• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

Evidence Table 7Obsessive-compulsive Disorder

STUDY:Authors: Ackerman, et al.135
Year: 2002
Country: US
FUNDING:NIMH
DESIGN:Study design: Meta-analysis (meta regression)
AIMS OF REVIEW:Meta-analysis with meta regression for treatment of OCD to explain the apparent discrepancy in the literature that makes it seem that CMI is superior to SSRI’s in placebo trials vs. in head/head comparison
STUDIES INCLUDED IN META- ANALYSISGoodman et al., 1989, Jenike et al., 1990, Mallya et al., 1992, Goodman et al., 1996, Montgomery et al., 1993, Tollefson et al., 1994, Chouinard et al., 1990, Greist et al., 1995, Kronig et al., 1999, Zohar and Judge, 1996
TIME PERIOD COVERED:Not explicitly reported, studies included spanned 1992–1997 for head to head comparisons and 1989–1999 for placebo comparisons
CHARACTERISTICS OF INCLUDED STUDIES:RCTs, double-blinded; 8 weeks or longer; efficacy assessed with Y-BOCS; point estimates and SD(or SE) provided or calculable from report
CHARACTERISTICS OF INCLUDED POPULATIONS:Not reported
CHARACTERISTICS OF INCLUDED INTERVENTIONS:Clomipramine, fluvoxamine, fluoxetine, sertraline, paroxetine, placebo
MAIN RESULTS:
  • Result reported as mean difference in change from baseline on Y-BOCS scale support equal efficacy for clomipramine and all SSRIs; pooled difference between clomipramine and all SSRIs was 0.15 (95% CI −8.86, 9.16), where a number significantly greater than 1.00 would represent greater efficacy for the SSRIs
  • Effect size was estimated as the difference in improvement (decrease in Y-BOCS) between active drug and placebo. Negative pooled difference represents greater improvement (greater decrease in Y-BOCS) across studies for the active drug compared to placebo
  • Pooled Difference:
    • Fluvoxamine vs. placebo (4 studies): −4.84 (−7.78, −1.83)
    • Fluoxetine vs. placebo (3 studies): −1.61 (−2.18, −1.04)
    • Sertraline vs. placebo (4 studies): −2.47 (−6.13, 1.20)
    • Paroxetine vs. placebo (1 study): −3.00 (−4.91, −1.09)
ADVERSE EVENTS:None reported
COMPREHENSIVE LITERATURE SEARCH STRATEGY:Yes
STANDARD METHOD OF APPRAISAL OF STUDIES:No
QUALITY RATING:Fair
STUDY:Authors: Bergeron, et al.136
Year: 2002
Country: Canada
FUNDING:Pfizer
DESIGN:Study design: RCT
Setting: Multi-center
Sample size: 150
INTERVENTION:
Drug:SertralineFluoxetine
Dose:50–200 mg/d20–80 mg/d
Duration:24 weeks24 weeks
INCLUSION:Ages 18–65; primary diagnosis of OCD for at least 6 months using Structured Clinical Interview based on DSM-IV criteria; baseline minimum scores of ≥ 17 on Y-BOCS; ≥ 7 on NIMH-OC; and CGI-S ≥ 4 and HAM-D17 ≤ 17; females had to have negative pregnancy test at baseline and using medically acceptable form of contraception for at least 3 months
EXCLUSION:Primary Axis I disorder other than OCD including presence of major depressive episode; >25% reduction in Y-BOCS or NIMH-OC or > 2 point improvement in CGI-S during washout; suicidal; history of seizure disorder; organic brain disorder; anorexia; bulimia; purgative abuse; drug or alcohol abuse or dependence within 6 months prior; psychotropic medication within the previous week; 2 weeks for antidepressants requiring concomitant treatment with any psychotropic (other than exception as previously noted); requiring concurrent ECT, cognitive-behavioral therapy or formal structured psychotherapy or a likelihood that such therapy might be required; acute or unstable medical condition or used any meds known to interact with either study drug; reported previous adequate treatment > 4 weeks with either study drug or known or suspected intolerance or allergy; participated in a clinical research study within the prior 4 months; pregnancy or lactation
OTHER MEDICATIONS/ INTERVENTIONS:Zopiclone or chloral hydrate as hypnotics
POPULATION CHARACTERISTICS:Groups similar at baseline: Not reported
Mean age: 36; sertraline: 36.6; fluoxetine: 36.5
Gender (female%): 54%
Ethnicity: Not reported
Other population characteristics: Approximately 20% of the sample had a history of a prior episode of depression; OCD > 10 years in 79% of patients
OUTCOME ASSESSMENT:Measures: Primary efficacy measures: Y-BOCS, NIMH-OC, CGI-S, response (CGI-I ≤ 2), remission (CGI-I ≤ 2 and YBOCS ≤ 11); Secondary measures: HAM-D, CAS, Yale schedule for multiple tics and tourettes, Battelle QOL

Timing of assessments: Screening, baseline, weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 or final visit if patients withdrew before study end
RESULTS:
  • No significant differences in mean Y-BOCS change at endpoint
  • Sertraline showed statistically significant improvement at some of the early assessment times (weeks 4, 8, 12)
  • No difference in CGI-S or CGI-I between groups at week 24
  • Median time to response not significantly different
    • Sertraline: 16 weeks
    • Fluoxetine: 20 weeks (p = 0.703)
  • Remission (combined CGI and YBOCS):
    • Week 12: Sertraline: 20%, Fluoxetine: 8% (p = 0.045)
    • Week 24: Sertraline: 36%, Fluoxetine: 22% (p = 0.075)
ANALYSIS:ITT: Yes
Post randomization exclusions: Yes
ATTRITION:Loss to follow-up: 29.3%; sertraline: 29%; fluoxetine: 30%
Withdrawals due to adverse events: Sertraline: 19%; fluoxetine: 14% (p = 0.342)
Loss to follow-up differential high: No
ADVERSE EVENTS:
  • No significant differences in incidence of side effects between groups
  • Effects with a 5% or more difference between groups (no p-values given): nausea: sertraline: 41%, fluoxetine: 28%; fatigue: sertraline: 28%, fluoxetine: 22%; flu-like symptoms: sertraline: 25% fluoxetine: 19%; dyspepsia: sertraline: 24%, fluoxetine: 17%; tremor: sertraline: 12%, fluoxetine: 4%; somnolence: sertraline: 13%, fluoxetine: 21%
  • No significant differences in body weight change between groups
QUALITY RATING:Fair
STUDY:Authors: Denys D, et al.137, 138
Year: 2003
Country: US
FUNDING:Wyeth and Glaxo-Smith-Kline
DESIGN:Study design: RCT
Setting: Single center
Sample size: 150
INTERVENTION:
Drug:VenlafaxineParoxetine
Dose:75–300 mg/d15–60 mg/d
Duration:12 weeks12 weeks
INCLUSION:DSM-IV criteria for OCD; ≥ 18 on the Y-BOCS or ≥ 12 if only obsessions or compulsions were present; 18–65 years of age
EXCLUSION:Organic mental disorders; epilepsy; CNS disorder; DSM-IV diagnosis of major depression; psychotic illness or bipolar disorder; personality disorder; severe somatic symptoms; pregnancy; suicidal; use of antidepressants 1 month before study
OTHER MEDICATIONS/INTERVENTIONS:Oxazepam, maximum of 30 mg/d, was permitted on an intermittent basis
POPULATION CHARACTERISTICS:Groups similar at baseline: Yes
Mean age: 35; venlafaxine: 36, paroxetine: 34
Gender (female%): venlafaxine: 63%, paroxetine: 61%
Ethnicity: Not reported
Other population characteristics: Patients assigned to venlafaxine had a significantly greater number of previous medication trials
OUTCOME ASSESSMENT:Measures: Yale-Brown Obsessive Compulsive scale (Y-BOCS), Hamilton Anxiety Scale (HAS), HAM-D-17, Global Assessment of Functioning, Lancashire Quality of Life Profile (LQoLP)
Timing of assessments: Baseline, weeks 1, 3, 5, 8, 10, 12
RESULTS:
  • Paroxetine showed significantly greater improvement in HAM-D at endpoint (p < 0.05)
  • Both treatment groups had a significant improvement in Y-BOCS score but there was no significant difference between treatment groups; no differences in HAS
  • Paroxetine and venlafaxine groups improved on all QoL measures
  • Paroxetine and venlafaxine were equally effective based on LQoLP improvement scores
ANALYSIS:ITT: Yes
Post randomization exclusions: Yes
ATTRITION:Loss to follow-up: 16 (11%)
Withdrawals due to adverse events: 5%; venlafaxine: 2%, paroxetine: 6%
Loss to follow-up differential high: No
ADVERSE EVENTS:
  • Somnolence, sweating, insomnia, nausea, dry mouth, dizziness, constipation, sexual dysfunction
  • No differences reported
QUALITY RATING:Fair
STUDY:Authors: Denys D, et al.139
Year: 2004
Country: The Netherlands
FUNDING:Wyeth and GlaxoSmithKline
DESIGN:Study design: RCT
Setting: Single center
Sample size: 43 (of 150) continued in switch study
INTERVENTION:
Drug:ParoxetineVenlafaxine XR
Dose:60 mg/d300 mg/d
Duration:12 weeks (switch study)12 weeks (switch study)
Sample Size:2716
INCLUSION:Outpatients ages 18–65 with a primary OCD according to DSM-IV criteria; only patients with a score of at least 18 on the Y-BOCS or at least 12 if only obsessions or compulsions were included; nonresponse in the first phase of the study defined as less than a 25% decrease in Y-BOCS
EXCLUSION:Patients with significant depression as determined by a total score of 15 or more on the HAM-D on admission were excluded; pregnant women, childbearing potential not using adequate methods of contraception; patients with organic mental disorders, epilepsy, any structural central nervous system disorder or stroke within the last year; primary DSM–IV diagnoses of major depression, bipolar disorder, schizophrenia, or any other psychotic condition; substance-related disorders within the past 6 months; primary anxiety disorders or obvious personality disorders; use of antidepressants or antipsychotics 1 month before screening visit; use of a concomitant psychotropic drug, behavioral or cognitive therapy 3 months prior to the screening visit
OTHER MEDICATIONS/ INTERVENTIONS:Not reported
POPULATION CHARACTERISTICS:Groups similar at baseline: Yes
Mean age: 35
Gender (% female): 54.5%
Ethnicity: Not reported
Other population characteristics: YBOCS total score 27.7; HAM-A score 11.0; HAM-D score 7.6
OUTCOME ASSESSMENT:Measures: Y-BOCS; HAM-D; HAM-A; GAF
Timing of assessments: 0, 1, 3, 5, 8, 10, 12 weeks
RESULTS:
  • LOCF analysis demonstrated a mean decrease of 1.8 (+/−3.5) in the venlafaxine XR group and 6.5 (+/−7.1) in the paroxetine group as measured by the reduction in total Y-BOCS scores; significant decrease in total Y-BOCS score from baseline was found in the paroxetine group (t=4.7, df=26, p < 0.0001) but not in the venlafaxine group (t = 2.0, df = 15, p = .065)
  • No significant differences between baseline and endpoint for venlafaxine XR- or paroxetine-treated patients on the HAM-D or HAM-A
  • GAF not reported
ANALYSIS:ITT: Yes
Post randomization exclusions: Not reported
ATTRITION:Loss to follow-up: Paroxetine 0 (0%); Venlafaxine XR 1 (6%) (numbers reported for 43 patients switching)
Withdrawals due to adverse events: Yes
Loss to follow-up differential high: No
ADVERSE EVENTS:
  • 98% of patients reported adverse events;
  • Paroxetine: somnolence 54%, sweating 25%, headache 21%, constipation 21%, insomnia 18%, nausea 18%, change in mood 18%, loss of libido 18%
  • Venlafaxine: somnolence 38%, sweating 31%, constipation 31%, dry mouth 19%, headache 13%, insomnia 13%, nausea 13%, loss of libido 13%
  • p-values not reported
QUALITY RATING:Fair
STUDY:Authors: Montgomery SA, et. al.140
Year: 2001
Country: Europe, South Africa
FUNDING:Lundbeck A/S
DESIGN:Study design: RCT
Setting: Multi-center
Sample size: 401
INTERVENTION:
Drug:CitalopramCitalopramCitalopramPlacebo
Dose:20 mg/d40 mg/d60 mg/dN/A
Duration:12 weeks12 weeks12 weeks12 weeks
INCLUSION:18–65 years; DSM-IV criteria for OCD; Y-BOCS ≥ 20; symptoms stable for the preceding 6 months
EXCLUSION:MADRS ≥ 22; other Axis I disorders; suicidal risk; recent treatment with fluoxetine or MAOI; hypersensitivity to SSRIs; hepatic impairment; drug/alcohol dependence; pregnancy/lactation; Tourette’s syndrome in family; concomitant therapy with anticonvulsive and psychoactive drugs
OTHER MEDICATIONS/ INTERVENTIONS:55.4% received concomitant medication
POPULATION CHARACTERISTICS:Groups similar at baseline: Yes
Mean Age: 38; citalopram: 37.6, placebo: 38.6
Gender (% female): citalopram: 55%, placebo: 50.1%
Ethnicity: Not reported
Other population characteristics: Mean duration of illness greater than 15 years for all groups
OUTCOME ASSESSMENT:Measures: Y-BOCS, MADRS, CGI-I, NIMH-OC
Timing of assessments: Baseline, weeks 1, 3, 5, 7, 9, 12
RESULTS:
  • A significant reduction in Y-BOCS scores for all 3 citalopram groups (p < 0.01) compared to placebo
  • Citalopram 60 mg reached statistical significance at week 3, citalopram 20 mg and 40 mg at week 7
  • Changes in NIMH-OC scores were also significantly greater in the citalopram groups (p < 0.001)
  • All 3 treatment groups had significantly more responders than placebo
ANALYSIS:ITT: Yes
Post randomization exclusions: Not reported
ATTRITION:Loss to follow-up: 16%; citalopram 20 mg: 16%; citalopram 40 mg: 15%; citalopram 60 mg: 15%; placebo: 17%
Withdrawals due to adverse events: 4%; citalopram 20 mg: 4%; citalopram 40 mg: 6%; citalopram 60 mg: 4%; placebo: 2%
Loss to follow-up differential high: No
ADVERSE EVENTS:
  • Treatment emergent adverse events: citalopram 20 mg: 73%; citalopram 40 mg: 68%; citalopram 60 mg: 72%; placebo: 58%
  • The incidence of nausea, insomnia, fatigue, increased sweating, dry mouth, ejaculation failure, and diarrhea was significantly higher in one or more citalopram groups compared to placebo
QUALITY RATING:Fair
STUDY:Authors: Pallanti S, et al.141
Year: 2004
Country: Italy
FUNDING:Not reported
DESIGN:Study design: RCT
Setting: Single center
Sample size: 49
INTERVENTION:Citalopram and placeboCitalopram and Mirtazapine
Drug:citalopramcitalopram and mirtrazapine
Dose:20–80 mg/d and N/A20–80 mg/d and 15–30 mg/d
Duration:12 weeks12 weeks
Sample size:2821
INCLUSION:Diagnosis of OCD with co-morbid depression by structured clinical interview for DSM-IV Axis I and II disorders; OCD symptoms for 1 year; at least moderate severity on the CGI; SRI naive
EXCLUSION:Any of the following conditions: organic mental disorder, psychotic mental disorders, mental retardation, current depressive episode; substance or alcohol abuse; history of bipolar disorder; personality disorders; pregnant or nursing women
OTHER MEDICATIONS/INTERVENTIONS:Not reported
POPULATION CHARACTERISTICS:Groups similar at baseline: Yes
Mean age: citalopram/placebo 30.4; citalopram/mirtazapine 28.1
Gender (% female): citalopram/placebo 43%; citalopram/mirtazapine 43%
Ethnicity: Not reported
Other population characteristics: HAM-D total score: 8.7; CGI-S score: 5.4
OUTCOME ASSESSMENT:Primary Outcome Measures: Yale-Brown Obsessive Compulsive Scale (YBOCS)
Secondary Outcome Measures: HAM-D19; CGI-I, Arizona Sexual Experience Scale
Timing of assessments: At baseline and weekly thereafter.
RESULTS:
  • The citalopram/mirtazapine group showed an earlier response than the citalopram/placebo on reduction in mean YBOCS score; a significant between group difference was observed during weeks 2 through 6 (p < 0.05)
  • No significant between group difference in YBOCS score observed at endpoint.
  • No differences in CGI-I at endpoint
  • HAM-D not reported
ANALYSIS:ITT: Yes
Post randomization exclusions: No
ATTRITION:Loss to follow-up: 8.2% (4): Citalopram/placebo: 7.1% (2); citalopram/mirtazapine: 9.5% (2)
Withdrawals due to adverse events: 2% (1); citalopram/placebo: 3.6% (1); citalopram/mirtrazapine: 0%
Loss to follow-up differential high: No
ADVERSE EVENTS:
  • Mean Arizona Sexual Experience Scale score at endpoint was significantly worse in citalopram/placebo group than the citalopram/mirtrazapine (p < 0.01)
  • Significantly greater weight gain among citalopram/mirtrazapine group.
QUALITY RATING:Fair
STUDY:Authors: Piccinelli M, et. al.142
Year: 1995
Country: Italy
FUNDING:University of Verona
DESIGN:Study design: Meta-analysis
Number of patients: 1076
AIMS OF REVIEW:Efficacy of drug treatment in OCD; subgroup analysis: SSRIs vs. placebo
STUDIES INCLUDED IN META-ANALYSISPerse et al., 1987, Goodman et al., 1989a, Cottreaux et al., 1990, Jenike et al., 1990a, Rasmussen et al., (in press), Chouinard et al., 1990, Jenike et al., 1990b, Greist et al., (in press), Montgomery et al., 1993, Wood et al., 1993
TIME PERIOD COVERED:1975–1994
CHARACTERISTICS OF INCLUDED STUDIES:RCTs, double-blind placebo-controlled
CHARACTERISTICS OF INCLUDED POPULATIONS:DSM-III-R diagnosis of OCD; adult patients not refractory to standard treatments with OCD; no comorbid Tourette’s syndrome, phobia, depression or obsessive compulsive neurosis
CHARACTERISTICS OF INCLUDED INTERVENTIONS:13 trials of SSRI vs. placebo (fluoxetine, fluvoxamine, sertraline)
MAIN RESULTS:
  • Effect size calculated using Hedge’s g; a measure of the difference between the means of active treatment and placebo control; difference measures (Y-BOCS and NIMH-OC) abstracted from trials as the weighted mean g; positive values for Hedge’s g indicate greater improvement in the active treatment group, compared to placebo
  • Fluvoxamine vs. placebo:
    • Y-BOCS: 0.57 (95% CI: 0.37–0.77)
    • NIMH-OC: 0.29 (95% CI 0.07–0.51)
  • Fluoxetine vs. placebo:
    • Y-BOCS: 0.57 (95% CI: 0.33–0.81)
    • NIMH-OC: N/A
  • Sertraline vs. placebo:
    • Y-BOCS: 0.52 (95% CI: 0.27–0.77)
    • NIMH-OC: 0.55 (95% CI: 0.30–0.80)
  • Improvement rate over placebo (binominal effect size display, Rosenthal 1984):
    • Fluvoxamine: 28.2%
    • Fluoxetine: 28.5%
    • Sertraline: 21.6%
  • No statistically significant differences between study drugs
ADVERSE EVENTS:Not reported
COMPREHENSIVE LITERATURE SEARCH STRATEGY:Yes
STANDARD METHOD OF APPRAISAL OF STUDIES:Yes
QUALITY RATING:Good
STUDY:Authors: Soomro et al.143
Year: 2008
Country: Multinational
FUNDING:Cochrane
DESIGN:Study design: Systematic review and meta-analysis
Number of patients: 3097
AIMS OF REVIEW:To examine the efficacy and adverse effects of serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD) in adults
STUDIES INCLUDED IN REVIEWChouinard 1990; Dominguez 1991; Goodman 1989; Goodman 1996; Greist 1992b; Hollander 2002; Hollander 2003; Jenike 1990a; Jenike 1990b; Jenike 1997; Kamijima 2004; Kasper 1999; Kronig 1999; Montgomery 1993c; Nakajima 1996; Ushijima 1997; Zohar 1996
TIME PERIOD COVERED:Until December 2007
CHARACTERISTICS OF INCLUDED STUDIES:RCTs and quasi-RCTs
CHARACTERISTICS OF INCLUDED POPULATIONS:Adults with OCD
CHARACTERISTICS OF INTERVENTIONS:SSRIs compared with placebo
MAIN RESULTS:
  • Yale-Brown Obsessive Compulsive Scale (YBOCS) (WMD −3.21, 95% CI −3.84 to −2.57)
  • Clinical response RR 1.84, 95% CI 1.56 to 2.17
ADVERSE EVENTS:
  • Citalopram vs. placebo
    Overall AEs 71% vs, 58%, RR 1.22 (95% CI 1.02 to 1.45),
    Nausea 22% vs. 9% RR, 2.47 (95% CI 1.28 to 4.77). Headache 17% vs.167%, RR 1.05 (95% CI 0.63 to 1.76
    Insomnia 16% vs. 7%, RR 2.26 (95% CI 1.06 to 4.84) Sexual side effects RR 18.64, (95% CI of 1.15 to 302.80.
  • Fluoxetine vs. placebo
    Nausea, headache, insomnia and anxiety most common, Risk of these side effects for fluoxetine was similar to placebo, with the RR(REmodel) for these three side effects shown to be between 1.11 and 1.42, and 95% confidence intervals crossing 1.
  • Fluvoxamine vs. placebo
    Overall AEs 95% vs. 83%, RR 1.14 (95% CI 1.07 to 1.21)
    Asthenia 26 vs. 9 RR 2.83 (95% CI 1.74 to 4.60) Insomnia 34 vs. 18 RR 1.81 (95% CI 1.26 to 2.60)
    Nausea 31 vs. 12 RR 2.64 (95% CI 1.75 to 3.98) Somnolence 29 vs. 12 RR 2.46 (95% CI 1.59 to 3.79)
    Sexual side effects 14 vs. 3 RR 4.02 (95% CI 1.85 to 8.73).
  • Paroxetine vs. placebo
    Overall AEs 81 vs. 72 RR 1.14 (95% CI 0.91 to 1.42)
    Relative risk for asthenia and headache for paroxetine versus placebo was not statistically significant.
    Insomnia .23% vs. 14% RR1.71 (95% CI 1.15 to 2.53) Somnolence 27% vs. 11% RR 1.85 (95%CI 1.12 to 3.06),
    Nausea 3.96 (95%CI 1.82 to 8.61) Constipation 4.29 (95% CI 1.26 to 14.56).
  • Sertraline vs. placebo
    Overall AEs 87% vs, 68% RR 1.21 (95% CI 1.08 to 1.37)
    RR for nausea, dyspepsia,
    Differences in constipation, sedation, forgetfulness and headache for sertraline compared to placebo were not significant
    Insomnia 31 vs. 13 RR 2.23 (95% CI 1.09 to 4.56) Diarrhea 25 vs 10 RR 2.16 (95% CI 1.11 to 4.23),
    Sexual side effects 14 vs. 2 RR 5.74 (95% CI 0.68 to 48.31).
COMPREHENSIVE LITERATURE SEARCH STRATEGY:Yes - CCDANCTR-Studies and CCDANCTR-References
STANDARD METHOD OF APPRAISAL OF STUDIES:Yes
QUALITY RATING:Good
STUDY:Authors: Stein DJ, et al.144
Year: 1995
Country: South Africa and US
FUNDING:Not reported
DESIGN:Study design: Meta-analysis (SSRI vs. placebo only)
Number of patients: 516
AIMS OF REVIEW:Assess and integrate data from multiple clinical trials on drug treatment in OCD
STUDIES INCLUDED IN META-ANALYSISThis review addressed placebo-controlled trials, active control, and open label; we focus on SSRI vs. placebo.
Perse et al. 1987, Chouinard et al. 1990, Jenike et al. 1990, Montgomery et al. 1993
TIME PERIOD COVERED:1980–1993
CHARACTERISTICS OF INCLUDED STUDIES:RCTs; placebo-controlled SSRI trials detected by MedLine & PsychLit search; subjects rated with YBOCS or NIMH obsessive-compulsive global rating scale; trials at least six weeks in length; no specification on sample size
CHARACTERISTICS OF INCLUDED POPULATIONS:Diagnosis of OCD; adults; single medication without concomitant therapy
CHARACTERISTICS OF INCLUDED IINTERVENTIONS:Fluvoxamine (2 studies), fluoxetine (1 study), sertraline (2 studies)
MAIN RESULTS:
  • There were no differences in effect sizes between the SSRIs.
  • Effect size was calculated in comparison to placebo:
    • Fluvoxamine: 0.69 +− 0.47
    • Sertraline: 0.55
    • Fluoxetine: 0.51 +− 0.12
ADVERSE EVENTS:N/A
COMPREHENSIVE LITERATURE SEARCH STRATEGY:Yes
STANDARD METHOD OF APPRAISAL OF STUDIES:No
QUALITY RATING:Fair
STUDY:Authors: Stein et al.145
Year: 2007
Country: Multinational (7 countries)
FUNDING:H. Lundback A/S
DESIGN:Study design: RCT
Setting: Multicenter (58)
Sample size:
INTERVENTION:
Drug:PlaceboEscitalopram 10Escitalopram 20Paroxetine
Dose:NA10 mg/day20 mg/day40 mg/day
Duration:24 weeks24 weeks24 weeks24 weeks
Sample size:114113114117
INCLUSION:18–65 years, with a Y-BOCS of ≥20 at screening and baseline, □ an OCD duration ≥ 1 year, and symptoms that were stable for at least 6 months.
EXCLUSION:Within 6 months, MDD, panic disorder, GAD, social anxiety disorder, PTSD, eating disorder, body dysmorphic disorder, mental retardation or any pervasive developmental disorder, cognitive disorder (including dementia), schizotypal personality disorder, substance abuse disorder, motor/verbal tic disorder (including Tourette’s); a history of bipolar disorder, schizophrenia, or any psychotic disorder, patients with personality disorder that could interfere with the evaluation of the treatment for primary OCD; at risk of suicide (according to the investigator’s judgment), or had a score ≥ 5 on item 10 (suicidal thoughts) of the MADRS, or a MADRS total score ≥ 22, ECT, formal psychotherapy, or planned to initiate such therapy; a history of severe drug hypersensitivity, , treatment-refractory patients; pregnant, breast-feeding or not using adequate contraception. within 2 weeks prior to screening: monoamine oxidase inhibitors/reversible monoamine oxidase inhibitors, psychoactive herbal remedies, any other antidepressant or drug used for OCD treatment, dopamine antagonists, serotonergic agonists, or oral antipsychotics/mood stabilizers such as lithium; fluoxetine w/in 5 weeks, depot antipsychotics w/in 6 months, or ongoing prophylactic treatment with anticonvulsant or hypnotic drugs (except zolpidem, zopiclone, or zaleplon for insomnia, but not more than 3 days in a row and a maximum of 20 days in total during the study).
OTHER MEDICATIONS/INTERVENTIONS:See above
POPULATION CHARACTERISTICS:Groups similar at baseline: Yes
Mean age: 38
Gender (female %): Placebo 55.3 paroxetine40 53.8 escitalopram10 61.1 escitalopram20 57.9
Ethnicity: % Caucasian Placebo 94.7 paroxetine40 94.9 escitalopram10 93.8 escitalopram20 97.4
Other population characteristics:
OUTCOME ASSESSMENT:Primary Outcome Measures: mean change in Y-BOCS total score from baseline to week 12
Secondary Outcome Measures: mean change from baseline to week 24 in Y-BOCS total score, mean change from baseline to week 12 and to week 24 in Y-BOCS obsessional and compulsive subscores, change in the National Institute of Mental Health Obsessive–Compulsive Scale (NIMH-OCS)27 and Clinical Global Impressions – Severity (CGI-S) score from baseline to weeks 12 and 24, the CGI-I score, response and remission
Timing of assessments: Baseline weeks 4,8,12,16,20,24
RESULTS:
  • Y-BOCS total score at week 12 compared to placebo
    escitalopram 20 (mean difference of −3.21; 95% CI: −5.19 to −1.23, p < 0.01)
    paroxetine (mean difference of −2.47; 95% CI: −4.43 to −0.51, p < 0.05)
    escitalopram 10 (mean difference of −1.97; 95% CI: −3.97 to 0.02, p = 0.052).
  • The standardized effect sizes versus placebo at week 12 were ESC10 0.26 (95% CI: −0.003 to 0.53) esc20, 0.43 (95% CI: 0.16–0.69) for paroxetine 0.33 (95% CI: 0.07–0.66) for paroxetine.
  • No numbers were reported for 24 weeks, just figures.
ANALYSIS:ITT: Yes
Post randomization exclusions: 11
ATTRITION:Loss to follow-up: Overall 29% Placebo 32% paroxetine 32% escitalopram10 23% escitalopram20 27%
Withdrawals due to adverse events: NR
Withdrawals due to lack of efficacy: Placebo 18% paroxetine 8% escitalopram10 NR escitalopram20 6%
Loss to follow-up differential high: NO
ADVERSE EVENTS:Placebo vs. ESC 10 mg vs. ESC 20 mg vs. PAR 40 mg
Patients with AEs 73 (64.0%) vs. 80 (70.8%) vs. 86 (75.4%) vs. 94 (80.3%)
Nausea 14 (12.3%) vs. 22 (19.5%) vs. 31 (27.2%)* vs. 31 (26.5%)*
Headache 20 (17.5%) vs. 19 (16.8%) vs. 25 (21.9%) vs. 23 (19.7%)
Fatigue 6 (5.3%) vs. 13 (11.5%) vs. 20 (17.5%)* vs. 22 (18.8%)*
Somnolence 6 (5.3%) vs. 7 (6.2%) vs. 14 (12.3%) vs. 13 (11.1%)
Ejaculation delayed (men) 0 (0.0%) vs. 2 (4.5%) vs. 5 (10.4%)* vs. 5 (9.3%)
Libido decreased 1 (0.9%) vs. 3 (2.7%) vs. 8 (7.0%)* vs. 10 (8.5%)*
Hyperhidrosis 2 (1.8%) vs. 7 (6.2%) vs. 6 (5.3%) vs. 16 (13.7%)*
Influenza 7 (6.1%) vs. 6 (5.3%) vs. 1 (0.9%) vs. 1 (0.9%)*
  • P < 0.05
QUALITY RATING:Fair

From: Evidence Tables

Cover of Drug Class Review: Second-Generation Antidepressants
Drug Class Review: Second-Generation Antidepressants: Final Update 5 Report [Internet].
Gartlehner G, Hansen RA, Reichenpfader U, et al.
Portland (OR): Oregon Health & Science University; 2011 Mar.
Copyright © 2011 Oregon Health & Science University.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.