Clinical Evidence - Obsessive Compulsive Disorder - 2012

Mental health
..................................................
Obsessive compulsive disorder

Search date April 2011
G Mustafa Soomro
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 contin-
uous 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.
QUESTIONS
What are the effects of initial treatments for obsessive compulsive disorder in adults?. . . . . . . . . . . . . . . . . . . . 4
What are the effects of initial treatments for obsessive compulsive disorder in children and adolescents?. . . . 12
What are the effects of maintenance treatment for obsessive compulsive disorder in adults?. . . . . . . . . . . . . 16
What are the effects of maintenance treatment for obsessive compulsive disorder in children and adolescents?. .
1 7
What are the effects of treatments for obsessive compulsive disorder in adults who have not responded to initial
treatments?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
INTERVENTIONS
OCD TREATMENTS IN ADULTS Unknown effectiveness
Beneficial Behavioural therapy in children and adolescents . . 12
SRIs (SSRIs and clomipramine) in adults . . . . . . . . 8
MAINTENANCE FOR OCD IN ADULTS
Likely to be beneficial Unknown effectiveness
Behavioural therapy in adults . . . . . . . . . . . . . . . . . . 4 Ongoing SRIs (SSRIs and clomipramine) versus no on-
CBT in adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 going treatment/placebo in adults . . . . . . . . . . . . . . 16
MAINTENANCE FOR OCD IN CHILDREN

Unknown effectiveness
Behavioural therapy or cognitive therapy plus SRIs Unknown effectiveness
(SSRIs and clomipramine) in adults (unclear if combina- Optimum duration of maintenance treatment with SRIs
tion more effective than behavioural or cognitive therapy in children and adolescents . . . . . . . . . . . . . . . . . . 17
or SRI alone) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Electroconvulsive therapy in adults . . . . . . . . . . . . 12 TREATMENT: NON-RESPONDERS IN ADULTS
Likely to be beneficial
OCD TREATMENTS IN CHILDREN
Addition of antipsychotics to SRIs (SSRIs and
Beneficial clomipramine) in adults . . . . . . . . . . . . . . . . . . . . . . 17
CBT in children and adolescents . . . . . . . . . . . . . . 13
Unknown effectiveness
Trade off between benefits and harms Psychosurgery New . . . . . . . . . . . . . . . . . . . . . . . 19
Behavioural therapy or cognitive therapy plus SRIs Transcranial magnetic stimulation New . . . . . . . . . 19
(SSRIs and clomipramine) in children and adolescents
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 To be covered in future updates
SRIs (SSRIs and clomipramine) in children and adoles- Addition of antipsychotics to SRIs in children and ado-
cents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 lescents
Deep brain stimulation
BMJ Publishing Group Ltd 2012. All rights reserved. .................... 1 .................... Clinical Evidence 2012;01:1004
Mental health
Other adjuvant/augmentation drug treatment Other forms of psychotherapy
Other drug monotherapies
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.
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
[1] [2]
dysfunction. The disorder may have a chronic or an episodic course. Obsessions are recur-
rent 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
[1] [2]
in the criteria for OCD between the DSM-III, DSM-III-R, and DSM-IV and the ICD-10.
INCIDENCE/ In adults: One national, community-based survey of OCD in the UK (1993, 10,000 people) found
[3]
PREVALENCE 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 1674
years) found that 1.1% of those surveyed reported symptoms of OCD during the previous week.
[4]
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
[5]
1.3%, and a lifetime prevalence of 2.3%. Subsequent national surveys used a similar methodol-
ogy 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, p 24 ). 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
[5] [6]
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 In-
stitute of Mental Health (NIMH) Methods for the Epidemiology of Child and Adolescent Mental
Disorders (MECA) Study. The study evaluated a community sample of 1285 carerchild pairs,
where both members of the pair were interviewed using structured interview DISC 2.3 with DSM-
[7]
III-R criteria.
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Mental health
AETIOLOGY/ The cause of OCD is uncertain. In adults: Behavioural, cognitive, genetic, and neurobiological
[8] [9] [10] [11] [12] [13] [14] [15]
RISK FACTORS 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
[10] [16] [17] [18] [19] [20] [21]
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.
[22] [5]
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,
[5]
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
[23]
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 19 years), but that a
[24]
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
[25]
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
[26]
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
[27]
of the disorder, increased OCD duration, and history of inpatient status.
AIMS OF To improve symptoms, and to reduce the impact of illness on social functioning and quality of life,
INTERVENTION with minimal adverse effects of treatment.
OUTCOMES Severity of symptoms; social functioning; and adverse effects of treatment. Commonly used instru-
ments for measuring symptoms include: the YaleBrown Obsessive Compulsive Scale (YBOCS);
the children's version of the YBOCS; the Hamilton Anxiety Rating Scale; and the Hamilton Depres-
sion 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 contrib-
utor 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 ap-
plying the same study design criteria for inclusion as we did for benefits. In addition we use a reg-
ular 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 in-
cluding 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, p 27 ). 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).
BMJ Publishing Group Ltd 2012. All rights reserved. ........................................................... 3

Mental health
QUESTION What are the effects of initial treatments for obsessive compulsive disorder in adults?
OPTION BEHAVIOURAL THERAPY IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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.
For GRADE evaluation of interventions for obsessive compulsive disorder, see table, p 27 .
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
[28] [29] [30]
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 1665 years with DSM-IV or DSM-III-R
[28]
OCD) compared behavioural therapy versus waiting list control. It found that behavioural ther-
apy significantly improved OCD symptoms over 6 to 16 weeks of treatment assessed using the
YaleBrown 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).
[28]
[29] [30]
Two systematic reviews (search dates 1995 and 2007 ) compared behavioural therapy
versus relaxation. The first review (2 RCTs, 121 adults aged 1940 years) found that behavioural
therapy significantly improved symptoms over 4 to 16 weeks of treatment compared with relaxation
[29]
(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.
[30]
The identified RCT (218 people aged 1580 years [mean age 39 years] with DSM-IV OCD,
49% of whom were also taking an SRI) compared three treatments: behavioural therapy guided
[31]
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 be-
havioural 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 im-
provement 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
[31]
therapy; P = 0.001 for relaxation v clinician-guided behavioural therapy; analysis not by ITT).
Behavioural therapy versus cognitive therapy or CBT:

[29] [32] [33] [34] [35] [36]
We found one systematic review and 5 subsequent RCTs.
The systematic review (search date 1995, 4 RCTs, 92 adults aged 1937 years) found no significant
difference in symptoms over 4 to 16 weeks between behavioural therapy and cognitive therapy
[29]
(SMD 0.19; reported as P >0.05; no further data reported).
The first subsequent RCT (76 adults aged 1856 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 be-
havioural 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
[32]
behavioural therapy v 4/31 [13%] with CBT; P = 0.01; analysis not by ITT).
The second subsequent RCT (63 adults aged 1865 years) found no significant difference between
behavioural therapy and cognitive therapy in the proportion of people achieving at least 25% im-
provement in YBOCS score after 16 weeks of treatment (absolute numbers not reported; OR 0.7,
[33]
95% CI 0.2 to 2.0).

Mental health
The third subsequent RCT compared 12 sessions of behavioural therapy versus 12 sessions of
[34]
cognitive therapy. It found that, after treatment, cognitive therapy significantly improved OCD
behaviours (assessed using the Maudsley Obsessional Compulsive Inventory) compared with be-
havioural therapy, but found no significant difference between treatments on the YBOCS score (22
adults aged 1968 years with DSM-III-R diagnosis of OCD; 18 completed treatment; results pre-
sented graphically; P = 0.006 for the Maudsley Inventory; P = 0.022 for YBOCS; not significant
[34]
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
[35]
adults); and ERP (12 adults). The inference-based approach consisted of challenging the pri-
mary 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 infer-
ence, then subsequently challenged the exaggerated appraisals of such inference; and ERP con-
sisted 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
[35]
P = 0.51). The results were based on 44/54 (81%) adults who completed 20 weeks' treatment,
[35]
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
[36]
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
[36]
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
[36]
increased).
Behavioural therapy versus SRIs:

See benefits of SRIs in adults, p 8 .
Harms: Case reports have described unbearable and unacceptable anxiety in some people receiving be-
havioural 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
[28]
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, depres-
sion, 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 be-
[37]
came increasingly suicidal and was removed from the study.
[29] [30] [31]
The reviews and RCT gave no information on adverse effects of behavioural therapy
or relaxation.
Behavioural therapy versus cognitive therapy or CBT:

[29]
The review gave no information on adverse effects of behavioural therapy or CBT. The first,
[32] [33] [35]
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
[34]
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
[36]
not specified).
Behavioural therapy versus SRIs:

See harms of SRIs in adults, p 8 .
Mental health
Comment: We found another systematic review (search date 2006) comparing any psychological treatments
[38]
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 effec-
tive 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
[39] [40]
2.5 months and 32 weeks) and two retrospective cohort studies (total 346 adults [mean
[41] [42]
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
[39] [40] [41]
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
[42]
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
[43]
OCD symptoms at 2 years of follow-up. A prospective non-inception cohort study of behavioural
therapy in 21 adults (aged 1858 years) with OCD (specific diagnostic criteria not reported) found
that, after 2 weeks of treatment, 68% to 79% maintained complete or much improvement in
[44]
symptoms at 3 months of follow-up. In both studies, some people received additional behavioural
therapy during follow-up.
OPTION COGNITIVE THERAPY OR CBT IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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 YaleBrown
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 1665 years with
DSM-IV OCD [1 RCT in adults with washing concerns only]) comparing cognitive therapy versus
[28]
waiting list control. The review found no significant difference between cognitive therapy after
9 to 16 weeks of treatment and waiting list control (89 weeks) in symptoms of OCD, assessed
using either the YaleBrown 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 reduc-
Mental health
tion therapy (consisting of a combination of different techniques, such as cognitive restructuring,
filmed interviews, contamination experiments not involving participants, and strategies of attention
[28]
focusing).
CBT versus waiting list control:

We found one systematic review (search date 2006, 4 RCTs, 1 quasi-RCT, 149 adults aged 1665
years with DSM-IV or DSM-III-R OCD [1 RCT with few or no overt compulsions, 1 RCT with observ-
[28]
able 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.
[28]
Cognitive therapy or CBT versus behavioural therapy:

See benefits of behavioural therapy in adults, p 4 .
Cognitive therapy or CBT versus SRIs:

See benefits of SRIs in adults, p 8 .
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%
[28]
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 signif-
icant difference in the proportion of adults who withdrew from CBT compared with waiting list control
[28]
(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
[45]
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
[37]
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, p 4 .
Cognitive therapy or CBT versus SRIs:

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
[46]
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 psychol-
[47]
ogy and a psychiatrist) versus control (not further defined). It found that religious CBT was
significantly more effective at reducing end of study mean YaleBrown 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.

Mental health
OPTION SRIS IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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 YaleBrown Obsessive Com-
pulsive Scale (YBOCS), in adults with OCD. Clomipramine also seems more effective at improving symptoms, as-
sessed 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:

[48]
We found three systematic reviews (search date 1994, 20 RCTs; search date not reported, 20
[49] [50]
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, p 25 ); however, they reported different meta-analyses and so we report results from all three
here.
All three reviews found that SRIs or SSRIs (analysed together as a group) improved OCD symptoms
[48] [49] [50]
compared with placebo (see table 2, p 25 ). The reviews found that citalopram,
clomipramine, fluoxetine, fluvoxamine, and paroxetine significantly improved symptoms compared
with placebo (see table 2, p 25 ). The reviews found differing results for sertraline compared with
[48] [49] [50]
placebo.
The reviews found heterogeneity in the selection of participants and duration of treatment in the
[48]
RCTs identified; the first review found that this heterogeneity reached significance in RCTs
comparing clomipramine versus placebo. Two RCTs comparing clomipramine versus placebo in
[48]
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
[50]
fluvoxamine versus placebo identified by the third systematic review additionally reported on
[51]
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 im-
provement with fluvoxamine; absolute results for both groups and significance assessment not
reported).
SRIs (SSRIs and clomipramine) versus each other:

[48] [49]
We found two systematic reviews (search dates 1994 and not reported ) and 5 subsequent
[52] [53] [54] [55] [56] [48] [49] [53]
RCTs. The systematic reviews and 4 of the subsequent RCTs
[54] [55] [56]
all found no significant difference in symptoms between different SRIs (see table 3, p
26 ). However, the first subsequent RCT found that sertraline significantly improved symptoms

Mental health
[52]
compared with clomipramine (see table 3, p 26 ). In this RCT, people taking clomipramine re-
ceived low doses (median 90 mg/day), which makes the results of the RCT difficult to interpret.
SRIs (SSRIs and clomipramine) versus behavioural therapy:

We found one systematic review (search date 1997, number of studies and people not reported,
[57]
included adults and children [age ranges not reported]), which included a meta-analysis. It
[57]
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, p 11 ).
SRIs (SSRIs and clomipramine) versus CBT:

We found one RCT (56 adults aged 1865 years, mean age 38.5 years) comparing sertraline
[58]
(100 mg/day) versus cognitive behavioural group therapy (CBGT) for 12 weeks. The RCT found
no significant difference between groups in reduction in YaleBrown 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 im-
proved 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
[58]
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 antide-
pressants 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
[59] [60]
with depression, SSRIs have been reported to increase rates of suicide-related events.
SRIs (SSRIs and clomipramine) versus placebo:

[48] [49]
The first two systematic reviews gave no information on adverse effects.
[50]
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;
[50]
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:
[50]
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
[50]
[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 flu-
[50]
voxamine 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
[50]
v 0/94 [0%] with placebo; RR 6.93, CI 0.36 to 132.39).
Mental health
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,
[50]
95% CI 0.68 to 48.31).
SRIs (SSRIs and clomipramine) versus each other:

[48] [49]
The two systematic reviews gave no information on adverse effects. Three subsequent
[52] [53] [54]
RCTs found that clomipramine increased adverse effects compared with SSRIs, and
[55]
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
[52]
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 fluvox-
amine (dry mouth: 38% with clomipramine v 10% with fluvoxamine; constipation: 26% with
[53]
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 anticholin-
[54]
ergic adverse effects with clomipramine v fluvoxamine). The fourth subsequent RCT found no
[55]
significant difference in adverse effects between sertraline and fluoxetine. The fifth subsequent
[56]
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
[57]
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
[61]
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 unex-
posed 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
[61]
not describe how articles were selected. Extrapyramidal reactions (including orofacial dystonias)
and withdrawal syndrome have been reported more commonly with paroxetine than with other
[62]
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
[63] [64]
to cause hyponatraemia, particularly in older people.
SRIs (SSRIs and clomipramine) versus behavioural therapy:

[57]
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
[58]
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
[65] [66]
weak. One systematic review and meta-analysis found that clomipramine was more effective
than other tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) (results combined
[48]
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
BMJ Publishing Group Ltd 2012. All rights reserved. .......................................................... 10
Mental health
effective than desipramine at improving symptoms in people with OCD and a major depressive ill-
[67] [68]
ness.
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
[69] [70] [71] [72]
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
[73]
disorder, tic disorder, and also severe OCD with cleaning rituals (OR 4.9, 95% CI 1.1 to 21.2).
[74]
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 asso-
ciated with adverse effects, such as gastrointestinal disturbances, headache, anxiety, dizziness,
[62]
paraesthesia, sleep disturbances, fatigue, influenza-like symptoms, and sweating. The dose
should be tapered over a few weeks to avoid these effects.
OPTION BEHAVIOURAL THERAPY OR COGNITIVE THERAPY PLUS SRIS IN ADULTS. . . . . . . . . . . .
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).
[57] [75] [76] [77]
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
[57]
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 1865 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
[28]
control and cognitive therapy versus waiting list control are included in a systematic review,
which is reported in the sections on behavioural therapy, p 4 and cognitive therapy, p 6 . It
found no significant difference among interventions in symptoms after 16 weeks of treatment (99
adults; mean reduction in YaleBrown 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).
[75]
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 flu-
voxamine v 15/25 [60%] with behavioural therapy plus pill placebo; RR 1.46, 95% CI 1.02 to 2.08).
[76]

Mental health
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
[77]
treatment plus behavioural therapy (combination treatment) for a duration of 6 months. Be-
havioural 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
[77]
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 be-
havioural therapy. See harms of SRIs in adults, p 8 and harms of cognitive therapy or CBT in
adults, p 6 .
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
[75]
details, including between-group analysis, not reported). The second subsequent RCT gave
[76]
no information on adverse effects.
Behavioural or cognitive therapy plus an SRI or venlafaxine versus an SRI or venlafaxine

alone:
[77]
The third subsequent RCT gave no information on adverse effects.
antidepressant. The systematic review found indirect comparisons, similar reductions in symptoms
with behavioural therapy plus SRIs (clomipramine, fluoxetine, fluvoxamine, paroxetine, or sertraline)
[57]
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.
OPTION ELECTROCONVULSIVE THERAPY IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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).
QUESTION What are the effects of initial treatments for obsessive compulsive disorder in children and
adolescents?
OPTION BEHAVIOURAL THERAPY IN CHILDREN AND ADOLESCENTS. . . . . . . . . . . . . . . . . . . . . . . .
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.

Mental health
We found one small RCT (20 children and adolescents, aged 817 years; with DSM-IV OCD)
comparing behavioural therapy (up to 10 sessions of exposure and response prevention [ERP]
[78]
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 YaleBrown
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.
[78]
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.
OPTION COGNITIVE THERAPY OR CBT IN CHILDREN AND ADOLESCENTS. . . . . . . . . . . . . . . . . . . .
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 YaleBrown 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
[79]
DSM-IV or DSM-III-R OCD, aged 418 years). The review pooled the results from RCTs eval-
[80]
uating 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-
[79]
based CBT versus family-based relaxation.
It found that individual CBT/BT significantly improved OCD symptoms (assessed using the children's
YaleBrown Obsessive Compulsive Scale [YBOCS]) compared with waiting list control after 4 to
[79]
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 sug-
gested 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).
[79]
The review found no significant difference between family-based CBT versus family-based re-
laxation (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 signifi-
cantly improved OCD symptoms (assessed using children's YBOCS scale) compared with placebo
[79]
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 918 years) compared individ-
ual CBT (10 sessions) versus waiting list control for 12 weeks. It found that CBT significantly im-
proved symptoms compared with waiting list control (mean children's YBOCS score at 12 weeks:
[80]
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 718 years)
[79]
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: psychoedu-
cation, 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 ses-
sions. The SRIs used were clomipramine (titrated from 25 mg/day to either 3 mg/kg/day or
200 mg/day over 34 weeks) in one RCT; sertraline (titrated from 25 mg/day to 200 mg/day over

Mental health
6 weeks, followed by adjustment [not defined] for adverse effects) in the other two RCTs. One of
[79]
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
[79]
withdrawals per study arm of the identified RCTs.
The subsequent RCT reported no adverse effects. One person from each group withdrew before
[80]
the end of the trial, but reasons for these were not reported.
CBT versus SRIs:

[79]
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
[79]
systematic review, separately; see behavioural therapy in children and adolescents, p 12 .
OPTION SRIS IN CHILDREN AND ADOLESCENTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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:

[81] [82]
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 619 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 childrens
YaleBrown 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 ser-
traline v placebo; P <0.001; 3.52 with fluvoxamine v placebo; P <0.001; 5.56 with fluoxetine v
[81]
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 ado-
lescents aged 618 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
[82]
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 718 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
[83]
response; significance assessment for between-group comparisons not reported).
SRIs versus CBT:

See benefits of cognitive therapy or CBT in children and adolescents, p 13 .

Mental health
Harms: Harms of SSRIs and clomipramine are well known. See also harms of SSRIs and tricyclic antide-
pressants 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
[59] [60]
with depression, SSRIs have been reported to increase rates of suicide-related events.
SRIs (SSRIs and clomipramine) versus placebo:

[81]
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, nefa-
zodone, or mirtazapine) versus placebo in children or adolescents with OCD, although rates were
[82]
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 hypo-
manic episode (1 person), and with fluoxetine: headache (1 person), insomnia (1 person), hypo-
[83]
manic episode (1 person), and tremors (2 people).
SRIs versus CBT:

See harms of cognitive therapy or CBT in children and adolescents, p 13 .
antidepressant.
OPTION BEHAVIOURAL THERAPY OR COGNITIVE THERAPY PLUS SRIS IN CHILDREN AND ADO-
LESCENTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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
[79]
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 there-
after) including: psychoeducation, anxiety management, cognitive therapy, exposure and response
prevention, resiliency building, generalisation training, and relapse prevention. CBT in the other
[79]
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 717 years) comparing
CBT plus sertraline versus placebo. It found that CBT plus sertraline significantly improved OCD
symptoms (assessed using children's YaleBrown Obsessive Compulsive Scale [YBOCS]) compared
[79]
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 717 years) com-
paring CBT plus sertraline or fluvoxamine versus an SRI alone. It found that CBT plus an SRI sig-
nificantly 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 sta-
[79]
tistical between-group comparison reported.
CBT plus SRIs (SSRIs and clomipramine) versus CBT alone:

The systematic review identified one RCT (56 children and adolescents aged 717 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
[79]
2.80, 95% CI 7.55 to +1.95).
Mental health
Harms: CBT plus SRIs (SSRIs and clomipramine) versus placebo:
[79]
withdrawals from each group in the identified RCTs.
CBT plus SRIs (SSRIs and clomipramine) versus SRIs alone:

[79]
CBT plus SRIs (SSRIs and clomipramine) versus CBT alone:

[79]
antidepressant.
QUESTION What are the effects of maintenance treatment for obsessive compulsive disorder in adults?
OPTION OPTIMUM DURATION OF MAINTENANCE TREATMENT WITH SRIS IN ADULTS. . . . . . . . . . .
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:

[84] [85]
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], fluox-
etine [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
[84]
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 signifi-
cantly 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.
[85]
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
[84]
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;
[86]
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
[87]
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
[88]
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%]
[88]
with paroxetine v 17/52 [33%] with placebo). Abrupt substitution of paroxetine with placebo
[88]
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
[89]
(7.9% with escitalopram v 8.9% with placebo; significance assessment not reported).

Mental health
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 with-
[85]
drawal 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
[85]
escitalopram v 31.8% with placebo; absolute numbers and P value not reported).
[90]
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
[91]
of the study, with continuing adverse effects. One observational study found that 16/18 (89%)
[92]
people relapsed within 7 weeks of replacing clomipramine with placebo treatment.
QUESTION What are the effects of maintenance treatment for obsessive compulsive disorder in children
and adolescents?
OPTION OPTIMUM DURATION OF MAINTENANCE TREATMENT WITH SRIS IN CHILDREN AND

ADOLESCENTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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.
Comment: None.
QUESTION What are the effects of treatments for obsessive compulsive disorder in adults who have
not responded to initial treatments?
OPTION ADDITION OF ANTIPSYCHOTICS TO SRIS IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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 YaleBrown 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:
[93] [94]
We found two systematic reviews (search dates 2005 and 2010 ) and one additional RCT.
[95]
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 an-
tipsychotics versus adding placebo to SRIs in adults who had not responded to SRIs alone. Re-
sponse to treatment was defined by a reduction of 35% or more in the YaleBrown 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 respon-
ders 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 signif-
Mental health
icantly 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 re-
sponded 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 re-
sponders 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
[93]
[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-
[94]
generation antipsychotic versus SRI plus placebo. The review presented separate analyses
for each antipsychotic drug examined. It found no significant difference between SRI plus olanza-
pine 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 sig-
nificant 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 re-
sponse 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
[94]
+1.55).
The additional RCT (27 adults aged 1849 years who had not responded to 3 months of treatment
with fluoxetine, fluvoxamine, or clomipramine in an open-label phase of study) compared adding
[95]
quetiapine (50200 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).
[95]
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 an-
tipsychotic plus SRI v 11/135 [8%] with placebo plus SRI; AR difference +0.01, CI 0.06 to +0.08).
[93]
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 sig-
nificantly 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
[93]
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:
[93]
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 antipsy-
chotic 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 extrapyra-
[93]
midal 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
Mental health
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
[94]
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%]), se-
dation (3/14 [21%]), and dizziness (1/14 [7%]), and that adults taking an SRI plus placebo had se-
[95]
dation (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
[96]
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
[97]
than recommended doses.
[98] [99] [100]
Comment: We found three other systematic reviews (search dates 2006 and 2005 ). The review
[93]
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
[100]
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 treat-
ment-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 ob-
sessive 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 olanza-
[101]
pine to SRI on YaleBrown Obsessive Compulsive Scale score.
OPTION PSYCHOSURGERY. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . New
We found no direct information from RCTs about psychosurgery in adults with OCD.
[102]
Benefits: We found one systematic review (search date 2002), which found no RCTs (see comment).
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.
[102]
Thus, adequate evidence about effectiveness or otherwise of psychosurgery is not available.
We found no other RCTs or controlled studies.
OPTION TRANSCRANIAL MAGNETIC STIMULATION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . New
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:

[103]
We found one systematic review (search date 2002, 3 RCTs) and three subsequent RCTs.
[104] [105] [106]
The RCTs identified by the review compared repetitive transcranial magnetic stim-
ulation (rTMS) versus either sham rTMS, or application of rTMS to one part of brain versus appli-
cation 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
[103]
RCTs satisfied Clinical Evidence inclusion criteria and so we have not reported these further.

Mental health
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 YaleBrown
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
[104]
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
[104]
caution.
The second subsequent RCT (21 adults with OCD who had not responded to two SRIs and be-
haviour 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
[105]
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 04] = 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;
[105]
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 simul-
[106]
taneously 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
[106]
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:
[103] [104]
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
[105]
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
[106]
sham in terms of adverse effects.
Comment: We found another quasi-randomised controlled trial (alternate allocation) comparing right prefrontal
[107]
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
[107]
of people receiving rTMS.
GLOSSARY
Behavioural therapy Consists of exposure to the anxiety-provoking stimuli, and prevention of ritualistic behaviour
(engaging in compulsions).
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 responsi-
bility) by Socratic questioning, logical reasoning, and hypothesis testing.
Exposure homework Tasks involving contact with anxiety provoking situations to be carried out outside regular
psychotherapy sessions.
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.
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.
Episodic OCD Episodic course with periods of remission since first onset.

Mental health
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 04 or
02 (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 truefalse scale, designed to measure the
total frequency of OCD symptoms. Although the internal consistency, testretest reliability, and validity are satisfac-
tory, 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.
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.
YaleBrown 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 040
(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.
SUBSTANTIVE CHANGES
[102]
Psychosurgery in adults New option added. Categorised as Unknown effectiveness because evidence is of
insufficient quality to judge the effects of psychosurgery in adults.
[103] [104] [105] [106]
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.
[94]
Addition of antipsychotics to SRIs (SSRIs and clomipramine) in adults New evidence added. Categorisation
unchanged (Likely to be beneficial).
[36]
Behavioural therapy in adults New evidence added. Categorisation unchanged (Likely to be beneficial).
[78]
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.
Behavioural therapy or cognitive therapy plus SRIs in children and adolescents Search date updated for already
[79]
included systematic review, but no new evidence found. Categorisation unchanged (Trade-off between benefits
and harms).
[36]
Cognitive therapy or CBT in adults New evidence added. Categorisation unchanged (Likely to be beneficial).
[79] [80]
Cognitive therapy or CBT in children and adolescents New evidence added. Categorisation unchanged
(Beneficial).
[84] [85]
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.
[50] [51]
SRIs (SSRIs and clomipramine) in adults New evidence added. Categorisation unchanged (Beneficial).
SRIs (SSRIs and clomipramine) in children and adolescents Search updated for already included systematic
[79] [83]
review, but no new evidence found. New evidence added. Categorisation unchanged (Trade-off between
benefits and harms).
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89. Fineberg NA, Tonnoir B, Lemming O, et al. Escitalopram prevents relapse of
obsessive-compulsive disorder. Eur Neuropsychopharmacol
2007;17:430439.[PubMed]
G Mustafa Soomro
Consultant Psychiatrist and Tutor
St. James Hospital
Portsmouth
UK
Competing interests: GMS declares no competing interests.
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
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person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, inci-
dental or consequential, resulting from the application of the information in this publication.

Mental health
[5]
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%
BMJ Publishing Group Ltd 2012. All rights reserved. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Mental health
TABLE 2 SRIs (SSRIs and clomipramine) versus placebo in adults (see text, p 8 ).
Intervention and reference Study design Symptom improvement

SRIs or SSRIs (analysed together as a group)
[48]
SSRIs (analysed together as a group) Symptoms assessed by YBOCS score: 8 RCTs, 791 people; SMD 0.47, 95% CI 0.33 to 0.61
[49]
SRIs (analysed together as a group) Symptoms assessed by YBOCS score: 20 RCTs, number of people unclear: SMD 2.57, 95% CI 3.51 to 1.63
SSRIs (analysed together as a group) Symptoms assessed by YBOCS score: 13 RCTs, number of people unclear: SMD 1.85, 95% CI 2.43 to 1.27
[50]
SSRIs (analysed together as a group) Symptoms assessed by YBOCS scale: 17 studies, 3097 people; WMD 3.21, 95% CI 3.84 to 2.57)
Response rate (response defined differently in the original RCTs as improvement in YBOCS or CGI scores): 13 RCTs, proportion
of people who responded: 760/1745 (44%) with SSRIs v 215/952 (23%) with placebo; RR 1.84, 95% CI 1.56 to 2.17
Citalopram
[108] [50]
RCT, identified by review Response (defined as >25% reduction in YBOCS score): 401 adults aged 18 to 65 years: AR: 57% with citalopram 20 mg v 52%
with citalopram 40 mg v 65% with citalopram 60 mg v 37% with placebo; NNT for citalopram 20 mg v placebo: 5, 95% CI 3 to 14
Clomipramine*
[48]
SR Symptoms assessed by YBOCS scale: 9 RCTs, 668 people; 2 RCTs included 73 children and adolescents, 7 RCTs were in
adults, no ages reported in review: SMD 1.31, 95% CI 1.15 to 1.47
Subgroup analysis of people with OCD without depression: 5 RCTs, 594 people; SMD 1.37, 95% CI 1.19 to 1.55
[49]
SR Symptoms assessed by YBOCS scale: 7 RCTs, 808 people, average ages 3538 years: SMD 8.19, 95% CI 10.53 to 5.85
Fluoxetine
[48]
SR Symptoms assessed by YBOCS scale: 1 RCT, 287 adults, ages not reported in review: SMD 0.57, 95% CI 0.33 to 0.81
[49]
SR Symptoms assessed by YBOCS scale: 3 RCTs, 329 people, average ages 35 to 38 years: SMD 1.61, 95% CI 2.18 to 1.04
[50]
SR Symptoms assessed by YBOCS scale: 3 RCTs, 606 people; WMD 3.07, 95% CI 5.32 to 0.82
Response rate: 2 RCTs; 151/426 (35%) with fluoxetine v 22/146 (15%) with placebo; RR 2.41, 95% CI 1.18 to 4.91
Fluvoxamine
[48]
SR Symptoms assessed by YBOCS scale: 3 RCTs, 395 adults ages not reported in review: SMD 0.57, 95% CI 0.37 to 0.77
[49]
SR Symptoms assessed by YBOCS scale: 4 RCTs, 264 people, average ages 35 to 38 years: SMD 4.84, 95% CI 7.78 to 1.83
(measured as a change in raw score of YaleBrown)
[50]
Response rate: 4 RCTs; 117/299 (39%) with fluvoxamine v 41/265 (15%) with placebo; RR 2.68, 95% CI 1.58 to 4.56
Paroxetine
[49]
SR Symptoms assessed by YBOCS scale: 1 RCT, 300 people, average ages 35 to 38 years: SMD 3.00, 95% CI 4.91 to 1.09
[50]
SR Symptoms assessed by YBOCS scale: 3 RCTs, 833 people; WMD 3.36 95% CI 4.55 to 2.17
Response rate: 2 RCTs; 156/298 (52%) with paroxetine v 57/192 (30%) with placebo; RR 1.74, 95% CI 1.28 to 2.36
Sertraline
[48]
SR Symptoms assessed by YBOCS scale: 3 RCTs, 270 adults ages not reported in review: SMD 0.52, 95% CI 0.27 to 0.77
[49]
SR Symptoms assessed by YBOCS scale: 4 RCTs, 598 people, average ages 35 to 38 years: SMD 2.57, 95% CI 6.13 to +1.20;
not significant
[50]
Response rate: 4 RCTs; 162/425 (38%) with sertraline v 58/248 (23%) with placebo; RR 1.54, 95% CI 1.20 to 1.99
BMJ Publishing Group Ltd 2012. All rights reserved. ............................................................................................................ 25

Mental health
Intervention and reference Study design Symptom improvement
*Total number of different RCTs identified was 11. Total number of different RCTs identified was 4. Total number of different RCTs identified was 7. Total number of different RCTs identified was 3. Total
number of different RCTs identified was 5. CGI, Clinical Global Impression; SR, systematic review; YBOCS, YaleBrown Obsessive Compulsive Scale.
TABLE 3 SRIs (SSRIs and clomipramine) versus each other in adults (see text, p 8 ).
Study type and refer-

ence Population Comparison Results
[48]
SR 3 RCTs, 85 adults; ages not reported in review Clomipramine v fluoxetine or fluvoxamine SMD 0.04, 95% CI 0.43 to +0.35
[49]
SR Clomipramine v fluvoxamine (4 RCTs, 175 people); Clomipramine v fluvoxamine or fluoxetine or Clomipramine v fluvoxamine pooled change in YBOCS score: SMD +1.23, 95%
clomipramine v fluoxetine (1 RCT, 55 people); paroxetine CI 1.11 to +3.56; clomipramine v fluoxetine change YBOCS score: SMD +1.40,
clomipramine v paroxetine (1 RCT, 300 people); aver- 95% CI 5.74 to +2.94; clomipramine v paroxetine change in YBOCS score:
age ages 35 to 38 years SMD 0, 95% CI 1.94 to +1.94
[52]
RCT 170 adults (aged 1873 years) Sertraline v clomipramine Mean reduction in YBOCS score: 8%; P = 0.036
[53]
RCT 133 adults (aged 1765 years) Clomipramine v fluvoxamine Change in YBOCS score: 12.6 with clomipramine v 12.3 with fluvoxamine; report-
ed as not significant; no further data reported
[54]
RCT 227 adults (aged 1865 years) Clomipramine (150300 mg) v fluvoxamine Mean reduction in YBOCS score: about 12 in both groups; P value not reported;
(150300 mg) proportion of adults achieving at least 35% reduction in YBOCS score: 65% with
clomipramine v 62% with fluvoxamine; reported as not significant
[55]
RCT 150 adults (aged 1864 years) Sertraline (50200 mg) v fluoxetine Reduction in YBOCS score: 9.6 with sertraline v 9.7 with fluoxetine; CI not report-
(2080 mg) ed
[56]
RCT 30 adults (mean age about 30 years; age range not Fluvoxamine v paroxetine v citalopram Mean reduction in YBOCS score: 36% with fluvoxamine v 29% with paroxetine
reported) v 32% with citalopram; reported as not significant; CI not reported
SR, systematic review; YBOCS, YaleBrown Obsessive Compulsive Scale.

Mental health
TABLE GRADE evaluation of interventions for obsessive compulsive disorder in adults or in children and adolescents
Important outcomes Symptom improvement, relapse rate, quality of life, adverse effects
Type of
Number of studies evi- Consis- Direct- Effect
(participants) Outcome Comparison dence Quality tency ness size GRADE Comment
What are the effects of initial treatments for obsessive compulsive disorder in adults?
[28] [29] [31]
6 (411) Symptom improve- Behavioural therapy v waiting 4 2 0 0 0 Low Quality points deducted for incomplete reporting of re-
ment list control or placebo treat- sults and no intention-to-treat analysis
ments (including relaxation)
[29] [32] [33]
9 (309) Symptom improve- Behavioural therapy v cogni- 4 2 1 0 0 Very low Quality points deducted for no intention-to-treat analysis
[34] [35] [36]
ment tive therapy or CBT and incomplete reporting of results. Consistency point
deducted for different results for different outcomes
[28]
2 (39) Symptom improve- Cognitive therapy v waiting 4 1 0 2 0 Very low Quality point deducted for sparse data. Directness points
ment list control deducted for restricted population in 1 RCT and different
time points assessed in intervention and comparison
groups
[28]
5 (130) Symptom improve- CBT v waiting list control 4 2 0 0 0 Low Quality points deducted for sparse data and quasi-ran-
ment domisation of 1 RCT
[28]
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 Symptom improve- SRIs v placebo 4 0 0 1 0 Moderate Directness point deducted for inclusion of children in 1
[48] [49]
3097 people) ment systematic review
[50]
[51]
1 (253) Quality of life SRIs v placebo 4 2 0 0 0 Low Quality points deducted for incomplete reporting of re-
sults and no direct statistical assessment reported
At least 11 RCTs (at Symptom improve- SRIs v each other 4 1 0 1 0 Low Quality point deducted for incomplete reporting. Direct-
least 1240 peo- ment ness point deducted for low dose of clomipramine used
[48] [49] [52]
ple) in 1 RCT
[53] [54] [55] [56]
[58]
1 (56) Symptom improve- SRIs v CBT 4 1 1 0 0 Low Quality point deducted for sparse data. Consistency point
ment deducted for different results for different outcomes
[58]
1 (56) Quality of life SRIs v CBT 4 1 0 0 0 Moderate Quality point deducted for sparse data
[75] [76]
2 (148) Symptom improve- Behavioural therapy (BT) or 4 2 1 0 0 Very low Quality points deducted for sparse data and incomplete
ment cognitive therapy (CT) plus reporting of results. Consistency point deducted for dif-
SRI v BT/CT alone or plus ferent results between studies
placebo
[77]
1 (96) Symptom improve- Behavioural or cognitive 4 2 1 1 0 Very low Quality points deducted for sparse data and no intention-
ment therapy plus SRI v SRI alone 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?

Mental health
Important outcomes Symptom improvement, relapse rate, quality of life, adverse effects
Type of
Number of studies evi- Consis- Direct- Effect
(participants) Outcome Comparison dence Quality tency ness size GRADE Comment
[78]
1 (20) Symptom improve- Behavioural therapy v waiting 4 3 0 0 0 Very low Quality points deducted for sparse data, no blinding, and
ment list control or placebo short follow-up
At least 6 (at least Symptom improve- CBT v waiting list control or 4 2 0 1 0 Very low Quality points deducted for inclusion of unpublished data
[79] [80]
206) ment placebo and quasi-randomisation of 1 RCT. Directness point
deducted for inclusion of non-CBT interventions
[79]
3 (118) Symptom improve- CBT v SRIs 4 2 0 0 0 Low Quality points deducted for sparse data and methodolog-
ment ical weakness in RCTs (not reporting method of randomi-
sation)
[81]
12 (at least 933) Symptom improve- SRIs v placebo 4 1 1 1 0 Very low Quality point deducted for incomplete reporting of results.
[82]
ment Consistency point deducted for different outcome mea-
sures used. Directness point deducted for inclusion of
non-SRI antidepressants
[83]
1 (29) Symptom improve- Different SRIs compared with 4 2 0 1 0 Very low Quality points deducted for sparse data and short follow-
ment each other up. Directness point deducted for no statistical compari-
son between groups
[79]
1 (56) Symptom improve- CBT plus SRIs v placebo 4 2 0 0 0 Low Quality points deducted for sparse data and incomplete
ment reporting of results
[79]
2 (76) Symptom improve- CBT plus SRIs v SRIs alone 4 3 0 0 0 Very low Quality points deducted for sparse data, weak methods
ment (not reporting method of randomisation or blinding), and
incomplete reporting of results
[79]
1 (56) Symptom improve- CBT plus SRIs v CBT alone 4 2 0 0 0 Low Quality points deducted for sparse data and incomplete
ment reporting of results
What are the effects of maintenance treatment for obsessive compulsive disorder in adults?
[84] [85]
6 (825) Relapse rates Ongoing SRIs v no ongoing 4 2 0 1 0 Very low Quality points deducted for methodological weaknesses
treatment/placebo (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?
[93] [94] [95]
11 (398) Symptom improve- Adding antipsychotics to 4 1 1 0 0 Low Quality point deducted for weak methods (unclear
ment SRIs v adding placebo to method of randomisation in included RCTs). Consistency
SRIs point deducted for different results for different antipsy-
chotic drugs and between different analyses
[104] [105]
3 (79) Symptom improve- Transcranial magnetic stimu- 4 3 0 1 0 Very low Quality points deducted for sparse data, incomplete re-
[106]
ment lation (TMS) v sham TMS porting 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, YaleBrown Obsessive Compulsive Scale.

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Mental health

Obsessive compulsive disorder

MAINTENANCE FOR OCD IN CHILDREN

BMJ Publishing Group Ltd 2012. All rights reserved. ........................................................... 3

OPTION BEHAVIOURAL THERAPY IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Behavioural therapy versus cognitive therapy or CBT:

BMJ Publishing Group Ltd 2012. All rights reserved. ........................................................... 4

Behavioural therapy versus SRIs:

Behavioural therapy versus cognitive therapy or CBT:

Behavioural therapy versus SRIs:

Factors predicting outcome:

OPTION COGNITIVE THERAPY OR CBT IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Benefits: Cognitive therapy versus waiting list control:

CBT versus waiting list control:

Cognitive therapy or CBT versus behavioural therapy:

Cognitive therapy or CBT versus SRIs:

Harms: Cognitive therapy versus waiting list control:

CBT versus waiting list control:

Cognitive therapy or CBT versus behavioural therapy:

Cognitive therapy or CBT versus SRIs:

BMJ Publishing Group Ltd 2012. All rights reserved. ........................................................... 7

Benefits: SRIs (SSRIs and clomipramine) versus placebo:

SRIs (SSRIs and clomipramine) versus each other:

BMJ Publishing Group Ltd 2012. All rights reserved. ........................................................... 8

SRIs (SSRIs and clomipramine) versus behavioural therapy:

SRIs (SSRIs and clomipramine) versus CBT:

SRIs (SSRIs and clomipramine) versus placebo:

SRIs (SSRIs and clomipramine) versus each other:

SRIs (SSRIs and clomipramine) versus behavioural therapy:

SRIs (SSRIs and clomipramine) versus CBT:

SRIs versus other antidepressants:

Factors predicting outcome:

Drug safety alerts:

OPTION BEHAVIOURAL THERAPY OR COGNITIVE THERAPY PLUS SRIS IN ADULTS. . . . . . . . . . . .

BMJ Publishing Group Ltd 2012. All rights reserved. .......................................................... 11

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

OPTION ELECTROCONVULSIVE THERAPY IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Benefits: We found no systematic review or RCTs.

Harms: We found no RCTs.

OPTION BEHAVIOURAL THERAPY IN CHILDREN AND ADOLESCENTS. . . . . . . . . . . . . . . . . . . . . . . .

Benefits: We found no systematic review.

BMJ Publishing Group Ltd 2012. All rights reserved. .......................................................... 12

OPTION COGNITIVE THERAPY OR CBT IN CHILDREN AND ADOLESCENTS. . . . . . . . . . . . . . . . . . . .

CBT versus waiting list control or placebo:

CBT versus SRIs:

BMJ Publishing Group Ltd 2012. All rights reserved. .......................................................... 13

Harms: CBT versus waiting list control or placebo:

CBT versus SRIs:

OPTION SRIS IN CHILDREN AND ADOLESCENTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Benefits: SRIs (SSRIs and clomipramine) versus placebo:

SRIs versus each other:

SRIs versus CBT:

BMJ Publishing Group Ltd 2012. All rights reserved. .......................................................... 14

SRIs (SSRIs and clomipramine) versus placebo:

SRIs versus each other:

SRIs versus CBT:

CBT plus SRIs (SSRIs and clomipramine) versus placebo:

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

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

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

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

OPTION OPTIMUM DURATION OF MAINTENANCE TREATMENT WITH SRIS IN ADULTS. . . . . . . . . . .

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