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.
| Country | Survey size (adults) | Annual prevalence | Lifetime prevalence |
| Canada | 2200 | 1.4% | 2.3% |
| Puerto Rico | 1200 | 1.8% | 2.5% |
| Germany | 4811 | 1.6% | 2.1% |
| Taiwan | 7400 | 0.4% | 0.7% |
| Korea | 4000 | 1.1% | 1.9% |
| New Zealand | 1200 | 1.1% | 2.2% |
Aetiology/ Risk factors
The cause of OCD is uncertain. In adults: Behavioural, cognitive, genetic, and neurobiological factors have been implicated. Limited evidence from genetic studies in families, and in twins, suggests that genetic factors may be involved, at least in some groups. Risk factors include a family history of OCD, being single (which could be a consequence of the disorder), and belonging to a higher socioeconomic class. The risk of OCD in women is higher than in men in most countries. Other risk factors include cocaine abuse, not being in paid employment, past history of alcohol dependence, affective disorder, and phobic disorder. In children and adolescents: About half of children and adolescents displayed "micro-episodes of OCD" characterised by excessive rigidity and repetitive rituals some years before developing the disorder. Tics in childhood also predicted an increase in OCD symptoms in late adolescence.
Prognosis
In adults: One study (144 people followed for a mean of 47 years) found that an episodic course of OCD was more common during the initial years of the disease (about 1–9 years), but that a chronic course was more common afterwards. Over time, the study found that 39% to 48% of people had symptomatic improvement. A 1-year prospective cohort study found that 46% of people had an episodic course and 54% had a chronic course. 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
| Important outcomes | Symptom improvement, relapse rate, quality of life, adverse effects | ||||||||
| Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of initial treatments for obsessive compulsive disorder in adults? | |||||||||
| 6 (411) | Symptom improvement | Behavioural therapy v waiting list control or placebo treatments (including relaxation) | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and no intention-to-treat analysis |
| 9 (309) | Symptom improvement | Behavioural therapy v cognitive therapy or CBT | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for no intention-to-treat analysis and incomplete reporting of results. Consistency point deducted for different results for different outcomes |
| 2 (39) | Symptom improvement | Cognitive therapy v waiting list control | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for sparse data. Directness points deducted for restricted population in 1 RCT and different time points assessed in intervention and comparison groups |
| 5 (130) | Symptom improvement | CBT v waiting list control | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and quasi-randomisation of 1 RCT |
| 1 (43) | Quality of life | CBT v waiting list control | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| At least 17 (at least 3097 people) | Symptom improvement | SRIs v placebo | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for inclusion of children in 1 systematic review |
| 1 (253) | Quality of life | SRIs v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and no direct statistical assessment reported |
| At least 11 RCTs (at least 1240 people) | Symptom improvement | SRIs v each other | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting. Directness point deducted for low dose of clomipramine used in 1 RCT |
| 1 (56) | Symptom improvement | SRIs v CBT | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for sparse data. Consistency point deducted for different results for different outcomes |
| 1 (56) | Quality of life | SRIs v CBT | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 2 (148) | Symptom improvement | Behavioural therapy (BT) or cognitive therapy (CT) plus SRI v BT/CT alone or plus placebo | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for different results between studies |
| 1 (96) | Symptom improvement | Behavioural or cognitive therapy plus SRI v SRI alone | 4 | –2 | –1 | –1 | 0 | Very low | Quality points deducted for sparse data and no intention-to-treat analysis. Consistency point deducted for different results for different outcomes. Directness point deducted for inclusion of venlafaxine and for population restricted to people who previously responded to drug treatment |
| What are the effects of initial treatments for obsessive compulsive disorder in children and adolescents? | |||||||||
| 1 (20) | Symptom improvement | Behavioural therapy v waiting list control or placebo | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, no blinding, and short follow-up |
| At least 6 (at least 206) | Symptom improvement | CBT v waiting list control or placebo | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for inclusion of unpublished data and quasi-randomisation of 1 RCT. Directness point deducted for inclusion of non-CBT interventions |
| 3 (118) | Symptom improvement | CBT v SRIs | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and methodological weakness in RCTs (not reporting method of randomisation) |
| 12 (at least 933) | Symptom improvement | SRIs v placebo | 4 | –1 | –1 | –1 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for different outcome measures used. Directness point deducted for inclusion of non-SRI antidepressants |
| 1 (29) | Symptom improvement | Different SRIs compared with each other | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and short follow-up. Directness point deducted for no statistical comparison between groups |
| 1 (56) | Symptom improvement | CBT plus SRIs v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 2 (76) | Symptom improvement | CBT plus SRIs v SRIs alone | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, weak methods (not reporting method of randomisation or blinding), and incomplete reporting of results |
| 1 (56) | Symptom improvement | CBT plus SRIs v CBT alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| What are the effects of maintenance treatment for obsessive compulsive disorder in adults? | |||||||||
| 6 (825) | Relapse rates | Ongoing SRIs v no ongoing treatment/placebo | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for methodological weaknesses (small sizes of RCTs and inclusion of unpublished data) and incomplete reporting of results. Directness point deducted for differences in regimens between studies |
| What are the effects of treatments for obsessive compulsive disorder in adults who have not responded to initial treatments? | |||||||||
| 11 (398) | Symptom improvement | Adding antipsychotics to SRIs v adding placebo to SRIs | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for weak methods (unclear method of randomisation in included RCTs). Consistency point deducted for different results for different antipsychotic drugs and between different analyses |
| 3 (79) | Symptom improvement | Transcranial magnetic stimulation (TMS) v sham TMS | 4 | –3 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data, incomplete reporting of results, and short follow-up. Directness point deducted for baseline differences in YBOCS between groups in 1 RCT |
Type of evidence: 4 = RCT.Consistency: similarity of results across studies.Directness: generalisability of population or outcomes. Effect size: based on relative risk or odds ratio.YBOCS, Yale–Brown Obsessive Compulsive Scale.
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.
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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