Paroxetine versus clomipramine in the treatment of obsessive-compulsive disorder. OCD Paroxetine Study Investigators. Double-blind parallel comparison of three dosages of sertraline and placebo in outpatients with obsessive-compulsive disorder. Adding quetiapine to SRI in treatment-resistant obsessive-compulsive disorder: a randomized controlled treatment study. Efficacy of fluvoxamine in obsessive-compulsive disorder. A double-blind comparison with placebo. Inositol versus placebo augmentation of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder: a double-blind cross-over study. A double-blind, placebo-controlled study of fluoxetine in patients with DSM-III-R obsessive-compulsive disorder. The Lilly European OCD Study Group. A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder. Fluoxetine in children and adolescents with OCD: a placebo-controlled trial. A multicenter investigation of fixed-dose fluoxetine in the treatment of obsessive-compulsive disorder. Cognitive and behavioral therapies alone versus in combination with fluvoxamine in the treatment of obsessive compulsive disorder. Placebo-controlled trial of fluoxetine and phenelzine for obsessive-compulsive disorder. Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial. A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder. Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder.
The aim was to assess the effect of a flexible dose of paroxetine, compared with clomipramine and placebo, in obsessive-compulsive disorder (OCD).
                In a multinational randomised study, 406 subjects with OCD of at least six months duration received double-blind medication for up to 12 weeks. Doses were adjusted according to therapeutic effect and side-effects. Primary efficacy measures were the Yale-Brown Obsessive-Compulsive Scale and the National Institute of Mental Health Obsessive-Compulsive Scale. Secondary efficacy measures were the Montgomery-Asberg Depression Rating Scale, Symptom Check-List (90), Clinical Global Impression, and Patients Global Evaluation.
                Paroxetine was significantly more effective than placebo, and of comparable efficacy to clomipramine. Paroxetine had significantly superior tolerability to clomipramine on three measures: CGI efficacy index, anticholinergic adverse events, and adverse events leading to withdrawal.
                Paroxetine is as effective as clomipramine in the treatment of OCD. The comparable efficacy and better tolerability of paroxetine suggest that it would be an appropriate treatment for OCD. Anecdotal evidence suggests patients with obsessive-compulsive disorder (OCD) are treated with selective serotonin uptake inhibitors at dosages significantly higher than those used with depressed patients. The current study examined the efficacy, safety, and optimal dosing strategy of sertraline in patients with OCD.
                Three hundred twenty-four nondepressed outpatients with OCD from 11 sites followed identical protocols using a double-blind parallel design. Following 1 week of single-blind placebo, patients were randomly assigned to 12 weeks of treatment with one of three fixed dosages of sertraline (50, 100, or 200 mg/d) or placebo.
                Sertraline patients exhibited significantly greater improvement (P < .05) at end point than placebo patients on all three main efficacy measures in the 50-mg/d and 200-mg/d groups and on one measure in the 100-mg/d group. The placebo response was larger in this population of subjects with OCD than in those previously studied. Adverse experiences were common in the sertraline and placebo groups and appeared to be dose-related in the sertraline-treated patients.
                Results support the safety and efficacy of daily dosages of 50, 100, and 200 mg of sertraline in the short-term treatment of patients with OCD. This study aimed to determine the efficacy and tolerability of adding quetiapine to a serotonin reuptake inhibitor in treatment-resistant obsessive-compulsive disorder (OCD). Twenty-one adult treatment-resistant OCD patients were randomized to 16 weeks of augmentation with either quetiapine (n = 11) or placebo (n = 10). Patients with significant comorbidities, including tic-spectrum disorders, were not included. The treatment was well tolerated, with only one premature dropout in each treatment-group. The primary analysis showed that individuals in the quetiapine-treated group showed a 14% mean improvement in baseline Yale-Brown Obsessive-Compulsive Scale scores at study endpoint compared with a 6% improvement in those treated with placebo, but this difference did not reach statistical significance (F<1). Three patients treated with quetiapine met criteria for clinical response, compared to one patient who was treated with placebo. Larger studies are needed to explore the efficacy of second generation antipsychotics, such as quetiapine, when used as adjunct treatment in resistant OCD. A six- to eight-week double-blind placebo-controlled trial of the potent and selective serotonin reuptake inhibitor fluvoxamine was conducted in 42 patients with primary obsessive-compulsive disorder (OCD). Approximately one half of the patients also had symptoms of major depression. Fluvoxamine was significantly better than placebo on all measures of obsessive-compulsive symptoms. Nine of 21 patients were responders ("much improved") with fluvoxamine compared with no responders with placebo, and fluvoxamine was effective in patients with OCD both with and without secondary depression. Response of OCD was not correlated with severity of baseline depression. These data lend partial support to the serotonin hypothesis of OCD. However, since a number of patients failed to respond to fluvoxamine, the role of other neurochemical systems in this disorder needs to be explored. Current serotonin reuptake inhibitor (SRI) treatments for obsessive-compulsive disorder (OCD) provide only partial benefit. A previous study suggested that inositol alone is efficacious in OCD. Ten DSM-IV OCD patients completed a study of 18 g inositol or placebo for 6 wk each in addition to ongoing SRI treatment in a double-blind randomized cross-over design. Weekly assessments included the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Hamilton Depression and Anxiety scales. No significant difference was found between the two treatment phases. We have studied the effect of three fixed daily doses of fluoxetine in patients with obsessive-compulsive disorder (OCD) diagnosed according to DSM-III-R. Two hundred and fourteen patients were evaluated in an 8-week double blind, placebo-controlled study. A statistically significantly greater number of fluoxetine-treated patients achieved the prospectively defined criteria for clinical response when compared to placebo treatment. There was a statistically significant overall difference in the PGI rating of symptom change (P = 0.045) and a marginally significant difference (P = 0.089) in the CGI severity rating between groups. Pairwise comparison against placebo showed a marginally statistically significantly greater improvement (P = 0.059) in Y-BOCS-Total score for patients receiving fluoxetine 60 mg daily, and a significantly higher response rate in patients receiving fluoxetine 40 mg or 60 mg daily (P < 0.05). One hundred and sixty one patients continued to a 16-week extension evaluation. There was no significant difference in the rate of reporting of any individual adverse event between placebo and fluoxetine, and the rate of discontinuation due to adverse events was low (< 6% in each study phase). This study supports the growing evidence for the safety and efficacy of fluoxetine in the treatment of OCD. One of the few combination approaches to the treatment of obsessive-compulsive disorder (OCD) with encouraging support is the addition of an antipsychotic to a serotonin reuptake inhibitor.
                The study consisted of a 6-week, placebo-controlled addition of olanzapine 5-10 mg (6.1 +/- 2.1 mg, mean +/- SD) to fluoxetine in OCD subjects who were partial or nonresponders to an 8-week, open-label fluoxetine trial (40 mg in 43 subjects, 20 mg in 1 subject).
                Both the fluoxetine-plus-olanzapine (n = 22) and fluoxetine-plus-placebo (n = 22) groups improved significantly over 6 weeks [F(3,113) = 11.64, p <.0001] according to Yale-Brown Obsessive Compulsive Scale scores with repeated-measures analysis of variance; however, the treatment x time interaction was not significant for olanzapine versus placebo addition to fluoxetine.
                These findings indicate no additional advantage of adding olanzapine for 6 weeks in OCD patients who have not had a satisfactory response to fluoxetine for 8 weeks, compared with extending the monotherapy trial. To examine the safety and efficacy of fluoxetine in child and adolescent obsessive-compulsive disorder (OCD).
                Between 1991 and 1998, 43 patients were randomly assigned to fluoxetine or placebo for 8 weeks. Dosing was fixed for the first 6 weeks (up to 60 mg/day) and then could be increased to 80 mg/day. Responders entered an 8-week maintenance phase. The primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impression-Improvement (CGI-I) scale. Analyses were done on the intent-to-treat sample.
                Fluoxetine patients (n = 21) had significantly lower CY-BOCS scores than placebo patients (n = 22) after 16 (but not 8) weeks. Fluoxetine responders (n = 11) had significantly lower CY-BOCS scores than placebo responders (n = 7) after an additional 8 weeks of treatment. After 16 weeks, 57% of fluoxetine (versus 27% of placebo) patients were much or very much improved on the CGI-I scale (p <.05). No patient terminated the study because of adverse medication effects.
                Fluoxetine was well tolerated and effective for the treatment of child and adolescent OCD, but fluoxetine's full effect took more than 8 weeks to develop. To determine the effectiveness of fluoxetine hydrochloride at fixed doses of 20 mg/d, 40 mg/d, and 60 mg/d in patients with obsessive-compulsive disorder (OCD) and to evaluate its safety.
                Fixed-dose fluoxetine hydrochloride (20 mg/d, 40 mg/d, 60 mg/d) was compared with placebo in two randomized, double-blind, parallel, 13-week trials of identical design in 355 outpatients with OCD aged 15 to 70 years (DSM-III-R criteria; 1 year's duration or longer; depression secondary if present).
                Fluoxetine (all doses) was significantly (P < or = .001) superior to placebo on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score (mean baseline-to-end-point decrease, 4.6, 5.5, and 6.5 vs 0.9, respectively, studies pooled) and other efficacy measures (P < or = .01). A trend suggesting greater efficacy at 60 mg/d was observed. Most patients (79.2%) completed the study. Eight adverse events were statistically significantly more frequent with fluoxetine and one, with placebo. For some events, incidence tended to increase with increasing dosage; however, few patients discontinued treatment for any single event.
                Fluoxetine was associated with a statistically significant reduction in OCD severity, including time engaged in obsessional and/or compulsive behaviors. Adverse events infrequently led to study discontinuation. The purpose of this treatment package design study was to investigate the differential efficacy of cognitive therapy or exposure in vivo with response prevention for obsessive compulsive disorder (OCD) versus the sequential combination with fluvoxamine. Patients with OCD (N = 117) were randomized to one of the following five conditions: a) cognitive therapy for weeks 1 to 16, b) exposure in vivo with response prevention for weeks 1 to 16, c) fluvoxamine for weeks 1 to 16 plus cognitive therapy in weeks 9 to 16, d) fluvoxamine for weeks 1 to 16 plus exposure in vivo with response prevention in weeks 9 to 16, or e) waiting list control condition for weeks 1 to 8 only. Assessments took place before treatment (pretest) and after 8 (midtest), and 16 weeks (posttest). In the first 8 weeks, six treatment sessions were delivered. During weeks 9 to 16, another 10 sessions were given. Thirty-one patients dropped out. Outcome was assessed by patient-, therapist- and assessor-ratings of the Anxiety Discomfort Scale, the Yale-Brown Obsessive Compulsive Scale, and the Padua Inventory-Revised. In contrast with the four treatments, after 8 weeks the waiting list control condition did not result in a significant decrease of symptoms. After 16 weeks of treatment, all four treatment packages were effective on these OCD ratings, but they did not differ among each other in effectiveness. In OCD, the sequential combination of fluvoxamine with cognitive therapy or exposure in vivo with response prevention is not superior to either cognitive therapy or exposure in vivo alone. It is now well documented that fluoxetine is a viable treatment option for patients with obsessive-compulsive disorder (OCD), and there is a small body of evidence indicating that monoamine oxidase inhibitors may be effective in at least a subset of patients. The authors conducted a 10-week placebo-controlled trial of these two agents in patients who met DSM-III-R criteria for OCD.
                Sixty-four subjects were randomly assigned to receive placebo, phenelzine (60 mg/day), or fluoxetine (80 mg/day). These doses were achieved by the end of week 3 of the active phase of the study. Outcomes were assessed with standardized instruments to measure OCD, mood, and anxiety.
                Fifty-four patients completed the study. There was a significant difference among the three treatments on one OCD scale, with fluoxetine-treated patients improving significantly more than those in the placebo or phenelzine group. A subgroup of OCD patients with symmetry obsessions did respond to phenelzine.
                This study provides no evidence to support the use of phenelzine in OCD except possibly for those patients with symmetry or other atypical obsessions. There was also no support for the hypothesis that patients with high levels of anxiety would respond preferentially to phenelzine. The empirical literature on treatment of obsessive-compulsive disorder (OCD) in children and adolescents supports the efficacy of short-term OCD-specific cognitive-behavior therapy (CBT) or medical management with selective serotonin reuptake inhibitors. However, little is known about their relative and combined efficacy.
                To evaluate the efficacy of CBT alone and medical management with the selective serotonin reuptake inhibitor sertraline alone, or CBT and sertraline combined, as initial treatment for children and adolescents with OCD.
                The Pediatric OCD Treatment Study, a balanced, masked randomized controlled trial conducted in 3 academic centers in the United States and enrolling a volunteer outpatient sample of 112 patients aged 7 through 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD and a Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score of 16 or higher. Patients were recruited between September 1997 and December 2002.
                Participants were randomly assigned to receive CBT alone, sertraline alone, combined CBT and sertraline, or pill placebo for 12 weeks.
                Change in CY-BOCS score over 12 weeks as rated by an independent evaluator masked to treatment status; rate of clinical remission defined as a CY-BOCS score less than or equal to 10.
                Ninety-seven of 112 patients (87%) completed the full 12 weeks of treatment. Intent-to-treat random regression analyses indicated a statistically significant advantage for CBT alone (P = .003), sertraline alone (P = .007), and combined treatment (P = .001) compared with placebo. Combined treatment also proved superior to CBT alone (P = .008) and to sertraline alone (P = .006), which did not differ from each other. Site differences emerged for CBT and sertraline but not for combined treatment, suggesting that combined treatment is less susceptible to setting-specific variations. The rate of clinical remission for combined treatment was 53.6% (95% confidence interval [CI], 36%-70%); for CBT alone, 39.3% (95% CI, 24%-58%); for sertraline alone, 21.4% (95% CI, 10%-40%); and for placebo, 3.6% (95% CI, 0%-19%). The remission rate for combined treatment did not differ from that for CBT alone (P = .42) but did differ from sertraline alone (P = .03) and from placebo (P<.001). CBT alone did not differ from sertraline alone (P = .24) but did differ from placebo (P = .002), whereas sertraline alone did not (P = .10). The 3 active treatments proved acceptable and well tolerated, with no evidence of treatment-emergent harm to self or to others.
                Children and adolescents with OCD should begin treatment with the combination of CBT plus a selective serotonin reuptake inhibitor or CBT alone. To date, only 1 controlled study has found a drug (haloperidol) to be efficacious in augmenting response in patients with obsessive-compulsive disorder (OCD) refractory to serotonin reuptake inhibitor (SRI) monotherapy; patients with comorbid chronic tic disorders showed a preferential response. This report describes the first controlled study of risperidone addition in patients with OCD refractory to treatment with SRI alone.
                Seventy adult patients with a primary DSM-IV diagnosis of OCD received 12 weeks of treatment with an SRI. Thirty-six patients were refractory to the SRI and were randomized in a double-blind manner to 6 weeks of risperidone (n = 20) or placebo (n = 16) addition. Behavioral ratings, including the Yale-Brown Obsessive Compulsive Scale, were obtained at baseline and throughout the trial. Placebo-treated patients subsequently received an identical open-label trial of risperidone addition.
                For study completers, 9 (50%) of 18 risperidone-treated patients were responders (mean daily dose, 2.2 +/-0.7 mg/d) compared with 0 of 15 in the placebo addition group (P<. 005). Seven (50%) of 14 patients who received open-label risperidone addition responded. Risperidone addition was superior to placebo in reducing OCD (P<.001), depressive (P<.001), and anxiety (P =.003) symptoms. There was no difference in response between OCD patients with and without comorbid diagnoses of chronic tic disorder or schizotypal personalty disorder. Other than mild, transient sedation, risperidone was well tolerated.
                These results suggest that OCD patients with and without comorbid chronic tic disorders or schizotypal personality disorder may respond to the addition of low-dose risperidone to ongoing SRI therapy. The safety and efficacy of sertraline versus placebo were examined in a group of nondepressed outpatients with obsessive-compulsive disorder (OCD). Patients with moderate-to-severe OCD were recruited at 10 sites. After a 1-week placebo lead-in, patients were treated in a double-blind fashion for 12 weeks with sertraline or placebo. Sertraline was administered at a starting dose of 50 mg/day, with flexible titration up to 200 mg/day. The efficacy measures were the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH), and the Clinical Global Impression Scale (CGI) Severity of Illness and Improvement subscales. One hundred sixty-seven patients were randomly assigned and received at least one dose of double-blind medication: 86 received sertraline and 81 received placebo. All efficacy measures showed significantly greater improvement in the sertraline group from the end of week 8 until the end of week 12. Significantly greater improvement (p < 0.05) in the sertraline group first became apparent by the end of week 3 on the Y-BOCS and the CGI Improvement scale, and by the end of weeks 6 and 8, respectively, on the NIMH and CGI Severity scale. Sertraline was well tolerated, without serious adverse effects. In conclusion, sertraline was safe and effective in the treatment of patients with OCD.
SSRIs are more effective than placebo for OCD, at least in the short-term, although there are differences between the adverse effects of individual SSRI drugs. The longer term efficacy and tolerability of different SSRI drugs for OCD has yet to be established.