 1-year study found further improvement after a 40-week, open-label extension of the study, with continuing adverse effects. One observational study found that 16/18 (89%) people relapsed within 7 weeks of replacing clomipramine with placebo treatment.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Sep 3;2009:1004.

Optimum duration of maintenance treatment with SRIs in children and adolescents

Summary

We found no direct information from RCTs about the optimum duration of maintenance treatment with SRIs in children and adolescents with OCD.

Benefits

We found no systematic reviews or RCTs.

Harms

We found no RCTs

Comment

None.

Substantive changes

Optimum duration of maintenance treatment with SRIs in children and adolescents New option added, for which we found no data satisfying Clinical Evidence inclusion criteria. Categorised as Unknown effectiveness.

BMJ Clin Evid. 2009 Sep 3;2009:1004.

Addition of antipsychotics to SRIs in adults

Summary

SYMPTOM IMPROVEMENT Adding antipsychotics to SRIs (SSRIs and clomipramine) compared with adding placebo to SRIs: Adding antipsychotics to SRIs may be more effective at improving treatment response (assessed by Yale–Brown Obsessive Compulsive Scale) in adults with OCD, who had not responded to SRIs alone (very low-quality evidence). NOTE SRIs and antipsychotics may be associated with adverse effects, including neurological adverse effects (sedation, headache, dizziness, or restlessness), gastrointestinal adverse effects (nausea or increased appetite), and weight gain.

Benefits

Adding antipsychotics to SRIs (SSRIs and clomipramine) versus adding placebo to SRIs:

We found one systematic review (search date 2005) and one additional RCT.

The review (9 RCTs; 278 adults aged >18 years with OCD) compared adding antipsychotics versus adding placebo to SRIs in adults who had not responded to SRIs alone. Response to treatment was defined by a reduction of 35% or more in the Yale–Brown Obsessive Compulsive Scale (YBOCS) score. One RCT identified by the systematic review also included adults who had not responded to venlafaxine or imipramine. All the identified studies in the review were small and the method of randomisation was unclear in all but one RCT. The review found that adding any antipsychotic versus adding placebo to an SRI or venlafaxine or imipramine increased the proportion of responders to treatment after 4‒8 weeks (46/143 [32%] with adding antipsychotic v 15/135 [11%] with adding placebo; ARR 0.22, 95% CI 0.13 to 0.31). The review also stratified the results based on the antipsychotic agent examined. It found that adding haloperidol to fluvoxamine significantly increased the proportion of responders after 4 weeks' treatment compared with adding placebo (1 RCT; 34 adults with OCD who had not responded to 8 weeks of fluvoxamine: 5/17 [29%] with adding haloperidol v 0/17 [0%] with adding placebo; ARR 0.29, 95% CI 0.07 to 0.52). It found that adding risperidone to SRIs significantly increased the proportion of responders after 6‒8 weeks' treatment compared with adding placebo (3 RCTs; 72 adults with OCD who had not responded to 8–12 weeks of an SRI: 15/40 [38%] with adding risperidone v 2/32 [6%] with adding placebo; ARR 0.33, 95% CI 0.14 to 0.51). It found no significant difference in the proportion of responders between adding olanzapine to an SRI after 6 weeks' treatment compared with adding placebo (2 RCTs; 70 adults; 9/35 [26%] with adding olanzapine v 4/35 [11%] with adding placebo, ARR +0.14, 95% CI –0.04 to +0.33); or between adding quetiapine to an SRI compared with adding placebo(or imipramine or venlafaxine) after 6 weeks' treatment (3 RCTs; 102 adults; 17/51 [33%] with adding quetiapine v 9/51 [18%] with adding placebo; ARR 0.16, 95% CI 0 to 0.33).

The additional RCT (27 adults aged 18–49 years who had not responded to 3 months of treatment with fluoxetine, fluvoxamine, or clomipramine in an open-label phase of study) compared adding quetiapine (50–200 mg/day) versus adding placebo to an SRI or clomipramine for 8 weeks. The RCT found that adding quetiapine versus adding placebo to an SRI or clomipramine significantly increased the proportion of adults who responded (response defined as 30% or more reduction in the YBOCS score: 10/14 [71%] with an SRI plus quetiapine v 0/14 [0%] with an SRI plus placebo; P < 0.0001).

Harms

Adding antipsychotics to SRIs (SSRIs and clomipramine) versus adding placebo to SRIs:

The review found no significant difference in the proportion of adults who dropped out, between adding an antipsychotic to an SRI and adding placebo to an SRI (9 RCTs: 14/143 [10%] with antipsychotic plus SRI v 11/135 [8%] with placebo plus SRI; AR difference +0.01, CI –0.06 to +0.08). However, more than half of the adults who dropped out of the placebo plus SRI group were from one RCT. As such, this result should be interpreted with caution. The review reported a significantly higher risk of sedation with an antipsychotic plus an SRI versus placebo plus an SRI in three RCTs (AR difference: risperidone plus SRI v placebo plus SRI: 0.35, 95% CI 0.06 to 0.64; AR difference: quetiapine plus SRI v placebo plus SRI: 0.42, 95% CI 0.14 to 0.69; and AR difference: quetiapine plus SRI v placebo plus SRI: 0.60, 95% CI 0.37 to 0.83). However, one RCT identified by the review reported no significant difference between an antipsychotic plus an SRI and placebo plus an SRI in risk of sedation (AR difference: risperidone plus SRI v placebo plus SRI: +0.30, CI –0.03 to +0.63). The review reported a significantly higher risk of increased appetite with an antipsychotic plus an SRI versus placebo plus SRI in one RCT (AR difference: quetiapine plus SRI v placebo plus SRI: 0.20, 95% CI 0.01 to 0.39). It reported no significant difference between an antipsychotic plus an SRI and placebo plus an SRI in risk of increased appetite from two RCTs (AR difference: risperidone plus SRI v placebo plus SRI: +0.11, CI –0.16 to +0.39; AR difference: quetiapine augmentation plus SRI v placebo plus SRI: –0.05, CI –0.20 to +0.11). The review reported no significant difference in the risk of extrapyramidal adverse effects with SRI plus antipsychotic versus SRI plus placebo from two RCTs (AR difference: risperidone plus SRI v placebo plus SRI: –0.08, CI –0.39 to +0.24; AR difference: risperidone plus SRI v placebo plus SRI: no extrapyramidal symptoms reported in either group; significance not assessed). The systematic review reported no further comparisons of adverse effects from the identified studies.

The following adverse effects were reported in the identified RCTs but not detailed in the review. One RCT found that sedation, restlessness, increased appetite, dry mouth, or tinnitus were experienced by at least 10% of adults taking SRIs plus risperidone, and that blurred vision, excessive perspiration, headache, increased appetite, lightheadedness, restlessness, and sedation were experienced by at least 10% of adults taking SRIs plus placebo. Another RCT found that fluvoxamine plus risperidone was associated with transient sedation in seven adults (7/9 [78%]) and mild appetite increase in three adults (3/9 [33%]). The RCT gave no information on adverse effects with fluvoxamine plus placebo. Another RCT comparing fluoxetine plus olanzapine versus fluoxetine plus placebo found that five adults taking fluoxetine plus olanzapine withdrew from the trial (3 lost to follow-up [reasons not reported]; 1 withdrew because of weight gain; and 1 withdrew because of shaking). Two adults taking fluoxetine plus placebo withdrew (1 because of increased anxiety and 1 because of emotional numbing).

The additional RCT found that adults taking an SRI plus quetiapine had nausea (6/14 [43%]), sedation (3/14 [21%]), and dizziness (1/14 [7%]), and that adults taking an SRI plus placebo had sedation (2/13 [15%]), headache (1/13 [8%]), and nervousness (1/13 [8%]).

Case reports and epidemiological data have suggested increased risk of venous thrombotic events with the use of antipsychotics. Torsades de pointes, QT prolongation, and sudden death have been reported in patients receiving haloperidol particularly those receiving intravenous or higher than recommended doses.

Comment

We found three other systematic review (search dates 2006, 2006, 2005). The review reported in this Clinical Evidence review identified all the studies that were identified by the first and second reviews, and reached the same conclusion. The third review pooled data from studies examining adding drugs from different drug classes, and not just antipsychotic drugs.

Substantive changes

Addition of antipsychotics to SRIs in adults One systematic review added, which identified nine RCTs, four of which were already included in this Clinical Evidence review. It found that adding antipsychotics versus adding placebo to an SRI increased the proportion of treatment responders (adults with a reduction of 35% or more in the Yale–Brown Obsessive Compulsive Scale score). Categorisation unchanged (Likely to be beneficial).


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