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BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.
PMCID: PMC3285220

Obsessive compulsive disorder

G Mustafa Soomro, MB BS, MRCPsych, MSc, Consultant Psychiatrist and Tutor

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 April 2011 (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 43 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, optimum duration of maintenance treatment, psychosurgery, serotonin reuptake inhibitors (citalopram, clomipramine, fluoxetine, fluvoxamine, paroxetine, or sertraline), and transcranial magnetic stimulation.

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 or placebo treatments.

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

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

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.

We don't know whether psychosurgery improves OCD because we found no studies of sufficient quality to assess its effectiveness.

Transcranial magnetic stimulation (rTMS) is not likely to improve symptoms of OCD. The quality of evidence is limited with trials being small.

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 US 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 US, 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 ). A subsequent national comorbidity survey replication was carried out between February 2001 to December 2003 in the US (nationally representative sample of 2073 people aged 18 years or older). It found lifetime prevalence of DSM-IV OCD to be 2.3% and 12 months' prevalence to be 1.2%. In children and adolescents: Prevalence in children and adolescents was 2.7% in the US in a community study conducted by the National Institute of Mental Health (NIMH) Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. The study evaluated a community sample of 1285 carer–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 to 64 years.

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. A prospective non-inception cohort study (214 adults with OCD, and follow-up of at least 1 year) found that the probability of full or partial remission after 2 years was 24%; older age of onset, lesser severity of illness, and being female predicted higher probability of full or partial remission. In children and adolescents: One 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 Yale–Brown Obsessive Compulsive Scale (YBOCS); the children's version of the YBOCS; the Hamilton Anxiety Rating Scale; and the Hamilton Depression Rating Scale.

Methods

Clinical Evidence search and appraisal April 2011. The following databases were used to identify studies for this systematic review: Medline 1966 to April 2011, Embase 1980 to April 2011, and The Cochrane Database of Systematic Reviews, March 2011 [online] (1966 to date of issue). When editing this review we used The Cochrane Database of Systematic Reviews 2011, issue 2. An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA) database. 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 contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, at least single blinded, and containing >20 individuals of whom >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 included systematic reviews of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion as we did for benefits. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the 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 ). The categorisation of the quality of the evidence (into high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table 1
GRADE evaluation of interventions for obsessive compulsive disorder in adults or in children and adolescents

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.
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
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
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 4 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
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.
Transcranial magnetic stimulation (TMS)
A non-invasive method that involves using a device that sends magnetic pulses to the brain and in the case of rTMS repetitively. The method has been studied as a therapeutic procedure for OCD. It has also been studied in relation to some neurological and other psychiatric conditions.
Very low-quality evidence
Any estimate of effect is very uncertain.
Yale–Brown Obsessive Compulsive Scale (YBOCS)
A validated, observer-rated scale for measuring symptom scores. It rates the severity of both obsessions and compulsions across 5 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.

Notes

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. 2012; 2012: 1004.
Published online 2012 January 18.

Behavioural therapy in adults

Summary

SYMPTOM IMPROVEMENT Compared with waiting list control or placebo treatments (including relaxation): Behavioural therapy may be more effective than waiting list control or relaxation 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 or placebo treatments (including relaxation):

We found three systematic reviews comparing behavioural therapy versus waiting list control or placebo psychological treatments (including relaxation). The reviews identified different RCTs, and performed different analyses and so we report all three here.

One review (search date 2006, 3 RCTs, 72 adults aged 16–65 years with DSM-IV or DSM-III-R OCD) compared behavioural therapy versus waiting list control. It found that behavioural therapy significantly improved OCD symptoms over 6 to 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 and relapse prevention (ERP) therapy plus relaxation in the third identified study. The analyses in two of the identified RCTs were not by intention to treat (ITT).

Two systematic reviews (search dates 1995 and 2007) compared behavioural therapy versus relaxation. The first review (2 RCTs, 121 adults aged 19–40 years) found that behavioural therapy significantly improved symptoms over 4 to 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 5 subsequent RCTs.

The systematic review (search date 1995, 4 RCTs, 92 adults aged 19–37 years) found no significant difference in symptoms over 4 to 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 (ERP) 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 ERP (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 ERP consisted of standard ERP. 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 ERP 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 ITT.

The fifth subsequent RCT (33 adults [mean age 32 years] with DSM-IV OCD; mean duration of OCD 6 years; mean YBOCS score 25.36) compared behavioural therapy (ERP; given as 20 sessions over 6 months) versus cognitive therapy (given as 18 sessions over 6 months). It found no significant difference between groups in YBOCS score after 6 months of treatment (29 people; 8.31 with ERP v 6.80 with cognitive therapy; P >0.05). It found similar rates of improvement (defined as YBOCS score less-than or equal to 12 plus reduction in YBOCS of at least 6 points) and recovery (defined as YBOCS score less-than or equal to 7 plus reduction in YBOCS of at least 6 points) between groups after 6 months of treatment; however, it did not present a significance assessment of the difference between groups (proportion of people with improvement: 9/13 (69%) with ERP v 13/16 (81%) with cognitive therapy; proportion of people with recovery: 8/13 (62%) with ERP v 11/16 (69%) with cognitive therapy; significance assessment not reported). It found that one person in each group relapsed after 12 months' follow-up (number of people followed-up and whether any additional interventions were provided were unclear). The RCT did not state the method of randomisation used. Some people were on medication during the 3 months before the trial and were allowed to continue with the same medication (but medication could not be changed, or dose increased).

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 or placebo treatments (including relaxation):

The review comparing behavioural therapy versus waiting list control 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 comorbid 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.

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 RCTs 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. The fifth RCT reported that one person each from the behavioural therapy and cognitive therapy groups withdrew from the trial (reasons not specified).

Behavioural therapy versus SRIs:

See harms of SRIs in adults.

Comment

We found another systematic review (search date 2006) comparing any psychological treatments for OCD versus placebo treatments (including relaxation) or waiting list control. The review identified 10 RCTs on exposure and response prevention (ERP) versus placebo treatments or waiting list control, including all the RCTs identified by the first review of behavioural therapy versus waiting list control and two RCTs of behavioural therapy versus relaxation identified by the second and third reviews. The review did not report the total number of people in the analysis, or give details of the significance assessment for this comparison; however, it reported that ERP was highly effective in reducing obsessive compulsive symptoms. A number of the included studies were small, and had methodological weaknesses.

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 New evidence added. Categorisation unchanged (Likely to be beneficial).

BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.

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 at improving symptoms in adults with OCD ( very low-quality evidence ). CBT compared with waiting list control: CBT may be more effective at 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 at improving quality of life (as assessed using WHO Quality-Of-Life Assessment Scale) in adults with OCD (low-quality evidence). CBT compared with SRIs: 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 of 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 comorbid 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

We found one subsequent RCT that compared two interventions: CBT and stress management treatment (SMT) at two different start times: immediate start versus delayed start (after delay of 3 months). The RCT did not present a separate analysis of CBT versus waiting list control. It compared CBT versus SMT; however, it described SMT as an "active and credible treatment" rather than a sham/no active treatment. Therefore, this study did not fulfil Clinical Evidence inclusion criteria for this review. However, we may address the comparison of CBT versus SMT in full in future updates of this review.

We found another subsequent RCT comparing religious CBT (ten 90-minute sessions delivered weekly; supervised by both a clergyman specialised in religious jurisprudence and clinical psychology and a psychiatrist) versus control (not further defined). It found that religious CBT was significantly more effective at reducing end of study mean Yale–Brown Obsessive Compulsive Scale score compared with control. However, it is difficult to interpret the results of this study without the details of the control arm.

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 New evidence added. Categorisation unchanged (Likely to be beneficial).

BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.

SRIs in adults

Summary

SYMPTOM IMPROVEMENT Compared with placebo: SSRIs (citalopram, fluoxetine, fluvoxamine, or paroxetine, analysed together as a group and analysed individually) seem more effective at improving symptoms, assessed by the Yale–Brown Obsessive Compulsive Scale (YBOCS), in adults with OCD. Clomipramine also seems more effective at improving symptoms, assessed by YBOCS, in adults with OCD ( moderate-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 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 placebo: We don't know whether fluvoxamine is more effective at improving quality of life (as assessed using Short Form-36) in adults with OCD (low-quality evidence). 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 three systematic reviews (search date 1994, 20 RCTs; search date not reported, 20 RCTs; and search date 2007, 17 RCTs). The first two reviews examined SRIs (SSRIs or clomipramine) versus placebo in people with OCD, whereas the third review examined only SSRIs versus placebo. The reviews presented pooled analyses of all SRIs or SSRIs (analysed together as a group) versus placebo and additionally presented analyses of each individual SRI versus placebo. A large number of trials were reported in common between all three reviews (see table 2 ); however, they reported different meta-analyses and so we report results from all three here.

Table 1
SRIs (SSRIs and clomipramine) versus placebo in adults (see text).

All three reviews found that SRIs or SSRIs (analysed together as a group) improved OCD symptoms compared with placebo (see table 2 ). The reviews found that citalopram, clomipramine, fluoxetine, fluvoxamine, and paroxetine significantly improved symptoms compared with placebo (see table 2 ). The reviews found differing results for sertraline compared with placebo.

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 third systematic review reported subgroup analyses, based on duration of illness (less-than or equal to 10 years or >10 years), and presence or absence of severe depression. It found that SSRIs (analysed together as a group) were significantly more effective than placebo at improving OCD symptoms, regardless of duration of OCD or presence or absence of severe depression.

A further publication of one RCT (253 adults with DSM-IV OCD, aged 18 years or older) comparing fluvoxamine versus placebo identified by the third systematic review additionally reported on quality-of-life outcomes. It found similar results for difference from baseline in the domains of social functioning, role limitation due to emotional problems, and mental health of the Short Form-36 questionnaire between the two groups after 12 weeks of treatment (reported as no greater improvement with fluvoxamine; absolute results for both groups and significance assessment not reported).

SRIs (SSRIs and clomipramine) versus each other:

We found two systematic reviews (search dates 1994 and not reported) and 5 subsequent RCTs. The systematic reviews and 4 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 1
SRIs (SSRIs and clomipramine) versus each other in adults (see text).

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 Yale–Brown Obsessive Compulsive Scale (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 = 0.03). 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 increase rates of suicide-related events.

SRIs (SSRIs and clomipramine) versus placebo:

The first two systematic reviews gave no information on adverse effects.

The third systematic review reported adverse effects for each SSRI versus placebo separately. It found that nausea, insomnia, and sexual adverse effects were significantly more common with citalopram compared with placebo (1 RCT; nausea: 66/300 [22%] with citalopram v 9/101 [9%] with placebo; RR 2.47, 95% CI 1.28 to 4.77; insomnia: 47/300 [16%] with citalopram v 7/101 [7%] with placebo; RR 2.26, 95% CI 1.06 to 4.84; sexual adverse effects: 27/300 [9%] with citalopram v 0/101 [0%] with placebo; RR 18.64, 95% CI 1.15 to 302.80). It found no significant difference between groups in headache (1 RCT; 50/300 [17%] with citalopram v 16/101 [16%] with placebo; RR 1.05, 95% CI 0.63 to 1.76).

The review found no significant difference between fluoxetine and placebo in the more common adverse effects of nausea, headache, insomnia, and anxiety (2 RCTs; nausea: 92/424 [22%] with fluoxetine v 23/145 [16%] with placebo; RR 1.19, 95% CI 0.44 to 3.25; headache: 105/424 [25%] with fluoxetine v 32/145 [22%] with placebo; RR 1.11, 95% CI 0.79 to 1.58; insomnia: 108/424 [25%] with fluoxetine v 31/145 [21%] with placebo; RR 1.18, 95% CI 0.83 to 1.68; 1 RCT; anxiety: 20/158 [6%] with fluoxetine v 5/56 [9%] with placebo; RR 1.42, 95% CI 0.56 to 3.60).

The review found that insomnia, nausea, somnolence, asthenia, and sexual adverse effects were significantly more common with fluvoxamine compared with placebo (insomnia: 3 RCTs; 76/222 [34%] with fluvoxamine v 41/224 [18%] with placebo; RR 1.81, 95% CI 1.26 to 2.60; nausea: 3 RCTs; 68/222 [31%] with fluvoxamine v 26/224 [12%] with placebo; RR 2.64, 95% CI 1.75 to 3.98; somnolence: 2 RCTs; 59/204 [29%] with fluvoxamine v 24/204 [12%] with placebo; RR 2.46, 95% CI 1.59 to 3.79; asthenia: 2 RCTs; 54/204 [26%] with fluvoxamine v 19/204 [9%] with placebo; RR 2.83, 95% CI 1.74 to 4.60; sexual adverse effects: 3 RCTs; 32/222 [14%] with fluvoxamine v 7/224 [3%] with placebo; RR 4.02, 95% CI 1.85 to 8.73). It found no significant difference between fluvoxamine and placebo in fatigue and headache (fatigue: 1 RCT; 5/18 [28%] with fluvoxamine v 3/20 [15%] with placebo; RR 1.85, 95% CI 0.51 to 6.67; headache: 2 RCTs; 18/98 [18%] with fluvoxamine v 22/100 [22%] with placebo; RR 0.96, 95% CI 0.38 to 2.41).

The review found that insomnia, nausea, somnolence, and constipation were significantly more common with paroxetine compared with placebo (insomnia: 2 RCTs; 108/460 [23%] with paroxetine v 26/188 [14%] with placebo; RR 1.71, 95% CI 1.15 to 2.53; somnolence: 2 RCTs; 92/354 [27%] with paroxetine v 25/183 [14%] with placebo; RR 1.85, 95% CI 1.12 to 3.06; nausea: 1 RCT; 28/94 [29%] with paroxetine v 7/94 [7%] with placebo; RR 3.96, 95% CI 1.82 to 8.61; constipation: 1 RCT; 13/95 [14%] with paroxetine v 3/94 [2%] with placebo; RR 4.29, 95% CI 1.26 to 14.56). It found no significant difference between groups in sexual adverse effects (1 RCT; 3/95 [3%] with paroxetine v 0/94 [0%] with placebo; RR 6.93, CI 0.36 to 132.39).

The review found that insomnia and diarrhoea were significantly more common with sertraline compared with placebo (insomnia: 3 RCTs; 116/370 [31%] with sertraline v 27/209 [13%] with placebo; RR 2.23, 95% CI 1.09 to 4.56; diarrhoea: 92/370 [25%] with sertraline v 20/209 [10%] with placebo; RR 2.16, 95% CI 1.11 to 4.23). It found no significant difference between groups in sexual adverse effects (4 RCTs; 55/380 [14%] with sertraline v 4/218 [2%] with placebo; RR 5.74, 95% CI 0.68 to 48.31).

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 and constipation compared with fluvoxamine (dry mouth: 38% with clomipramine v 10% with fluvoxamine; constipation: 26% with clomipramine v 10% 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; 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 5 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 latter 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 older people.

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.

SRIs versus other antidepressants:

SRIs (SSRIs and clomipramine) are the standard antidepressants used in the treatment of OCD, and other antidepressants are not recommended as they are either unlikely to be effective or of unknown effectiveness. Two RCTs found no significant difference between SRIs (clomipramine or paroxetine) and venlafaxine at improving symptoms in adults with OCD; however, evidence was weak. One systematic review and meta-analysis found that clomipramine was more effective than other tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) (results combined in analysis) at improving symptoms in adults and children. It reported one RCT (37 people) that showed no difference between imipramine and placebo and a second RCT that showed no difference between trazodone and placebo. Two RCTs found that fluoxetine was more effective than phenelzine (MAOI) at improving symptoms over 10 weeks in adults with OCD, and that sertraline was more effective than desipramine at improving symptoms in people with OCD and a major depressive illness.

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).

Drug safety alerts:

A drug safety alert has been issued on the possible small increased risk of congenital cardiac defects associated with fluoxetine in early pregnancy, similar to that seen with paroxetine (http://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON076095).

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 (SSRIs and clomipramine) in adults New evidence added. Categorisation unchanged (Beneficial).

BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.

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 5 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; further data not 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. 2012; 2012: 1004.
Published online 2012 January 18.

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 that is severe and life endangering and not responsive to antidepressants within an acceptable time may be treated with electroconvulsive therapy. In that situation, use of electroconvulsive therapy would be for depression and not for OCD per se. The evidence for the effects of electroconvulsive therapy in depression is summarised elsewhere in Clinical Evidence (see depression in adults: drug and physical treatments).

Substantive changes

No new evidence

BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.

Behavioural therapy in children and adolescents

Summary

Compared with waiting list control: Behavioural therapy may be more effective at improving symptoms in children and adolescents with OCD ( very low-quality evidence ).

Benefits

We found no systematic review.

We found one small RCT (20 children and adolescents, aged 8–17 years; with DSM-IV OCD) comparing behavioural therapy (up to 10 sessions of exposure and response prevention [ERP] over up to 7 weeks) versus waiting list control. It found that behavioural therapy significantly improved symptoms compared with waiting list control after treatment (mean children's Yale–Brown Obsessive Compulsive Scale scores: 13.9 with ERP v 21.1 with waiting list control; mean difference 8.22, 95% CI 0.41 to 16.04; P = 0.04; intention-to-treat analysis). The RCT was open-label, and did not attempt to blind the assessor.

Harms

The RCT did not report any adverse effects. Two people withdrew from the behavioural therapy group and the reason for withdrawal was that they did not want to continue with behaviour therapy.

Comment

None.

Substantive changes

Behavioural therapy in children and adolescents New evidence added. Categorisation unchanged (Unknown effectiveness), because new evidence is insufficient to adequately assess the effects of behavioural therapy in children and adolescents.

BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.

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 Yale–Brown Obsessive Compulsive Scale) ( 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 ( low-quality evidence ).

Benefits

We found one systematic review (search date 2009, 8 RCTs, 343 children and adolescents with DSM-IV or DSM-III-R OCD, aged 4–18 years). The review pooled the results from RCTs evaluating behavioural therapy (BT) or CBT. We found one subsequent RCT.

CBT versus waiting list control or placebo:

The systematic review presented separate analyses for individual-based CBT/BT versus waiting list control, group-based CBT versus waiting list control, individual CBT versus placebo, and family-based CBT versus family-based relaxation.

It found that individual CBT/BT significantly improved OCD symptoms (assessed using the children's Yale–Brown Obsessive Compulsive Scale [YBOCS]) compared with waiting list control after 4 to 14 weeks (3 RCTs, 87 people; WMD –10.71, 95% CI –17.4 to –4.38). The review found that one of the RCTs was unpublished and the description of randomisation in the another RCT suggested quasi-randomisation. Two RCTs included cognitive and behavioural techniques, and one RCT evaluated exposure and response prevention (ERP) only and excluded cognitive techniques. The review found that group CBT significantly improved OCD symptoms (assessed using children's YBOCS) compared with waiting list control after 14 weeks (1 RCT [description of randomisation suggesting quasi-randomisation], 53 people; mean difference –15.76, 95% CI –18.90 to –12.62). The review found no significant difference between family-based CBT versus family-based relaxation (14 weeks) in OCD symptoms using children's YBOCS scale (1 RCT, 42 people; mean difference –2.65, 95% CI –7.41 to +2.11). The systematic review found that individual CBT significantly improved OCD symptoms (assessed using children's YBOCS scale) compared with placebo after 12 weeks (1 RCT, 56 people; mean difference –7.50, 95% CI –11.55 to –3.45).

The subsequent RCT (21 children and adolescents with OCD, aged 9–18 years) compared individual CBT (10 sessions) versus waiting list control for 12 weeks. It found that CBT significantly improved symptoms compared with waiting list control (mean children's YBOCS score at 12 weeks: 12.09 with CBT v 19.06 with waiting list control; P = 0.0161; intention-to-treat analysis).

CBT versus SRIs:

The systematic review identified three RCTs (118 children and adolescents aged 7–18 years) comparing individual or group CBT and an SRI. It found no significant difference in improvement in OCD symptoms (assessed using children's YBOCS) between individual or group CBT and an SRI after 12 weeks of treatment (WMD –3.30, 95% CI –6.62 to +0.01). CBT in one study involved 14 sessions (twice weekly for the first 2 weeks and once weekly thereafter), including: psychoeducation, anxiety management, cognitive therapy, ERP, resiliency building, generalisation training, and relapse prevention. CBT in another study involved 12 sessions (once weekly) including ERP, and cognitive elements for older children. Group CBT in the third study involved 12 (1.5 hour) weekly sessions, including psychoeducation about OCD, cognitive training, ERP, and family sessions. 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; sertraline (titrated from 25 mg/day to 200 mg/day over 6 weeks, followed by adjustment [not defined] for adverse effects) in the other two RCTs. One of the RCTs did not report the method of randomisation, and did not describe loss to follow-up.

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.

The subsequent RCT reported no adverse effects. One person from each group withdrew before the end of the trial, but reasons for these were not reported.

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.

Comment

We have also included the one RCT evaluating ERP versus waiting list control, identified by the systematic review, separately; see behavioural therapy in children and adolescents.

Substantive changes

Cognitive therapy or CBT in children and adolescents New evidence added. Categorisation unchanged (Beneficial).

BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.

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 ( low-quality evidence ). Different SRIs compared with each other: We don't know whether fluoxetine or citalopram is more effective after 6 weeks 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 dates not reported and 2006). A total of 4 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 versus each other:

We found one RCT (29 children and adolescents with DSM-IV OCD, aged 7–18 years) comparing citalopram (20 mg/day) versus fluoxetine (20 mg/day) for 6 weeks. It found similar improvement in OCD symptoms in both groups; however, it did not present a between-group statistical assessment (post-treatment YBOCS mean score: 16.9 with citalopram v 15 with fluoxetine; reported as a similar response; significance assessment for between-group comparisons not reported).

SRIs 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 versus each other:

The RCT reported the following adverse effects with citalopram: headache (1 person) and hypomanic episode (1 person), and with fluoxetine: headache (1 person), insomnia (1 person), hypomanic episode (1 person), and tremors (2 people).

SRIs 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 (SSRIs and clomipramine) in children and adolescents Search updated for already included systematic review, but no new evidence found. New evidence added. Categorisation unchanged (Trade-off between benefits and harms).

BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.

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 2009, 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: psychoeducation, 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 (SSRIs and clomipramine) 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 (SSRIs and clomipramine) 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 (SSRIs and clomipramine) 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 Search date updated for already included systematic review, but no new evidence found. Categorisation unchanged (Trade-off between benefits and harms).

BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.

Optimum duration of maintenance treatment with SRIs in adults

Summary

RELAPSE RATES Ongoing SRIs (SSRIs and clomipramine) compared with no ongoing treatment/placebo: Ongoing SRIs may be more effective than placebo at reducing relapse rates in adults with OCD after 24 to 52 weeks, who had previously responded to treatment ( very low-quality evidence ).

Benefits

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

We found one systematic review (search date 2006, 5 RCTs) and one subsequent RCT assessing maintenance of SSRIs in adults who had responded to treatment.

The systematic review found that SRIs (analysed together as a group; paroxetine [2 RCTs], fluoxetine [1 RCT], sertraline [1 RCT], escitalopram [1 RCT]) significantly reduced relapse compared with placebo during 24 to 52 weeks of follow-up (proportion of relapsers: 68/379 [18%] with SRI v 131/378 [35%] with placebo; RR 0.52, 95% CI 0.41 to 0.66). Most of the included RCTs were small, and one was published in abstract form only. The review did not report the number of people who withdrew from the RCTs, and the RCTs defined response and relapse differently.

The subsequent RCT (68 adults, aged 18 years or older with DSM-IV OCD, who had all responded to open-label treatment with escitalopram for 6 weeks) compared continued escitalopram versus placebo for a further 6 weeks (double-blind discontinuation trial). It found that escitalopram significantly decreased the risk of relapse compared with placebo (proportion of people who relapsed: 24% with escitalopram v 52% with placebo; P = 0.001; absolute numbers not reported). Relapse was defined as increase in Padua total score of 20 to 60 points or as judged by the investigator.

Harms

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

The systematic review did not report on adverse effects, so we have reported adverse effects from the 4 included RCTs that were published in full. One 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). A 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). A 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, nausea, insomnia, and an increase in OCD symptoms (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; increase in OCD symptoms [neurosis]: 7/53 [13%] with paroxetine v 17/52 [33%] with placebo). Abrupt substitution of paroxetine with placebo may have contributed to adverse effects in the RCT. A fourth RCT found that there were no serious adverse effects with escitalopram during the randomised discontinuation phase of the study. It found similar rates of withdrawal (excluding relapses) between escitalopram and placebo (7.9% with escitalopram v 8.9% with placebo; significance assessment not reported).

The subsequent RCT found that two people withdrew from the double-blind discontinuation phase of the study (unclear whether these were from placebo or escitalopram arms and reason for withdrawal not given). The RCT reported that treatment-emergent adverse effects were significantly lower with escitalopram versus placebo in the first 2 weeks after randomisation (proportion of people with treatment-emergent adverse effects: 14.1% with escitalopram v 29.8% with placebo; P <0.001; absolute numbers not reported); however, it reported no significant difference between groups after 2 weeks (proportion of people with treatment-emergent adverse effects: 39.3% with escitalopram v 31.8% with placebo; absolute numbers and P value not reported).

Comment

Most RCTs of treatments for OCD are conducted for about 8 to 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. Several such trials have been conducted, 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

Optimum duration of maintenance treatment with SRIs in adults New evidence added. Categorisation unchanged (Unknown effectiveness) because evidence remains insufficient to adequately assess the effects of this intervention.

BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.

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 review or RCTs.

Harms

We found no RCTs.

Comment

None.

Substantive changes

No new evidence

BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.

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 ( 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 two systematic reviews (search dates 2005 and 2010) and one additional RCT. The two reviews identified 8 RCTs in common; however, they applied different inclusion criteria and performed different analyses and so we have reported both here.

The first systematic 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 increased the proportion of responders to treatment after 4 to 16 weeks (9 RCTs; 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 to 8 weeks of treatment compared with adding placebo (3 RCTs; 72 adults with OCD who had not responded to 8 to 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 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 second systematic review (11 RCTs, 10 RCTs in adults with refractory OCD [refractory to SRI treatment alone], 1 RCT in adults with non-treatment refractory OCD) compared SRI plus second-generation antipsychotic versus SRI plus placebo. The review presented separate analyses for each antipsychotic drug examined. It found no significant difference between SRI plus olanzapine versus SRI plus placebo in OCD symptom scores (2 RCTs, 70 people; YBOCS score at end of study: WMD –2.96, 95% CI –7.14 to +1.22) or in response rate (as defined by the original RCTs, using a predefined reduction in YBOCS) (2 RCTs; 20/35 [57%] with adding olanzapine v 26/35 [74%] with adding placebo; OR 0.28, 95% CI 0.01 to 6.45). It found that adding quetiapine to SRI significantly improved OCD symptom scores compared with adding placebo to SRI (YBOCS score at endpoint: 5 RCTs, 209 people; WMD –2.28, 95% CI –4.05 to –0.52). However, it found no significant difference in response rate (as defined by the original RCTs, using a predefined reduction in YBOCS) (5 RCTs; 64/111 [58%] with adding quetiapine v 77/108 [71%] with adding placebo; OR 0.53, 95% CI 0.27 to 1.05). It found that adding risperidone to SRI significantly improved response rate compared with adding placebo to SRI (3 RCTs; proportion of people with no clinically important response: 32/50 [64%] with adding risperidone v 40/42 [95%] with adding placebo; OR 0.17, 95% CI 0.04 to 0.66). However, it found no significant difference between groups in OCD symptoms score (end of study YBOCS score: 3 RCTs, 91 people; WMD –3.35, 95% CI –8.25 to +1.55).

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. This RCT was excluded by the second review because it was single-blinded. 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 first review found no significant difference in the proportion of adults who withdrew, 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 withdrew from 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 second systematic review found that adding olanzapine to SRI significantly increased weight gain compared with adding placebo to SRI (1 RCT, 44 people; mean difference 2.3 kg, 95% CI 0.80 kg to 3.80 kg). It found that adding quetiapine to SRI significantly increased weight gain and sedation compared with adding placebo to SRI (weight gain: 1 RCT, 76 people; mean difference 3.40 kg, 95% CI 2.15 kg to 4.65 kg; proportion of people with sedation: 4 RCTs; 84/98 [86%] with quetiapine plus SRI v 48/98 [49%] with placebo plus SRI; OR 5.91, 95% CI 2.87 to 12.18). It found no significant difference in tremor between adding quetiapine to SRI and adding placebo to SRI (proportion of people with tremor: 1 RCT; 6/39 [15%] with quetiapine plus SRI v 10/37 [27%] with placebo plus SRI; OR 0.49, 95% CI 0.16 to 1.52). It found that adding risperidone to SRI significantly increased sedation compared with adding placebo to SRI (3 RCTs; 27/50 [54%] with risperidone plus SRI v 8/41 [20%] with placebo plus SRI; OR 7.35, 95% CI 2.07 to 26.11).

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 reviews (search dates 2006 and 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. We found another subsequent RCT examining the effect of adding aripiprazole to usual care of treatment-resistant people with OCD receiving SRIs. This RCT did not fulfil Clinical Evidence inclusion criteria due to poor follow-up. However, we have included a brief comment on it due to the paucity of data on add-on aripiprazole. It found that adding aripiprazole to SRIs significantly improved obsessive compulsive symptoms and was well tolerated.

Adding different antipsychotic drugs versus each other:

We found another RCT that compared adding risperidone to SRI versus adding olanzapine to SRI for 8 weeks. We will address this comparison in full in future updates of this Clinical Evidence review. The RCT found no significant difference between adding risperidone to SRI versus adding olanzapine to SRI on Yale–Brown Obsessive Compulsive Scale score.

Substantive changes

Addition of antipsychotics to SRIs (SSRIs and clomipramine) in adults New evidence added. Categorisation unchanged (Likely to be beneficial).

BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.

Psychosurgery

Summary

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

Benefits

We found one systematic review (search date 2002), which found no RCTs (see comment).

Harms

We found no RCTs.

Comment

One of the inclusion criteria of the review was that the location of the neurosurgical region operated on was validated using magnetic resonance scan or another technique. The review found only one retrospective controlled study and 5 uncontrolled case series on the use of psychosurgery in OCD. Thus, adequate evidence about effectiveness or otherwise of psychosurgery is not available. We found no other RCTs or controlled studies.

Substantive changes

Psychosurgery in adults New option added. Categorised as Unknown effectiveness because evidence is of insufficient quality to judge the effects of psychosurgery in adults.

BMJ Clin Evid. 2012; 2012: 1004.
Published online 2012 January 18.

Transcranial magnetic stimulation

Summary

SYMPTOM IMPROVEMENT Compared with sham treatment: We don't know whether transcranial magnetic stimulation is more effective than sham treatment ( very low-quality evidence ).

Benefits

Transcranial magnetic stimulation (TMS) versus sham TMS:

We found one systematic review (search date 2002, 3 RCTs) and three subsequent RCTs. The RCTs identified by the review compared repetitive transcranial magnetic stimulation (rTMS) versus either sham rTMS, or application of rTMS to one part of brain versus application to a different part of the brain. The review did not pool the data because one RCT did not report pre-crossover data and the remaining two RCTs were clinically heterogeneous. None of the RCTs satisfied Clinical Evidence inclusion criteria and so we have not reported these further.

The first subsequent RCT (37 adults with OCD who had not responded to SSRIs or venlafaxine; 14 in the rTMS group and 5 in the sham group were also taking antipsychotic; all people continued current medication during the trial) compared rTMS (10 sessions, consisting of impulses of 1 Hz with intensity 110% motor threshold given for 30 minutes, i.e., 1800 pulses in 1 session) versus sham procedure over 2 weeks. It found no significant difference between the groups in Yale–Brown Obsessive Compulsive Scale (YBOCS) score after 2 weeks' treatment or after 4 weeks' total follow-up (YBOCS score: after 2 weeks: 22.65 with rTMS v 19.43 with sham; after 4 weeks: 21.16 with rTMS v 16.50 with sham; reported as not significant, P value not reported). However, the RCT found that there was a significant difference between the two groups in baseline YBOCS score (29.00 with rTMS v 24.07 with sham; P <0.0251), and so these results should be interpreted with caution.

The second subsequent RCT (21 adults with OCD who had not responded to two SRIs and behaviour therapy) compared rTMS (intensity 110% of resting motor threshold, 1 Hz, for 10 minutes and 1200 stimuli a day; applied to right prefrontal cortex and supplementary motor area) versus sham treatment over a 2-week period. It found no significant difference in OCD symptoms (assessed by YBOCS) between the groups over 4 weeks of follow-up (mean score at 4 weeks: 23.6 with rTMS v 22.90 with sham; P [for comparison between groups from week 0–4] = 0.92). It found no significant difference between groups in the number of people who responded to treatment (response defined as 25% reduction in YBOCS) (number of responders: 2 with rTMS v 2 with sham; unclear how many people in analysis; P = 1.0).

The third subsequent RCT (21 adults with OCD and residual symptoms despite trial with at least 1 SRI and CBT, 13 people were on SSRIs [not clear whether they continued the medication during the trial] and 5 were on talk therapy during the trial) compared rTMS (intensity 100% of resting motor threshold, 1 Hz, for 20 minutes and thus 1200 stimuli a day; applied to bilaterally and simultaneously to pre-supplementary motor area) versus sham treatment. It found no significant difference in YBOCS score between the groups after 4 weeks (mean YBOCS score: 19.4 with rTMS v 23.5 with sham; reported as not significant, P value not reported).

Harms

Transcranial magnetic stimulation (TMS) versus sham or alternative applications of TMS:

The systematic review and first subsequent RCT did not report on adverse effects.

The second subsequent RCT reported the following adverse effects in the rTMS group; one person had localised scalp pain and two people had transient headache. It gave no information on adverse effects with sham treatment. One person withdrew from rTMS after 5 sessions.

The third subsequent RCT reported that there was no significant difference between rTMS and sham in terms of adverse effects.

Comment

We found another quasi-randomised controlled trial (alternate allocation) comparing right prefrontal high-frequency repetitive rTMS versus sham procedure. This trial did not fulfil Clinical Evidence inclusion criteria; however, we have mentioned a brief comment here, due to the paucity of data on this intervention. The trial found no significant difference between groups in improvement in OCD symptoms over time. It reported that pain during stimulation was the most common complaint of people receiving rTMS.

Substantive changes

Transcranial magnetic stimulation in adults New option added. Categorised as Unknown effectiveness because evidence is of insufficient quality to judge the effects of transcranial magnetic stimulation in adults.


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