title: Fluoxetine, but not Tricyclic Antidepressants, Potentiates the 5-Hydroxytryptophan-Mediated Increase in Plasma Cortisol and Prolactin Secretion in Subjects with Major Depression or with Obsessive Compulsive Disorder Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder. Sertraline in children and adolescents with obsessive-compulsive disorder: a multicenter randomized controlled trial. Fluoxetine treatment for obsessive-compulsive disorder in children and adolescents: a placebo-controlled clinical trial. A randomized controlled clinical trial of Citalopram versus Fluoxetine in children and adolescents with obsessive-compulsive disorder (OCD) Double-blind comparison of fluoxetine versus clomipramine in the treatment of obsessive compulsive disorder Placebo-controlled trial of fluoxetine and phenelzine for obsessive-compulsive disorder. A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder A pilot controlled study of fluoxetine for obsessive-compulsive symptoms in children with Tourette's syndrome. Delayed obsessive-compulsive disorder symptom exacerbation after a single dose of a serotonin antagonist in fluoxetine-treated but not untreated patients Double-blind study of adjuvant buspirone for fluoxetine-treated patients with obsessive-compulsive disorder. Double-blind, placebo-controlled, pilot trial of paliperidone augmentation in serotonin reuptake inhibitor-resistant obsessive-compulsive disorder. Paroxetine treatment in children and adolescents with obsessive-compulsive disorder: a randomized, multicenter, double-blind, placebo-controlled trial. Fluoxetine in children and adolescents with OCD: a placebo-controlled trial. Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial.
abstract: It has been suggested that the clinical efficacy of chronic treatment with selective serotonin reuptake inhibitors ( SSRIs ) such as fluoxetine and perhaps all antidepressants is due to their ability to enhance serotonergic activity . The effects of chronic treatment with fluoxetine or tricyclic antidepressants on the L-5-hydroxytryptophan ( 200 mg , L-5-HTP ; PO)–induced increases in plasma cortisol and prolactin ( PRL ) concentrations were studied in patients with major depression or obsessive compulsive disorder ( OCD ) . Administration of L-5-HTP increased plasma cortisol and PRL levels in medicated and unmedicated patients with major depression or OCD . The  L-5-HTP – induced cortisol and PRL responses were significantly higher in fluoxetine-treated than in tricyclic-treated or unmedicated major depressed patients . The latter two groups did not differ significantly in their cortisol or PRL responses to L-5-HTP . The L-5-HTP – induced increases in cortisol and PRL in fluoxetine-treated patients with major depression or OCD were not significantly different . The results suggest that fluoxetine , but not tricyclic antidepressants , potentiates 5-HT receptor – mediated stimulation of cortisol and PRL secretion in humans , consistent with available evidence that fluoxetine treatment , but not tricyclic antidepressants , increases central serotonergic activity in patients with MD or OCD by a presynaptic mechanism Rigorously design ed clinical trials have demonstrated the efficacy and safety of fluoxetine in adults with major depressive disorder and obsessive-compulsive disorder ( OCD ) but not in patients below 18 years old . This report describes a r and omized , double-blind , placebo-controlled , fixed-dose ( 20 mg qd ) trial of fluoxetine in 14 children and adolescents with OCD , ages 8 to 15 years old ; the study was 20 weeks long with crossover at 8 weeks . Obsessive-compulsive symptom severity was measured on the Children 's Yale-Brown Obsessive Compulsive Scale ( CY-BOCS ) and the Clinician 's Global Impression-Obsessive Compulsive Disorder scale ( CGI-OCD ) . The CY-BOCS total score decreased 44 % ( N = 7 , p = .003 ) after the initial 8 weeks of fluoxetine treatment , compared with a 27 % decrease ( N = 6 , p = .13 ) after placebo . During the initial 8 weeks , the magnitude of improvement for the fluoxetine group significantly exceeded that for the placebo group as measured by the CGI-OCD ( p = .01 ) but not by the CY-BOCS ( p = .17 ) . The most common drug side effects were generally well tolerated . The results suggest that fluoxetine is a generally safe and effective short-term treatment for children with OCD CONTEXT The serotonin reuptake inhibitors are the treatment of choice for patients with obsessive-compulsive disorder ; however , empirical support for this assertion has been weaker for children and adolescents than for adults . OBJECTIVE To evaluate the safety and efficacy of the selective serotonin reuptake inhibitor sertraline hydrochloride in children and adolescents with obsessive-compulsive disorder . DESIGN R and omized , double-blind , placebo-controlled trial . PATIENTS One hundred eighty-seven patients : 107 children aged 6 to 12 years and 80 adolescents aged 13 to 17 years r and omized to receive either sertraline ( 53 children , 39 adolescents ) or placebo ( 54 children , 41 adolescents ) . SETTING Twelve US academic and community clinics with experience conducting r and omized controlled trials . INTERVENTION Sertraline hydrochloride was titrated to a maximum of 200 mg/d during the first 4 weeks of double-blind therapy , after which patients continued to receive this dosage of medication for 8 more weeks . Control patients received placebo . MAIN OUTCOME MEASURES The Children 's Yale-Brown Obsessive Compulsive Scale ( CY-BOCS ) , the National Institute of Mental Health Global Obsessive Compulsive Scale ( NIMH GOCS ) , and the NIMH Clinical Global Impressions of Severity of Illness ( CGI-S ) and Improvement ( CGI-I ) rating scales . RESULTS In intent-to-treat analyses , patients treated with sertraline showed significantly greater improvement than did placebo-treated patients on the CY-BOCS ( adjusted mean , -6.8vs -3.4 , respectively ; P=.005 ) , the NIMH GOCS ( -2.2 vs -1.3 , respectively ; P=.02 ) , and the CGI-I ( 2.7 vs 3.3 , respectively ; P=.002 ) scales . Significant differences in efficacy between sertraline and placebo emerged at week 3 and persisted for the duration of the study . Based on CGI-I ratings at end point , 42 % of patients receiving sertraline and 26 % of patients receiving placebo were very much or much improved . Neither age nor sex predicted response to treatment . The incidence of insomnia , nausea , agitation , and tremor were significantly greater in patients receiving sertraline ; 12 ( 13 % ) of 92 sertraline-treated patients and 3 ( 3.2 % ) of 95 placebo-treated patients discontinued prematurely because of adverse medical events ( P=.02 ) . No clinical ly meaningful abnormalities were apparent on vital sign determinations , laboratory findings , or electrocardiographic measurements . CONCLUSION Sertraline appears to be a safe and effective short-term treatment for children and adolescents with obsessive-compulsive disorder OBJECTIVE This study assesses the efficacy and tolerability of fluoxetine in the acute treatment of child and adolescent obsessive-compulsive disorder ( OCD ) during a 13-week , double-blind , placebo-controlled study . METHOD Eligible patients aged 7 to 17 ( N = 103 ) were r and omized at a ratio of 2:1 to receive either fluoxetine or placebo . Dosing was initiated at 10 mg daily for 2 weeks , then increased to 20 mg daily . After 4 weeks of treatment , and again after 7 weeks of treatment , non-responders could have their dosage increased by 20 mg daily , for a maximum possible dosage of 60 mg daily . Primary measure of efficacy was improvement in OCD symptoms as measured by the Children 's Yale-Brown Obsessive Compulsive Scale ( CY-BOCS ) . All analyses were intent-to-treat . RESULTS Fluoxetine was associated with significantly greater improvement in OCD as assessed by the CY-BOCS ( p = .026 ) and other measures than was placebo . Fluoxetine was well tolerated and had a rate of discontinuation for adverse events similar to that of placebo ( p = 1.00 ) . CONCLUSIONS Fluoxetine 20 to 60 mg daily was effective and well tolerated for treatment of OCD in this pediatric population ObjectiveS everal controlled trials have demonstrated the efficacy and safety of Fluoxetine in children and adolescents with Obsessive-Compulsive Disorder ( OCD ) , but there is no controlled study on the effectiveness of Citalopram in this group . This report describes the use of Citalopram in comparison with Fluoxetine in childhood-onset OCD . Method This study is a r and omized , double blind , fixed-does ( 20 mg ) trial of Fluoxetine versus Citalopram in 29 children and adolescents ( 17 boys and 12 girls ) with OCD , aged 7–18 years ( mean 13.8 and SD 3.05 ) . The length of study was 6 weeks . Obsessive-Compulsive symptom severity was measured by Yale – Brown Obsessive-Compulsive Scale ( CY-BOCS ) and Clinician ’s Global Impression Scale ( CGI ) . DICA ( Diagnostic Interview of Children and Adolescents ) was used to diagnose the psychiatric disorders . Results Each group showed significant improvement over the baseline as measured by the CY-BOCS ( p < 0.01 ) but not by CGI ( p = NS ) . The Comparison between two groups showed no significant differences in efficacy and safety of the drugs . Most common adverse effects were headache for Citalopram and tremor for Fluoxetine . Conclusion The results suggest that Citalopram is as safe and effective as Fluoxetine for children and adolescents with OCD . Further studies are needed to replicate our findings There is evidence of the clinical efficacy and safety of clomipramine and the newer selective serotonin reuptake inhibitors ( SSRIs ) for the treatment of obsessive-compulsive disorder ( OCD ) . In the present study , we have compared the efficacy and safety of 40 mg/day of fluoxetine and 150 mg/day of clomipramine in patients with OCD , diagnosed according to DSM-IIIR . A total of 55 patients entered this 8-week , double-blind controlled study . Efficacy for both drugs was comparable . The primary efficacy criterion , the Y-BOCS Total score , did not show any significant differences between treatment arms . Response rate was higher with clomipramine , using a 25 % decrease in Y-BOCS Total score as response threshold , but there were no significant differences between treatment arms using a 35 % threshold . Overall safety and tolerability were good for both drugs , being slightly better for fluoxetine OBJECTIVE 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 . METHOD Sixty-four subjects were r and omly 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 st and ardized instruments to measure OCD , mood , and anxiety . RESULTS 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 . CONCLUSIONS 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 BACKGROUND 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 . METHODS 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 ) . RESULTS 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 . CONCLUSIONS 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 We carried out a double-blind , r and omized , parallel-groups clinical trial of fluoxetine ( 20 - 40 mg/day ) and placebo in 11 children with Tourette 's syndrome ( TS ) and associated obsessive-compulsive symptoms ( OCS ) . The treatment period lasted 4 months . No significant differences between treatment groups were observed for measures of OCS .  Fluoxetine therapy , however , was associated with a trend toward some improvement in tic severity , attentional abilities , and social functioning . Given these observations and the limitations of this pilot study , which include selection biases , small sample size , and significant placebo effects , the efficacy of fluoxetine in children with TS deserves further larger-scale investigation Abstract Enhanced serotonergic transmission may underlie therapeutic effects of serotonin reuptake inhibitors in obsessive-compulsive disorder . However , such treatment may decrease serotonin receptor responsivity . We investigated whether the serotonin antagonist metergoline would exacerbate or further improve systems in fluoxetine-responsive patients . Pilot results suggested open metergoline produced delayed symptom worsening in fluoxetine-treated patients . Fourteen patients continuing fluoxetine received metergoline and placebo ( double-blind , r and omized ) . Symptom ratings continued for 1 week afterwards . Ten unmedicated patients underwent the same procedures . Symptoms improved 4 h after both metergoline and placebo . The day after metergoline but not placebo , fluoxetine-treated patients had significantly increased anxiety , obsessions and compulsions , abating over several days . Depression was unchanged . Metergoline had no similar delayed effects in unmedicated patients .  Metergoline levels were higher in fluoxetine-treated patients . These results , consistent with less conclusive earlier findings , suggest that prolonged changes in brain serotonin function underlie symptom re-emergence following administration of metergoline to fluoxetine-treated patients with obsessive-compulsive disorder In a double-blind , crossover study , 13 fluoxetine-treated patients with obsessive-compulsive disorder were given adjuvant buspirone and placebo for 4 weeks each . There were no significant differences between buspirone and placebo in obsessive-compulsive , depressive , or anxiety symptoms OBJECTIVE This pilot study explored the efficacy and tolerability of paliperidone augmentation of serotonin reuptake inhibitors ( SRIs ) in adults with treatment-resistant obsessive-compulsive disorder ( OCD ) . METHOD Thirty-four patients aged 24 - 67 years ( mean = 43.7 years , SD = 11.4 ) who met DSM-IV criteria for OCD and remained symptomatic following 2 or more past adequate SRI trials ( including their current medication ) were enrolled from May 2008 to March 2012 . Participants were treated for 8 weeks in a double-blind study with either paliperidone ( up to 9 mg/d ) or matching placebo in addition to their SRI . Blinded raters conducted outcome assessment s. The primary outcome , obsessive-compulsive symptom severity , was assessed using the Yale-Brown Obsessive Compulsive Scale ( YBOCS ) . Secondary outcomes included the Clinical Global Impressions-Severity of Illness and -Improvement scales . RESULTS Paliperidone administration result ed in significant baseline-to-posttreatment reductions in obsessive-compulsive symptoms as measured by the YBOCS ( P < .01 , d = 0.66 ) , although placebo administration also result ed in medium-sized , trend-level significant YBOCS changes ( P = .05 , d = 0.53 ) . In exploratory analyses examining between-group differences , tests for paliperidone superiority relative to placebo were not significant ( P = .14 , d = 0.34 ) ; however , a numerical trend toward significant between-group differences was found , with a reduction of 7.98 points on the YBOCS for the paliperidone group compared to a reduction of 4.02 points for the placebo group . Paliperidone was generally well tolerated and not associated with significant weight gain ( mean [ SD ] weight : paliperidone , pretreatment 84.70 [ 27.08 ] kg , posttreatment 84.84 [ 18.99 ] kg ; vs placebo , pretreatment 77.50 [ 25.33 ] kg , posttreatment 77.43 [ 19.90 ] kg ; P = .21 ) . CONCLUSIONS These results suggest that paliperidone augmentation is well tolerated and has potential efficacy in the short-term treatment of some patients with SRI-resistant OCD . Well-powered , r and omized , controlled studies are necessary to more definitively address the efficacy of this treatment strategy . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00632229 OBJECTIVE To assess the efficacy and safety of paroxetine for the treatment of pediatric obsessive-compulsive disorder . METHOD Children ( 7 - 11 years of age ) and adolescents ( 12 - 17 years of age ) meeting DSM-IV criteria for obsessive-compulsive disorder were r and omized to  paroxetine  ( 10 - 50 mg/day ) or placebo for 10 weeks . The primary efficacy measure was change from baseline in the Children 's Yale-Brown Obsessive-Compulsive Scale ( CY-BOCS ) total score at week 10 last observation carried forward end point . Safety was assessed primarily through adverse event monitoring . RESULTS A total of 207 patients were r and omized to treatment . Of these , 203 were included in the intention-to-treat population . Adjusted mean changes from baseline at week 10 observation carried forward end point in CY-BOCS total score for patients receiving paroxetine and placebo were -8.78 ( SE=0.82 ) and -5.34 points ( SE=0.77 ) , respectively . The adjusted mean difference , -3.45 in favor of paroxetine , was statistically significant ( 95 % confidence interval=-5.60 to -1.29 , p=.002 ) . Adverse events were generally mild to moderate in intensity . A total of 10.2 % ( 10/98 ) of patients in the paroxetine group and 2.9 % ( 3 of 105 ) in the placebo group discontinued treatment because of adverse events . CONCLUSIONS Paroxetine is an effective and generally well-tolerated treatment for obsessive-compulsive disorder in children and adolescents OBJECTIVE To examine the safety and efficacy of fluoxetine in child and adolescent obsessive-compulsive disorder ( OCD ) . METHOD Between 1991 and 1998 , 43 patients were r and omly 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 . RESULTS 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 . CONCLUSION 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 OBJECTIVE To determine the safety and efficacy of fluvoxamine for the treatment of children and adolescents with obsessive-compulsive disorder ( OCD ) with a double-blind , placebo-controlled , multicenter study . METHOD Subjects , aged 8 to 17 years , meeting DSM-III-R criteria for OCD were recruited from July 1991 to August 1994 . After a 7- to 14-day single-blind , placebo washout/screening period , subjects were r and omly assigned to fluvoxamine 50 to 200 mg/day or placebo for 10 weeks . Subjects who had not responded after 6 weeks could discontinue the double-blind phase of the study and enter a long-term , open-label trial of fluvoxamine . Analyses used an intent-to-treat sample with a last-observation-carried-forward method . RESULTS Mean Children 's Yale-Brown Obsessive Compulsive Scale ( CY-BOCS ) scores with fluvoxamine were significantly ( p < .05 ) different from those with placebo at weeks 1 , 2 , 3 , 4 , 6 , and 10 . Significant ( p < .05 ) differences between fluvoxamine and placebo were observed for all secondary outcome measures at all visits . Based on a 25 % reduction of CY-BOCS scores , 42 % of subjects taking fluvoxamine were responders compared with 26 % taking placebo . Forty-six ( 19 fluvoxamine , 27 placebo ) of 120 r and omized subjects discontinued early . Adverse events with a placebo-adjusted rate greater than 10 % were insomnia and asthenia . CONCLUSIONS Fluvoxamine has a rapid onset of action and is well tolerated and efficacious for the short-term treatment of pediatric OCD
target: Conclusions and implication s of key findings : Fluoxetine is associated with a significantly greater reduction in OCD severity , as measured by the CY-BOCS , NIMH-OC and CGI-S , in children and adolescents .
  Additionally , it is well tolerated in children and adolescents .
  The acceptability is comparable to that of the placebo-treated group .
background: Background : Obsessive-compulsive disorder ( OCD ) is a common psychiatric illness in children and adolescents .
  Previous evidence suggests that fluoxetine is effective in the treatment of OCD in children and adolescents .
  However , those studies had small sample sizes .
  As a result , a systematic review , which is a more powerful method to calculate the true effect size , can be applied to examine the efficacy , acceptability and tolerability of fluoxetine in the treatment of OCD in children and adolescents .
  Objectives : The aims of this study were to review the efficacy , acceptability and tolerability of fluoxetine in the treatment of OCD in children and adolescents .