Toc TCC
Toc TCC
Toc TCC
S0887-6185(16)30220-1
http://dx.doi.org/doi:10.1016/j.janxdis.2016.08.003
ANXDIS 1869
To appear in:
Received date:
Revised date:
Accepted date:
24-4-2016
12-8-2016
12-8-2016
Lars-Gran sta,b,c, Eili N. Riisec,d, Gro Janne Wergelande, Bjarne Hansenc,d, & Gerd Kvalec,d
Norway
HIGHLIGHTS
CBT yielded very large effect sizes compared to wait list and placebo.
SRIs yielded a moderate effect size compared to placebo.
The addition of SRIs did not potentiate the effect of CBT.
CBT had higher response and remission rate than SRI.
Methodological quality was positively related to the CBT effect size.
Abstract
Obsessive-compulsive disorder (OCD) is ranked by the World Health Organization (WHO)
among the 10 most debilitating disorders. The treatments which have been found effective are
cognitive behavior therapy (CBT) and serotonin reuptake inhibitors (SRI). This meta-analysis
includes all RCTs of CBT (25) and SRI (9) for OCD in youth using the Childrens YaleBrown Obsessive Compulsive Scale (C-YBOCS). CBT yielded significantly lower attrition
(12.7%) than SRI (23.5%) and placebo (24.7%). T h e e f f e c t s i z e s f o r
c o m p ariso n s of
C B T
p lace b o ( 0.9 3 ), an d
w e r e si g n i f ic a nt,
w i th
w a iti n g -list ( 1. 5 3 ),
S R I w i t h
w h ereas
C B T
a n d
C o m b o
n ot.
C o m b o
( C B T + S R I ) vs.
( 6 6 % )
place b o (0.5 1)
vs. S R I ( 0.2 2)
C B T
C B T
S R I ( 4 9 % ), w h i c h
( 2 9 % ) a n d W L C
( 0.1 4 )
w e re
(7 0 % ) a n d
hig h er tha n
w as h i g h er tha n p lace b o
( 1 3 % ) .
A s f o r r e m i s s i o n CBT
(53%) and Combo (49%) were significantly higher than SRI (24%), placebo (15%), and WLC
(10%), which did not differ from each other. Combo was not more effective than CBT alone
irrespective of initial severity of the samples. T h e r a n d o m i z e d
c o ntr olle d trials ( R C T s ) h a ve a n u m b er of
m e t h o d o l o g ical pr o blem s
a n d
w ell as clinical
Keywords: c h i l d r e n , o b s e s s i v e - c o m p u l s i v e
d is or d er, e x p os u re a n d res p o nse prev e nti o n,
c o g n iti ve thera p y,
m e ta -a n a l ysis, s y ste m a ti c
re vie w
1. Introduction
Obsessive-Compulsive disorder (OCD) is a debilitating anxiety disorder characterized
by obsessions and compulsions. Between 1 and 3% of children and adolescents are affected
(Canals, Hernndez-Martnez, Cosi, & Voltas, 2012; Zohar, 1999) and 75% of affected
children and adolescents also have comorbid conditions, with depression, other anxiety
disorders, oppositional defiant disorder, attention-deficit/hyperactivity disorder and Tourettes
disorder being the most common (Geller et al., 2000; Geller et al., 2001a). OCD causes
functional impairment and affects family, social life and academic performance (Piacentini,
Bergman, Keller, & McCracken, 2003). The disorder tends to be chronic with a substantial
proportion of patients still struggling with OCD-symptoms in adulthood (Micali et al., 2010;
Stewart et al., 2004). As many as 30-50% of adults with OCD report symptom onset in
childhood (Rasmussen, 1990).
CBT in the treatment of OCD entails either exposure and response prevention (ERP),
cognitive therapy (CT) or a combination of the two. CBT for pediatric OCD has demonstrated
to be superior to various comparison conditions and active medications in a growing body of
randomized controlled trials (RCTs) over the last fifteen years (McGuire et al., 2015). The
robust findings support CBT as an evidence-based treatment and it is recognized as the
treatment of choice for childhood OCD (AACAP, 2012; NICE, 2005). There is also empirical
support for the use of serotonin reuptake inhibitor (SRI) medication in treating pediatric OCD.
Both tricyclics (clomipramine) (March, Johnston, Jefferson, Kobak, & Greist, 1990; De
Vaugh-Geiss et al., 1992) and selective SRIs such as fluoxetine (e.g. Geller et al. 2004) and
sertraline (March et al., 1998) have been evaluated in several RCTs. Although SRIs have
produced significant symptom reductions relative to placebo, the yield only moderate effect
sizes as compared to large effect sizes for CBT (e.g. McGuire et al., 2015; Ivarsson et al.,
2015). There is also evidence indicating that clinical remission after pharmacological
treatment is not significantly different from placebo (POTS, 2004) and that only 30% of
patients respond to SRIs (Franklin et al., 2011). In line with these findings, the clinical
recommendations are that pharmacological treatment alone (without CBT) should be offered
only if CBT-therapists are unavailable (AACAP, 2012). However, SRI treatment in
combination with CBT is recommended for patients with moderate to severe symptoms or
treatment resistant OCD (AACAP, 2012) suggesting that there is an additional gain in
combining CBT and SRI compared to CBT alone. The empirical support for this
recommendation has been questioned. For instance, Storch et al. (2013) found no significant
difference in treatment effect when comparing CBT+SRI and CBT+Placebo and recent metaanalyses by Snchez-Meca, Rosa-Alczar, Iniesta-Seplveda, and Rosa-Alczar (2014) and
Ivarsson et al. (2015) found that CBT+SRI was not superior to CBT only. The current metaanalysis will include RCTs of CBT or SRI or the combination of the two to evaluate and
compare the efficacy of the different interventions. Hence, the results will contribute to
further illuminate the empirical basis of clinical recommendations in the treatment of OCD.
Previous meta-analyses have also examined treatment for pediatric OCD delivered as
CBT, SRIs or the combination of CBT and SRI. However, many of these have several
limitations. First, the earliest published meta-analyses included both RCTs and non-RCTs
(Abramowitz, Whiteside, & Deacon, 2005; Freeman et al., 2007; O'Kearney, Anstey, & Von
Sanden, 2006). Subsequent meta-analyses have only included RCTs, but Watson and Rees
(2008) only had five CBT-studies, whereas Sanchez-Meca et al. (2014) included 11, McGuire
et al. (2015) had 9, and Skarphedinson et al. (2014) had 13, due to various inclusion criteria
applied. Our meta-analysis included 25 CBT-studies, which means that the overlap with the
most recent meta-analyses varies from 36% to 52%, and it has the most complete coverage of
CBT-studies so far.
1. To evaluate and compare the efficacy of CBT and SRIs in the treatment of pediatric
OCD, both in terms of primary outcome measure and response/remission.
2. To investigate potential moderators of treatment outcome.
3. To evaluate differences in effect due to type of CBT or type of SRIs.
4. To investigate whether there are systematic differences between CBT and SRI trials in
terms of background or treatment data.
5. To provide a thorough evaluation of methodological stringency in CBT and SRI
studies.
6. To provide clinical recommendations as well as recommendations for methodological
improvements in future trials.
2. Method
2.1. Literature search
PsycINFO and PubMed were searched from the start of the data bases to March 1st 2016
with the following search words: Obsessive compulsive disorder OR OCD AND randomized
controlled trial OR RCT OR random* AND youth OR child* OR adolescent OR pediatric.
All abstracts were read and when there was an indication of a group of patients receiving
the particular cognitive-behavioral or drug treatment being compared with another condition
in a RCT the full-text was retrieved. Studies using single case designs were excluded since
there is no consensus yet regarding the calculation of effect sizes for these designs. The
reference lists in the retrieved articles were then checked against the database search and any
other articles that might fulfil the inclusion criteria were retrieved.
2.1.1. Inclusion criteria
In order to be included in the review and meta-analysis a study had to:
Have participants who all were diagnosed with OCD according to DSM or ICD, and
had a maximum age of 18.
Figure 1 shows a flowchart of the inclusion of studies in the present meta-analysis, which was
conducted according to the PRISMA criteria (Liberati et al., 2009).
Patients who fulfilled diagnostic criteria and were offered participation but then
declined and those who accepted participation but did not show up for the first session were
counted as decliners.
2.2.3. Attrition
Patients who participated in at least one session but failed to complete the agreed upon
number of sessions were counted as dropouts. People who completed therapy but did not
show up for the post-treatment assessment were not included in this category.
2.2.4. Type of CBT
Cognitive behavioral treatments were categorized into three subcategories: ERP with
no cognitive therapy, CT with no ERP (but with behavioral experiments), or the combination
(ERP+CT).
2.2.5. Format and parental involvement
Format of therapy was classified as individual, group, or family treatment. Degree of
parental involvement was classified as low if parents are not present during sessions but
informed about progress of therapy, moderate if parents are present during some therapy
sessions full-time or only part-time of all sessions and high if parents are present full-time
during all therapy sessions.
2.2.6. Statistical analysis
Statistical analysis was categorized as intent-to-treat (ITT) if all randomized
participants are included in the statistical analysis and completers if dropouts were deleted.
2.2.7. Reliability of categorizations
The categorizations were done independently by the first and the second author
yielding a mean agreement of 90%. Disagreements were solved after consensus discussions.
10
2.5. Meta-analysis
In the current meta-analysis the clinician-administered C-YBOCS (or Y-BOCS) was
used to calculate effect size for each study. This was the primary outcome measure in the
included studies. When a study presented intent-to-treat (ITT) data these were used, if not
11
completer data were used. The effect size (ES) was calculated as: (Mactive treatment
Mcomparison)/SDpooled, separately for post- and follow-up assessment. Within-group ES was
calculated as (Mpre Mpost)/SDpre according to recommendations by Morris and DeShon
(2002). The mean ES was computed by weighting each ES by the inverse of its variance.
Before pooling the effect sizes we screened for statistical outliers, defined as being
outside M 2SD. Two (3.9%) of the ESs were outliers, and winsorising (Lipsey & Wilson,
2001) was used by reducing outliers to the exact value of M+2SD. The software
Comprehensive Meta-Analysis, version 2.2.057 (CMA; Biostat Inc., 2006) was used for all
analyses and to correct for small sample sizes Hedgess g was calculated. A random effects
model was used since it cannot be assumed that the ESs come from the same population as
studies comparing CBT conditions with waitlist, placebo, medication and other forms of CBT,
and SRI with placebo are included in the meta-analysis.
Heterogeneity among ESs was assessed with the Q- and the I-square statistic. The
possibility of publication bias was analyzed with the trim-and-fill method of Duval and
Tweedie (2000) as well as Eggers regression intercept (Egger, Davey Smith, Schneider, &
Minder, 1997). Moderator analyses of continuous variables were carried out with metaregression and for categorical variables with sub-group analysis using the mixed effect model.
3. Results
3.1. Description of the studies
3.1.1. Background data
Background data for the 34 included studies (25 CBT, 9 SRI) are displayed in
Appendix Table A.1. The most common country of origin was USA (21), followed by Great
Britain (6), Australia (2), Brazil (2), and Germany, Holland, and Norway (1 each). The
diagnostic systems used were DSM-IV (28), DSM-III-R (4), and DSM-III (2). In total 1990
12
patients participated in the 34 studies. Proportions of patients who fulfilled inclusion criteria
but declined participation for various reasons were provided by 22 studies (65%). A
significantly higher proportion of CBT- (76%) than SRI-studies (33%) provided this
information (Fishers exact probability test, p = 0.040, two-tailed). The declining proportion
varied from 0% to 53.3%, with a mean of 7.4% (SD 9.7) and Mdn of 4.3%. There was no
significant difference between CBT- and SRI-studies in this respect.
Proportion of females was given by 33 studies and the mean was 45.9% (SD 9.3;
CBT- 48.8%, SRI-studies 43.9%. The mean age of the samples varied from 5.8 to 15.0 with a
mean of 12.5 (SD 2.1; CBT- 12.4, SRI-studies M 13.0). Only 14 studies (42%) reported age
of onset in their samples and this varied from 5.1 to 13.3 with a mean of 8.5 (SD 2.1). Percent
comorbidity was described by 28 studies (82%) and it ranged from 11% to 97% with a mean
of 54.3 (SD 2.3). There was a significantly higher (Qbetween (df 1) = 34.34, p = 0.0001)
proportion of patients with comorbidity in CBT- (68.9%) than in SRI-studies (31.3%).
Finally, the mean pre-treatment severity of OCD (on CY-BOCS) was 24.6 (CBT 24.6, SRI
24.5, Combo 25.6, and placebo 24.9).
3.1.2. Treatment data
Treatment data for the included studies are presented in Appendix Table A.2,
separately for CBT- and SRI-studies. Format was individual treatment in 14 studies, family
treatment in 9, and group treatment in two studies. The treatment period varied from 3 to 20
weeks with a mean of 12.7 (SD 3.8). Number of sessions varied from 9 to 14 with a mean of
12.5 (SD 1.6), and the total hours of therapy ranged from 10 to 22.5, with a mean of 15.4 (SD
4.2). Follow-up assessment was reported for 15 (60%) of the CBT-studies with a mean
follow-up period of 5.5 (SD 8.0) months. However, for those studies reporting follow-up
assessment the mean was 9.2 months.
13
In the 9 pharmacological treatment studies comparing active drug with placebo the
following drugs were used: clomipramine (2), fluoxetine (3), fluvoxamine (2), paroxetine (1),
and sertraline (1). The treatment period varied from 8 to 43 weeks with a mean of 14.7 (SD
11.3). However, when one outlier with 43 weeks was reduced to 10 weeks, the mean was
11.0 weeks. The proportion of patients reporting any side effects varied from 37% to 100% in
the drug conditions (mean 74.9, SD 22.1), and from 12.6% to 86.4% in the placebo conditions
(mean 55.3, SD 28.7). Finally, follow-up assessment was presented in only one study
(Neziroglu et al., 2000) with a period of 14 months.
14
Regarding blinding of participants there was a low risk in 4 (44%) and an unclear risk in 4
SRI-studies.
In order to score the risk of bias a low risk was given 1 point, an unclear risk 0.5, and a
high risk 0. The CBT-studies were scored on five variables and the SRI-studies on six. Thus,
the percentage of maximum score was calculated in order to compare the two groups of
studies. The mean score for CBT-studies (82.811.4) was significantly higher (t(32) = 4.43,
p<0.0001) than that of SRI-studies (64.87.1), which means that there was a lower risk of bias
in CBT-studies.
3.2.3. Specific methodological issues
3.2.3.1. Statistical power. Using a continuous variable, like CY-BOCS, and comparing two
conditions, as 85% of the studies do, the following cell sizes are needed to have 80% power
for an -level of .05: 26 if a large ES (d = 0.80), 64 if a medium (d = 0.50), and 400 if a small
ES (d = 0.20) is expected. A large majority (22, 65%) had a cell size which was <26, nine
(26%) had cell sizes of 26-63, and three (9%) had cell sizes of 64 or more. The mean cell size
at the start of the studies was 26.8 (SD 22.7).
When dividing the RCTs on primarily CBT- and SRI-studies we find that 28% of the
CBT- and 56% of the SRI-studies had cell sizes of 26, a non-significant difference (Fishers
test. two-tailed, p = 0.22).
3.2.3.2. Reliably diagnosing the participants. Of the 25 CBT-studies 22 (88%) used a
diagnostic schedule compared to 2 (22%) of the SRI-studies, a significant difference (Fishers
exact test, two-tailed, p = 0.0007). If the 5 studies directly comparing CBT and SRI are
excluded 100% of CBT-studies used interview schedules (Fishers exact test, p = 0.0001). Of
the 24 RCTs using an interview schedule only 4 (17%) reported IRR. Three of these (Barret
et al., 2004; Farrell et al., 2013; Lewin et al., 2014b) found perfect IRR (kappa-coefficient
1.0) and the forth (POTS, 2004) also had a high of 0.88.
15
3.2.3.3. Reliability of the primary outcome measure. The IRR of C-YBOCS should to be
demonstrated in each individual study by letting an independent rater blindly rerate a
proportion (e.g. 20%) of the interviews. Only 7 studies (21%) reported the IRR for their
application of CY-BOCS and the reliability coefficients varied between .81 and .98, with a
mean of .92. None of the SRI-studies reported IRR compared to seven (24%) of the CBTstudies, a non-significant difference (Fishers exact test, p = 0.149).
3.2.3.4. Independence and blindness of raters. Of the 34 studies in the current meta-analysis
21 (62%) reported having used independent assessors (IAs). In 10 studies (29%) it was
unclear whether the assessor was independent or not, and in two studies the assessors were
not independent. A total of 27 studies (79%) reported that the assessors were blind. When
independence and blindness were combined 20 (61%) of the studies had assessors who were
independent and blind, 2 (6%) had assessors who were neither, and 10 (30%) had unclear
independence/blindness status. Comparing CBT- and SRI-studies regarding proportion of
studies using independent assessors (54% and 89%, respectively) and blinded assessors (79%
and 89%, respectively) did not yield significant differences.
3.2.3.5. Adherence and competence ratings.
Adherence was assessed in 11 (44%) of the CBT-studies and competence in only 4
(16%) of the studies. Various rating scales were used for adherence and competence in these
studies and the reported means were recalculated as percentage of the scaless maximum
score. The mean for adherence was 89.6% and for competence 89.0%. The large proportion of
studies not assessing these important factors means that it is difficult to know if the patients
across the CBT-studies actually received the treatment they were supposed to get and how
competently it was delivered.
3.2.3.6. Credibility ratings. Fully 31 of the 34 studies (91%) were comparisons between two,
or more, active treatments. However, none of the studies included credibility ratings, and
16
only one (Lewin et al., 2014b) had expectancy ratings. This issue is particularly important
when it comes to studies using a placebo control condition. Thirteen of studies had a
condition with a psychological or pharmacological placebo but none assessed credibility.
3.2.3.7. Assessment of response and remission. Only 24 studies (71%) reported data on
response and 16 (47%) on remission. Three different criteria were used for treatment
response. Eleven studies used a certain percentage of reduction of the pre-treatment CYBOCS score. This varied from 25% (Asbahr et al., 2005) to 40% (Geller et al, 2001b), which
in CY-BOCS scores corresponded to 4.7 and 10.5 points, respectively. One study used the
cutoff score 15 (Skarphedinsson et al., 2015). The second most common criterion (11) was
a 1 or 2 on the Clinical Global Impression-Improvement scale. Finally, one study (Farrell et
al., 2013) used Reliable Change Index on CY-BOCS without any information of the required
change in points. Concerning remission 12 of the studies used a cutoff score on CY-BOCS
and of these the most common score was 10 (8), followed by 12 (3), and 14 (1). One
study used Clinically Significant Change on CY-BOCS (Farrell et al., 2013), and three
(Barrett et al., 2004; Bolton et al., 2008; Bolton et al., 2011) used free of OCD-diagnosis as
the remission criterion.
A comparison of CBT- and SRI-studies showed that there was no significant
difference regarding proportion of studies assessing response (68% for CBT and 78% for
SRI). However, 64% of the CBT-studies assessed remission, whereas none of the pure SRIstudies did so, a significant difference (Fishers exact test, two-tailed, p = 0.0011).
3.3. Meta-analysis
3.3.1. Attrition
A subgroup analysis of the attrition rates for the different conditions in this metaanalysis yielded a significant Qbetween (df 4) = 17.13, p = 0.002. The dropout rate was
17
significantly lower in CBT- (12.7%) than in SRI-conditions (23.5%) and placebo studies
(24.7%), but none of the other conditions differed significantly from each other. A
comparison within CBT studies yielded a significant Qbetween (df 2) = 8.52, p = 0.014. ERP
(17.8%) had a significantly higher attrition than CT (5.5%) and ERP+CT (9.9%), which did
not differ significantly.
3.3.2. Primary measure
Table 1 shows the results on CY-BOCS at post-treatment for all studies and divided
on the various types of comparisons. The overall ES was moderate (g = 0.52) but
significantly different from zero. It also had significant heterogeneity, which will be followed
up with moderator analyses (see 3.3.3.) All CBT- (g = 0.53) and all SRI-studies (g = 0.48)
had similar effect sizes, whereas combined CBT+SRI treatments (Combo) achieved a large
ES (g = 0.80). The latter was, however, based on only two studies. When dividing CBTstudies on different control groups we find that the effect size was very large for WLC- (g =
1.53) and large for placebo (g = 0.93) comparisons. The SRI vs. placebo comparison was
moderate (g = 0.51) but significant. When CBT was compared to any active treatment, SRIs,
Combo, or a different type of CBT the ESs were small and non-significant.
A sub-group analysis of type of CBT yielded a non-significant Qbetween (df 2) = 3.85, p
= 0.146. CT (k = 4) had a g = 1.04 (95% CI 0.45-1.63), ERP (k = 8) g = 0.68 (95% CI 0.181.18), and ERP+CT (k = 18) g = 0.35 (95% CI -0.04-0.73).
3.3.2.1. Placebo comparisons. A total of 14 studies included placebo control groups (SRI 9,
CBT 5). The overall ES for these studies (g = 0.68, 95% CI 0.46-0.90) was significantly
different from zero (z = 6.02, p = 0.0001) and significantly heterogeneous (Q = 36.5, I2 =
64%). A subgroup analysis using mixed effects found no significant difference (Qbetween =
2.65, p = 0.10) between SRI- (g = 0.52) and ERP-studies (g = 0.93).
18
3.3.2.2. SRI-studies. A sub-group analysis within the SRI-studies yielded a significant Qbetween
(df 4) = 9.98, p = 0.041). The different SRIs had the following ES: Clomipramine 1.12,
Fluoxetine 0.52, Paroxetine 0.52, Sertraline 0.28, and Fluvoxamine 0.05. However, there was
only one study each on Paroxetine and Sertraline. When these were deleted the difference
was still significant (Qbetween (df 2) = 6.50, p = 0.039).
3.3.2.3. Family-based CBT. There were a total of 10 family-based CBT (FCBT) comparisons
yielding a large ES (g = 0.92, 95% CI 0.32-1.52) which was significantly different from zero
(z = 3.02, p = 0.003) and heterogeneous (Q = 81.9, I2 = 89%). Subgroup analysis showed that
FCBT was significantly better than placebo (k = 4, g = 0.93) but not better than individual
CBT (k = 2, g = 0.24) in head-to-head comparisons (Peris & Piacentini, 2013; Reynolds et al.,
2013).
3.3.3. Moderator analyses
Continuous variables on which at least 75% of the studies provided information were
analyzed with the meta-regression module in the CMA program using the fixed effects
analysis (see Table 2). Mean age of the study sample was a negative moderator, i.e. lower ES
with increasing age. However, when the three studies which only had children in the age
range 3-8 were deleted from the analysis age was no longer a significant moderator. Pretreatment CY-BOCS score was also a significant negative moderator, i.e. lower ES with
increasing OCD severity. Analyzing this variable separately for CBT- and SRI-studies we
find opposite patterns; it was a negative moderator in CBT-studies but a positive moderator in
SRI-studies, i.e. higher ES with increasing OCD severity. Since the SRI-studies all have
placebo control we did a separate analysis with only placebo controlled CBT-studies and
found that pre-treatment CY-BOCS score was a positive moderator, i.e. the same result as for
SRI-studies. The methodological quality score of the CBT-studies was also a significant
positive predictor of ES. However, for SRI-studies methodological quality was a non-
19
significant negative moderator. Risk of bias was not a significant moderator, neither for all
studies, nor for CBT- and SRI-studies separately. Percent of eligible patients declining to
participate in the RCT was a negative moderator of ES. Of the remaining variables analyzed
weeks of treatment was a negative predictor, but this was entirely due to one outlier
(Neziroglu et al., 2000) with 43 weeks for the Combo treatment. When using the number of
weeks for the SRI condition in that study the moderator was no longer significant. Proportion
of females, of comorbidity, of patients on drug treatment for OCD during the CBT study,
treatment variables (for CBT), and attrition rate did not significantly moderate the ES.
However, the proportion of comorbid anxiety disorders was a positive moderator of ES.
For categorical variables sub-group analysis (mixed effects) in the CMA program was
used (see Table 3). The only variable that turned out significant was type of comparison group
with passive control (WLC) yielding significantly higher ES than active controls. However,
there was no difference between studies using ITT- or completer analysis. Within CBTstudies, treatment format, degree of parental involvement, and whether or not adherence to the
manual or therapist competence was assessed did not affect ES significantly.
3.3.4. Publication bias
The possibility of publication bias was investigated, using Duval and Tweedies trimand-fill method and Eggers regression intercept. For all studies, CBT studies, SRI studies,
and all the subsequent comparisons publication bias turned out not to be a problem. In 6 of the
9 comparisons no study was trimmed and in 3 only 1 study was trimmed. In no case was
Eggers regression intercept significant.
3.3.5. Response
The results regarding response to treatment are shown in Table 4. The subgroup
analysis yielded a significant Qbetween (df 4) = 70.40, p < 0.0001. CBT- (69.6%) and Combo(66.1%) had significantly higher response rates than SRI-conditions (48.9%), placebo
20
(29.3%), and WLC (13.0%). The response rate for SRI was significantly higher than that for
placebo and WLC, which did not differ from each other. A comparison within CBT-studies
yielded a significant Qbetween (df 1) = 6.44, p < 0.011; ERP+CT (77.8%) had a significantly
higher response rate than ERP (60.9%). A comparison within SRI-studies did not yield a
significant difference between clomipramine (56%) and SSRIs (48%).
At follow-up response data were provided by only 8 CBT-conditions, 2 Combo, and 1
SRI condition. The response rates were 79.7% for CBT, 69.5% for Combo, and 60.0% for
SRI, a non-significant difference (Qbetween (df 2) = 1.26, p = 0.53). Even if the follow-up
response rates are nominally higher than the post rates when post and follow-up response
rates were compared the sub-group analysis showed no significant differences for any of the
sub-groups.
3.3.6. Remission
Concerning remission (see Table 4) the sub-group analysis showed a significant
Qbetween (df 4) = 41.29, p < 0.0001. CBT- (52.7%) and Combo- (49.1%) had significantly
higher remission rates than SRI-conditions (24.1%), placebo (14.7%), and WLC (10.1%).
SRI, placebo, and WLC did not differ from each other on this measure. A comparison within
CBT-studies did not show a significant difference between ERP (46.8%), CT (54.1%), and
ERP+CT (55.3%).
At follow-up 11 CBT-conditions and only one Combo-condition provided remission
data. The remission rate was 66.3% for CBT and 69.2% for Combo. Sub-group analysis
comparing post and follow-up remission rates for CBT-conditions (k = 33) yielded a
significant Qbetween (df 1) = 6.38, p = 0.012), indicating that the remission rate increased from
post to follow-up assessment, approximately 9 months later.
3.3.7. Within-group effect size
21
The within-group effect sizes are shown in Table 5. For all conditions combined the
ESs was very large and significantly different from zero both at post-treatment (g = 1.35) and
follow-up (g = 2.66) assessment. The overall ES doubled from post to follow-up, which is
primarily due to the fact that placebo- and WLC-conditions are not included at follow-up
since they are treated after post-assessment. When post-treatment and follow-up ESs were
compared the difference was nonsignificant for CBT-conditions (Qbetween (df 1) = 1.05, p =
0.31), for SRI-conditions (Qbetween (df 1) = 0.06, p = 0.81), and for Combo conditions (Qbetween
(df 1) = 2.50, p = 0.11).
Sub-group analysis of the effect sizes at post-treatment yielded a significant Qbetween
(df 4) = 142.53, p < 0.0001. CBT (g = 2.43) and Combo (g = 2.54) had significantly higher
ES than SRI (g = 1.49), placebo (g = 0.84), and WLC (g = 0.22). The ES for SRI was
significantly higher than those of placebo and WLC, and placebo had a higher ES than WLC.
The sub-group analysis of follow-up ESs yielded a non-significant Qbetween (df 2) = 3.88, p =
0.144.
In order to evaluate if pre-treatment OCD-severity influenced the within-group ES
meta-regression analysis was used. For all CBT-conditions (k = 32) the point estimate of the
slope was positive and significant (z = 2.72, p = 0.0065) indicating larger ES as severity
increased. For the Combo conditions (k = 9) there was a significant negative point estimate
of the slope (z = -2.26, p = 0.024) indicating smaller ES as severity increased, whereas it was
negative but nonsignificant (z = -1.52, p = 0.13) for the SRI-conditions (k = 14).
4. Discussion
The aim of the present study was to provide an updated meta-analysis of the efficacy
of CBT and pharmacological treatment of pediatric OCD. This is the largest meta-analysis in
the field to date with 34 included RCTs, 25 of which were CBT- and 9 pure SRI-studies. The
22
results from the current study support findings from previous meta-analyses by demonstrating
that both CBT and SRI are efficacious interventions in the treatment of pediatric OCD.
23
CBT and SRIs reduce symptom severity, but it is noteworthy that the remission rate in SRIstudies was not significantly different from non-active treatment, and that 75% still met
diagnostic criteria for OCD post treatment.
For the CBT-studies we also investigated whether there was a difference in treatment
efficacy depending on the subtype of CBT applied. We found a larger ES for CT-studies than
for ERP and ERP+CT, but the difference was not significant and may be biased by a variety
of comparison conditions. When comparing family-based CBT and individual CBT we found
no significant difference, a finding consistent with that of McGuire et al. (2015). For the SRIstudies there was a significant difference in ES due to the type of drug. Clomipramine yielded
higher ES than the various SSRIs, which corroborates the finding reported by Snchez-Meca
et al. (2014).
4.2. Moderators
Some characteristics of the patient sample were found to be significant moderators of
treatment outcome; age, baseline severity, proportion declining participation, and proportion
of comorbid anxiety disorders. The significant association between age and ES was, however,
completely due to the three studies of very young patients (age 38); when excluding these
studies age no longer moderated ES. Further research on the youngest age group is necessary
to find out whether the relatively large effect sizes in these studies were caused merely by low
age or by other factors. Still, for the older children in the age range 818, the findings from
the current and previous meta-analyses (e.g. McGuire et al., 2015; Snchez-Meca et al., 2014)
indicate that age does not moderate outcome.
When analyzing all the studies together we found that pre-treatment OCD severity
moderated ES negatively, i.e. lower ES was associated with increasing severity. Separate
analyses showed that for the CBT-studies increasing severity was associated with lower ES,
24
but in the SRI-studies the effect was opposite. The use of different comparison conditions
explains this finding. Since all drug studies used placebo controls we analyzed CBT-studies
with placebo controls and for this subgroup there was a positive association between severity
and ES. McGuire et al. (2015) also included baseline OCD-severity as a potential moderator
but did not find a significant association. This may be due to the smaller number of
comparisons (10) compared to the present meta-analysis (34).
Further, when analyzing within-group ES for the CBT- conditions, we found that
higher pre-treatment severity yielded larger ES. This finding suggests that CBT is even more
effective in samples with severe OCD. The opposite effect was found for SRI and Combo
treatment; high severity at pre-treatment was associated with smaller effect sizes. However,
this finding should be interpreted with caution as the effect for SRI-studies was not significant
and for Combo studies it was based on only two studies.
Proportion of participants declining participation in the RCT was a significant
negative moderator for ES; the larger proportion of patients declining, the smaller the ES.
There are no obvious explanations for this finding and the issue is poorly investigated in
previous therapy research in general, and in the treatment of childhood OCD, in particular.
Our recent meta-analysis on CBT for adult OCD (st et al., 2015) did investigate proportion
of patients declining as a possible moderator but found no significant relationship between the
proportion of patients declining and ES.
Total proportion of comorbidity was not a significant moderator, but increasing
proportion of comorbid anxiety disorders was associated with larger ES. McGuire et al.
(2015) also found the same thing in CBT-studies with placebo as comparison. They suggest
that this finding may be explained by a more robust CBT response in OCD patients with
comorbid anxiety disorders as a result of a more fear-based psychopathology.
25
For CBT-studies higher methodological quality score was associated with higher ES.
This is important and indicates that it pays off to focus on designing a study with stringent
methodology. It runs counter to the meta-analysis on acceptance and commitment therapy by
st (2014) who found that the methodology score was a negative moderator, i.e. higher score
was associated with lower ES. For the SRI-studies in the present meta-analysis, we found that
methodological quality was not significantly associated with ES.
For CBT-studies the degree of parental involvement or treatment format (individual,
family or group) did not affect ES significantly. The results from the current study show that
CBT for pediatric OCD is effective when delivered in different formats, and that the active
involvement of parents is not a crucial factor for the treatment effects. This finding is
consistent with the findings of a meta-analysis on the effect of parental involvement in the
treatment of anxiety disorders overall by Thulin, Svirsky, Serlachius, Andersson, and st
(2014) who found no significant difference between parent-involved treatment and child-only
treatment, but a trend in favor of child-only.
26
disclosing the declining rate means that the samples in SRI-studies may be more highly
selective than CBT-samples since an unknown proportion of potential participants are not
included as they may prefer psychological treatment. Such a preference is illustrated by the
study of Lewin, McGuire, Murphy, and Storch (2014a).
27
28
29
The meta-analysis of Ivarsson et al. (2015) on SRI for OCD in children also concluded
that We find no support in the literature we reviewed that moderate to severe OCD should be
treated with COMBO from the start as recommended in the US AACAP parameter (p. 101).
Based on their results and ours CBT should be recommended as the first-line treatment
irrespective of comorbidity and pre-treatment severity.
4.7. Limitations
A meta-analysis is never better than the included studies and we cannot conclude how
effective CBT, SRI or Combo would be for patients not included in RCTs. It might me that
OCD-patients with the highest severity and certain types of comorbidities never apply for
treatment in a RCT and, thus, the treatments are not tested for these patients. Another
limitation of the current meta-analysis is the exclusion of RCTs not using the interviewversion of CY-BOCS (or Y-BOCS). However, only four studies were excluded for this
reason and it is unlikely that they would have changed the outcome had they been included.
A third limitation is that none of the SRI-studies provided data on remission and only one had
follow-up assessment. A final limitation is that multiple comparisons were done without
correction, since this is not included in the applied software.
30
degree of parental involvement in the therapy. Finally, the treatment effects are maintained or
furthered at follow-up.
Do a proper power analysis before starting a RCT and adjust the design accordingly.
The field does not learn much from underpowered RCTs yielding non-significant
differences on the primary outcome measures.
Use a proper random sequence generation and describe the concealment of allocation.
Videotape therapy sessions and assess therapists' adherence to the manual used and
their competence in carrying out the treatment.
Use three (or more) therapists with proper training and randomize patients, not only to
condition, but also to therapist in order to enable analysis of therapist effect.
31
Funding
No external funding was obtained for this meta-analysis.
Contributors
LG designed the meta-analysis, wrote the coding schema, rated the studies, meta-analyzed
the included studies, and wrote the first draft of method and results. ENR did the literature
search, coded the studies, and wrote the first draft of introduction and discussion. GJW did the
literature search, rated the SRI-studies, and co-rated the CBT-studies. BH and GK co-wrote
the first draft of introduction and discussion with ENR. All authors participated in the revision
and approved the final manuscript.
Conflict of interest
None of the authors have any conflict of interest to report.
References
* Indicates studies included in the meta-analysis.
AACAP. (2012). Practice parameter for the assessment and treatment of children and
adolescents with obsessive-compulsive disorder. Journal of the American Academy of
Child & Adolescent Psychiatry, 51(1), 98-113. doi.org/10.1016/j.jaac.2011.09.019
Abramowitz, J. S., Whiteside, S. P., & Deacon, B. J. (2005). The effectiveness of treatment
for pediatric obsessive-compulsive disorder: A meta-analysis. Behavior Therapy,
36(1), 55-63. doi.org/10.1016/S0005-7894(05)80054-1
*Asbahr, F. R., Castillo, A. R., Ito, L. M., Latorre, M. R. D. d. O., Moreira, M. N., & LotufoNeto, F. (2005). Group cognitive-behavioral therapy versus sertraline for the treatment
of children and adolescents with obsessive-compulsive disorder. Journal of the
American Academy of Child & Adolescent Psychiatry, 44(11), 1128-1136.
doi.org/10.1097/01.chi.0000177324.40005.6f
*Barrett, P., Healy-Farrell, L., & March, J. S. (2004). Cognitive-behavioral family treatment
of childhood obsessive-compulsive disorder: A controlled trial. Journal of the
American Academy of Child & Adolescent Psychiatry, 43(1), 46-62.
doi.org/10.1097/00004583-200401000-00014
Biostat Inc. (2006). Comprehensive Meta-Analysis, version 2. Statistical software.
Englewood, NJ: Biostat Inc.
32
*Bolton, D., & Perrin, S. (2008). Evaluation of exposure with response-prevention for
obsessive compulsive disorder in childhood and adolescence. Journal of Behavior
Therapy and Experimental Psychiatry, 39, 11-22. doi.org/10.1016/j.jbtep.2006.11.002
*Bolton, D., Williams, T., Perrin, S., Atkinson, L., Gallop, C., Waite, P., & Salkovskis, P.
(2011). Randomized controlled trial of full and brief cognitive-behaviour therapy and
wait-list for paediatric obsessive-compulsive disorder. Journal of Child Psychology
and Psychiatry, 52, 1269-1278. doi.org/10.1111/j.1469-7610.2011.02419.x
Canals, J., Hernndez-Martnez, C., Cosi, S., & Voltas, N. (2012). The epidemiology of
obsessivecompulsive disorder in Spanish school children. Journal of Anxiety
Disorders, 26(7), 746-752. doi.org/10.1016/j.janxdis.2012.06.003
*de Haan, E., Hoogduin, K. A., Buitelaar, J. K., & Keijsers, G. P. (1998). Behavior therapy
versus clomipramine for the treatment of obsessive-compulsive disorder in children
and adolescents. Journal of the American Academy of Child & Adolescent Psychiatry,
37(10), 1022-1029. doi.org/10.1097/00004583-199810000-00011
*DeVeaugh-Geiss, J., Moroz, G., Biederman, J., Cantwell, D., Fontaine, R., Greist,
Landau, P. (1992). Clomipramine hydrochloride in childhood and adolescent
obsessive-compulsive disorder - a multicenter trial. Journal of the American Academy
of Child and Adolescent Psychiatry, 31, 45-49. doi.org/10.1097/00004583199201000-00008
Duval, S., & Tweedie, R. (2000). Trim and fill: A simple funnel-plot-based method of testing
and adjusting for publication bias in meta-analysis. Biometrics, 56(2), 455-463.
doi.org/10.1111/j.0006-341X.2000.00455.x.
Egger, M., Davey Smith, G., Schneider, M., & Minder, C. (1997). Bias in meta-analysis
detected by a simple, graphical test. British Medical Journal, 315(7109), 629-634.
doi.org/10.1136/bmj.316.7129.469.
*Farrell, L. J., Waters, A. M., Boschen, M. J., Hattingh, L., McConnell, H., Milliner, E. L.,
Storch, E. A. (2013). Difficult-to-treat pediatric obsessive-compulsive disorder:
feasibility and preliminary results of a randomized pilot trial of D-cycloserineaugmented behavior therapy. Depression and Anxiety, 30, 723-731.
doi.org/10.1002/da.22132
*Franklin, M. E., Sapyta, J., Freeman, J. B., Khanna, M., Compton, S., Almirall, D.,
March, J. S. (2011). Cognitive behavior therapy augmentation of pharmacotherapy in
pediatric obsessive-compulsive disorder: The pediatric OCD treatment study II (POTS
II) randomized controlled trial. JAMA. 306, 1224-1232.
doi.org/10.1001/jama.2011.1344.
Freeman, J. B., Choate-Summers, M. L., Moore, P. S., Garcia, A. M., Sapyta, J. J., Leonard,
H. L., & Franklin, M. E. (2007). Cognitive behavioral treatment for young children
with obsessive-compulsive disorder. Biological Psychiatry, 61(3), 337-343.
doi.org/10.1016/j.biopsych.2006.12.015
*Freeman, J. B., Garcia, A. M., Coyne, L., Ale, C., Przeworski, A. M. Y., Himle, M., . . .
Leonard, H. L. (2008). Early childhood OCD: preliminary findings from a familybased cognitive-behavioral approach. Journal of the American Academy of Child &
Adolescent Psychiatry, 47(5), 593-602. doi.org/10.1097/CHI.0b013e31816765f9
*Freeman, J., Sapyta, J., Garcia, A., Compton, S., Khanna, M., Flessner, C., . . . Franklin, M.
(2014). Family-based treatment of early childhood obsessive-compulsive disorder: the
pediatric obsessive-compulsive disorder treatment study for young children (POTS
Jr)-a randomized clinical trial.(Report). JAMA Psychiatry, 71(6), 689-698.
doi.org/10.1001/jamapsychiatry.2014.170.
Geller, D., Biederman, J., Faraone, S. V., Frazier, J., Coffey, B. J., Kim, G., & Bellordre, C.
A. (2000). Clinical correlates of obsessive compulsive disorder in children and
33
*March, J. S., Johnston, H., Jefferson, J. W., Kobak, K. A., & Greist, J. H. (1990). Do subtle
neurological impairments predict treatment resistance to clomipramine in children and
adolescents with obsessive-compulsive disorder? Journal of Child and Adolescent
Psychopharmacology, 1, 133-140. doi.org/10.1089/cap.1990.1.133
*March, J. S., Biederman, J., Wolkow, R., Safferman, A., Mardekian, J., Cook, E. H.,
Wagner, K. D. (1998). Sertraline in children and adolescents with obsessivecompulsive disorder: A multicenter randomized controlled trial. JAMA, 280, 17521756. doi.org/10.1001/jama.280.20.1752
Mataix-Cols, D., Fernandez de la Cruz, L., Nordsleten, A. E., Lenhard, F., Isomura, K., &
Simpson, H. B. (2016). Towards an international expert consensus for defining
treatment response, remission, recovery, and relapse in obsessive-compulsive disorder:
A Delphi survey. World Psychiatry, in press.
*Mataix-Cols, D., Turner, C., Monzani, B., Isomura, K., Murphy, C., Krebs, G., & Heyman,
I. (2014). Cognitive-behavioural therapy with post-session D-cycloserine
augmentation for paediatric obsessive-compulsive disorder: pilot randomised
controlled trial. British Journal of Psychiatry, 204(1), 77.
doi.org/10.1192/bjp.bp.113.126284
McGuire, J. F., Piacentini, J., Lewin, A. B., Brennan, E. A., Murphy, T. K., & Storch, E. A.
(2015). A meta-analysis of cognitive behavior therapy and medication for child
obsessive-compulsive disorder: moderators of treatment efficacy, response, and
remission. Depression and Anxiety, 32(8), 580-593. doi.org/10.1002/da.22389
*Merlo, L. J., Storch, E. A., Lehmkuhl, H. D., Jacob, M. L., Murphy, T. K., Goodman, W. K.,
& Geffken, G. R. (2010). Cognitive behavioral therapy plus motivational interviewing
improves outcome for pediatric obsessive-compulsive disorder: A preliminary study.
Cognitive Behaviour Therapy, 39, 24-27. doi.org/10.1080/16506070902831773
Micali, N., Heyman, I., Perez, M., Hilton, K., Nakatani, E., Turner, C., & Mataix-Cols, D.
(2010). Long-term outcomes of obsessive-compulsive disorder: follow-up of 142
children and adolescents. British Journal of Psychiatry, 197(2), 128-134.
doi.org/10.1192/bjp.bp.109.075317
Moncrieff, J., Churchill, R., Drummond, D. C., & McGuire, H. (2001). Development of a
quality assessment instrument for trials of treatments for depression and neurosis.
International Journal of Methods in Psychiatric Research, 10(3), 126-133.
doi.org/10.1002/mpr.108
Morris, S.B., & DeShon, R.P. (2002). Combining effect size estimates inmeta-analysis with
repeated measures and independent-groups designs. Psychological Methods, 7(1),
105125. doi.org/10.1037/1082-989X.7.1.105.
*Neziroglu, F., Yaryura-Tobias, J. A., Walz, J., & McKay, D. (2000). The effect of
fluvoxamine and behavior therapy on children and adolescents with obsessivecompulsive disorder. Journal of Child and Adolescent Psychopharmacology, 10(4),
295-306. doi.org/10.1089/cap.2000.10.295
NICE. (2005). Obsessive-compulsive disorder: Core interventions in the treatment of
obsessive-compulsive disorder and body dysmorphic disorder. Retrieved from
https://www.nice.org.uk/guidance/cg31
O'Kearney, R. T., Anstey, K. J., Von Sanden, C. & Hunt, A.(2006). Behavioural and
cognitive behavioural therapy for obsessive compulsive disorder in children and
adolescents. Cochrane database of systematic reviews(4), CD004856.
doi.org/10.1002/14651858.CD004856.pub2
st, L.-G. (2008). Efficacy of the third wave of behavioral therapies: A systematic review and
meta-analysis. Behaviour Research and Therapy, 46(3), 296-321.
doi.org/10.1016/j.brat.2007.12.005
35
Skarphedinsson, G., Hanssen-Bauer, K., Kornr, H., Heiervang, E. R., Landr, N. I.,
Axelsdottir, B., . . . Ivarsson, T. (2014). Standard individual cognitive behaviour
therapy for paediatric obsessivecompulsive disorder: A systematic review of effect
estimates across comparisons. Nordic Journal of Psychiatry, 69(2), 81-92.
doi.org/10.3109/08039488.2014.941395
*Skarphedinsson, G., Weidle, B., Thomsen, P., Dahl, K., Torp, N., Nissen, J., . . . Ivarsson, T.
(2015). Continued cognitive-behavior therapy versus sertraline for children and
adolescents with obsessivecompulsive disorder that were non-responders to
cognitive-behavior therapy: a randomized controlled trial. European Child &
Adolescent Psychiatry, 24(5), 591-602. doi.org/10.1007/s00787-014-0613-0
Stewart, S. E., Geller, D. A., Jenike, M., Pauls, D., Shaw, D., Mullin, B., & Faraone, S. V.
(2004). Long-term outcome of pediatric obsessive-compulsive disorder: a metaanalysis and qualitative review of the literature. Acta Psychiatrica Scandinavica,
110(1), 4-13. doi.org/10.1111/j.1600-0447.2004.00302.x
*Storch, E. A., Bussing, R., Small, B. J., Geffken, G. R., McNamara, J. P., Rahman, O.,
Murphy, T. K. (2013). Randomized, placebo-controlled trial of cognitive-behavioral
therapy alone or combined with sertraline in the treatment of pediatric obsessivecompulsive disorder. Behaviour Research and Therapy, 51, 823-829.
doi.org/10.1016/j.brat.2013.09.007
*Storch, E. A., Caporino, N. E., Morgan, J. R., Lewin, A. B., Rojas, A., Brauer, L.,
Murphy, T. K. (2011). Preliminary investigation of web-camera delivered cognitivebehavioral therapy for youth with obsessive-compulsive disorder. Psychiatry
Research, 189(3), 407-412. doi.org/10.1016/j.psychres.2011.05.047
*Storch, E. A., Geffken, G. R., Merlo, L. J., Mann, G., Duke, D., Munson, M., . . . Goodman,
W. K. (2007). Family-based cognitive-behavioral therapy for pediatric obsessivecompulsive disorder: Comparison of intensive and weekly approaches. Journal of the
American Academy of Child & Adolescent Psychiatry, 46(4), 469-478.
doi.org/10.1097/chi.0b013e31803062e7
*Storch, E. A., Murphy, T. K., Goodman, W. K., Geffken, G. R., Lewin, A. B., Henin, A.,
Geller, D. A. (2010). A preliminary study of d-cycloserine augmentation of cognitivebehavioral therapy in pediatric obsessive-compulsive disorder. Biological Psychiatry,
68(11), 1073-1076. doi.org/10.1016/j.biopsych.2010.07.015
Thulin, U., Svirsky, L., Serlachius, E., Andersson, G., & st, L.-G. (2014). The effect of
parent involvement in the treatment of anxiety disorders in children: A meta-analysis.
Cognitive Behaviour Therapy, 43(3), 185-200.
doi.org/10.1080/16506073.2014.923928
*Turner, C. M., Mataix-Cols, D., Lovell, K., Krebs, G., Lang, K., Byford, S., & Heyman, I.
(2014). Telephone cognitive-behavioral therapy for adolescents with obsessivecompulsive disorder: A randomized controlled non-inferiority trial. Journal of the
American Academy of Child & Adolescent Psychiatry, 53(12), 1298-1307.
doi.org/10.1016/j.jaac.2014.09.012
Watson, H. J., & Rees, C. S. (2008). Meta-analysis of randomized, controlled treatment trials
for pediatric obsessive-compulsive disorder. Journal of Child Psychology and
Psychiatry, 49(5), 489-498. doi.org/10.1111/j.1469-7610.2007.01875.x
*Williams, T. I., Salkovskis, P. M., Forrester, L., Turner, S., White, H., & Allsopp, M. A.
(2010). A randomised controlled trial of cognitive behavioural treatment for obsessive
compulsive disorder in children and adolescents. European Child & Adolescent
Psychiatry, 19, 449-456. doi.org/10.1007/s00787-009-0077-9
37
38
References identified by
literature search: 674
Included: 34 RCTs
39
Table 1
Effect sizes (Hedges g) on CY-BOCS for all OCD RCTs and divided on comparison conditions for posttreatment assessments.
Q-value
I2
5.31d
192.7d
78
0.25-0.80
3.74d
174.7d
83
0.48
0.26-0.70
4.36d
14.1
43
0.80
0.48-1.11
4.97d
0.3
23
0.21
-0.03-0.45
1.71
74.3d
70
0.22
-0.08-0.52
1.46
4.7
15
-0.14
-0.41-0.14
-0.97
4.0
0.03
-0.27-0.32
0.16
12.2
43
0.93
0.47-1.38
3.96d
13.6b
71
1.53
0.95-2.10
5.22d
27.1
78
0.51
0.31-0.71
4.98d
10.9
36
Comparison
g-value
95% CI
All studies
42
0.52
0.33-0.72
All CBT
30
0.53
All SRI
Combo
CBT vs. active Tx
z-value
________________________________________________________________________________________
Note: k = number of comparisons. A positive g-value means that the first treatment in the comparison is better
a
b
c
d
and a negative that the second is better. p<0.05, p<0.01, p<0.001, p<0.0001
40
Table 2
Moderator analyses of the overall effect size of OCD RCTs at post-treatment.
Variable
Point est.
34
-0.0098 -4.01
31
0.0012
34
z-value
p-value
0.001
0.31
0.759
-0.0064 -2.26
0.024
25
-0.0187
-5.36
0.001
0.0280
2.46
0.014
SRI-studies
0.0160
2.89
0.004
25
CBT-studies
CBT vs. placebo
0.0573 3.30
0.001
-0.0086 -0.45
0.653
34
0.0038 1.16
0.245
-0.0011 -3.91
0.001
Percent females
33
0.0054 0.90
0.367
29
0.0034 1.83
0.067
27
0.0076
24
0.0007 0.43
0.667
Weeks of treatment
34
-0.0254 -1.95
0.051
33
-0.0166
25
0.0087 0.22
1 outlier modified
3.90
-1.03
0.302
0.825
25
-0.0015 -1.08
0.281
Intensity (CBT)
25
-0.0098 -1.38
0.167
Attrition total
0.001
34
-0.0005 -1.31
0.189
Attrition primary Tx
34
-0.0005 -1.19
0.233
Attrition comparison
34
-0.0005 -1.34
0.179
41
Table 3
Subgroup analyses of the overall effect size of OCD RCTs at post-treatment.
Variable
95% CI
Type of comparison
Active treatment
Passive control 9
33
1.21
0.36
0.18-0.53
0.61-1.81
4
38
0.53
0.52
0.08-0.99
0.31-0.72
20
9
0.42
0.72
0.15-0.68
0.12-1.32
0.78
0.40
0.66
0.40-1.17
0.05-0.76
0.03-1.28
0.65
0.48
0.14-1.16
0.22-0.74
Qb-value
p-value
7.17
0.007
0.00
0.961
0.81
0.369
2.06
0.356
0.33
0.566
42
Table 4
Proportions of response and remission at post-treatment.
Comparison
Mea-
sure
CBT
SRI
CBT+SRI
Placebo
WLC
Propor-
95% CI
z-value*
Q-value
I2
tion
Resp.
20
69.6%
61.7-76.5
4.64d
37.6b
50
Rem.
22
52.7%
46.0-59.3
0.80
41.3b
49
Resp.
12
48.9%
40.7-57.1
-0.27
30.1b
63
Rem.
24.1%
14.2-37.9
-3.45c
0.2
Resp.
66.1%
56.1-74.9
3.09b
2.6
Rem.
49.1%
31.8-66.6
-0.10
8.5
53
Resp.
10
29.3%
23.5-35.9
-5.74d
16.4
45
Rem.
14.7%
7.2-27.9
-4.26d
3.2
Resp.
13.0%
3.3-39.7
-2.51a
0.3
Rem.
10.1%
3.8-24.0
-4.15d
1.0
_______________________________________________________________________________________
Note: k = number of comparisons, *Test if significantly different from 50%, Resp. = response, Rem. = remission.
a
b
c
d
p<0.05, p<0.01, p<0.001, p<0.0001.
43
Table 5
Within-group effect sizes (Hedges g) for all treatment conditions at post-treatment and follow-up
assessments.
k
g-value
95% CI
z-value
Q-value
I2
Post
74
1.35
1.24-1.47
23.18d
611.2d
88
F-up
24
2.66
2.31-3.01
14.75d
62.7d
80
Post
32
2.43
2.17-2.69
18.28d
87.7d
66
F-up
20
2.68
2.29-3.06
13.72d
53.6d
65
Post
16
1.50
1.30-1.70
15.04d
33.0b
58
F-up
1.71
0.44-2.98
2.64b
Post
2.54
1.87-3.22
7.39d
26.4d
73
F-up
3.58
2.21-4.94
5.13d
3.5
43
Placebo*
Post
13
0.84
0.64-1.03
8.22d
39.7b
70
WLC*
Post
0.22
-0.13-0.57
1.22
10.1a
60
Comparison
Time
point
All conditions
CBT
SRI
Comb.
________________________________________________________________________________________
a
b
c
d
Note: k = number of comparisons, p<0.05, p<0.0001, p<0.0001, p<0.0001, * No follow-up assessment.
44