Quetiapine augmentation of serotonin reuptake inhibitors in obsessive-compulsive disorder Quetiapine addition to serotonin reuptake inhibitor treatment in patients with treatment-refractory obsessive-compulsive disorder: an open-label study. Double-blind, placebo-controlled, pilot trial of paliperidone augmentation in serotonin reuptake inhibitor-resistant obsessive-compulsive disorder. A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder. Quetiapine Addition to Serotonin Reuptake Inhibitors in Patients With Severe Obsessive-Compulsive Disorder: A Double-Blind, Randomized, Placebo-Controlled Study Risperidone and haloperidol augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder: a crossover study. Amisulpiride augmentation in treatment resistant obsessive-compulsive disorder: an open trial. Quetiapine augmentation in patients with treatment resistant obsessive–compulsive disorder: a single-blind, placebo-controlled study Augmentation strategy with olanzapine in resistant obsessive compulsive disorder: an Italian long-term open-label study A double-blind, randomized, placebo-controlled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors. Olanzapine augmentation of paroxetine-refractory obsessive-compulsive disorder Risperidone augmentation in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. Reactivity of serotonin in whole blood: relationship with drug response in obsessive-compulsive disorder Predictors of response to pharmacotherapy with citalopram in obsessive-compulsive disorder Augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder using adjunctive olanzapine: a placebo-controlled trial. Adding quetiapine to SRI in treatment-resistant obsessive–compulsive disorder: a randomized controlled treatment study Six-month follow-up of a randomized controlled trial augmenting serotonin reuptake inhibitor treatment with exposure and ritual prevention for obsessive-compulsive disorder. Olanzapine augmentation for treatment-resistant obsessive-compulsive disorder. Low-dose risperidone augmentation of fluvoxamine treatment in obsessive-compulsive disorder: a double-blind, placebo-controlled study The Advantages of Choosing Antiobsessive Therapy According to Decision-Making Functioning A long-term trial of the effectiveness and safety of atypical antipsychotic agents in augmenting SSRI-refractory obsessive-compulsive disorder. N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial. Cognitive behavior therapy augmentation of pharmacotherapy in pediatric obsessive-compulsive disorder: the Pediatric OCD Treatment Study II (POTS II) randomized controlled trial.
The augmentation of serotonin reuptake inhibitors ( SRIs ) with atypical antipsychotics for the management of  treatment-resistant obsessive-compulsive disorder ( OCD ) is gaining increasing acceptance . Quetiapine is a novel antipsychotic which is well tolerated , and which may therefore be particularly useful in this context . Charts of all patients treated in our OCD clinic with the combination of an SRI and quetiapine  were review ed . Demographic details and clinical symptoms on the Yale-Brown Obsessive-Compulsive Scale and the Clinical Global Impressions Scale ( CGI ) were tabulated before and after augmentation . Eight OCD patients who had proven resistance to treatment with SRIs  had received quetiapine augmentation . Four of these eight patients were responders ( CGI of 1 or 2 ) within 4 weeks . In the treatment-responders , the medication was well tolerated . Although limited by the retrospective design and lack of controls , these data are consistent with the growing literature suggesting that approximately one-half of OCD patients resistant to treatment with SRIs  may respond to augmentation with an atypical antipsychotic . Quetiapine , a relatively well tolerated agent , deserves further controlled study in this context OBJECTIVE Although patients with obsessive-compulsive disorder ( OCD ) benefit from treatment with serotonin reuptake inhibitors ( SRIs ) , it is estimated that 40 % to 60 % of the patients remain unimproved . The objective of this study was to examine whether addition of the atypical antipsychotic quetiapine to SRIs is useful for patients with OCD who do not respond to SRI monotherapy . METHOD Ten patients with OCD ( DSM-IV criteria ) who had not responded to at least 3 previous treatments with an SRI at maximum dose and duration were assigned to receive quetiapine in addition to an SRI for 8 weeks . Treatment response was assessed using the Yale-Brown Obessive-Compulsive Scale ( YBOCS ) . RESULTS Seven of 10 patients responded to the quetiapine addition . The mean + /- SD baseline YBOCS score of 31.4 + /- 7.8 dropped to a mean of 20.8 + /- 8.4 at endpoint with a mean reduction of 35.4 % . CONCLUSION This is the first study to show that treatment-refractory OCD patients may benefit from addition of quetiapine to ongoing SRI therapy 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 BACKGROUND 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 . METHODS 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 r and omized 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 . RESULTS 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 . CONCLUSION 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 Objective : Although many patients with obsessive-compulsive disorder ( OCD ) benefit from treatment with serotonin reuptake inhibitors ( SRIs ) , it is estimated that 40 % to 60 % of them do not respond . The objective of the present study was to evaluate the efficacy of quetiapine added to baseline treatment with SRIs for the treatment of OCD in severely ill adult subjects . Method : Forty patients ( 21 men , 19 women ) with primary OCD according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria participated in a 12-week , double-blind , placebo-controlled trial . They were r and omly assigned to dosages of quetiapine titrated up to 400 mg/d ( n = 20 ) or to placebo ( n = 20 ) in addition to their SRI treatment . During the continuation phase ( weeks 6 - 12 ) , subjects received different dosages between 400 and 600 mg/d depending on clinical response . At entry , all patients were unresponsive to at least 1 course of at least 12 weeks of treatment with SRIs at defined doses . The total Yale-Brown Obsessive-Compulsive Scale score was the primary efficacy parameter . Results : Intention-to-treat , last-observation-carried-forward analysis demonstrated a mean ± SD decrease in Yale-Brown Obsessive-Compulsive Scale score of 5.2 ± 5.4 in the quetiapine group and 3.9 ± 4.9 in the placebo group . The analysis of treatment effects between the 2 groups showed no significant difference . There were no significant group differences in any of the other self-rating scales or clinician-administered rating scales . Conclusions : In this study , augmentation of SRI treatment with quetiapine in severe OCD had no additional effect BACKGROUND Although serotonin reuptake inhibitors ( SRIs ) are the first-line treatment for obsessive-compulsive disorder ( OCD ) , approximately half of patients with OCD do not respond adequately to SRI monotherapy . Patients with predominant obsessions are common in OCD and are often difficult to treat , necessitating adjunctive treatment . METHOD This was a 9-week , double-blind , placebo-controlled , crossover study comparing the benefits of 2-week adjunctive treatments with risperidone , haloperidol , and placebo in patients with OCD ( DSM-IV criteria ) who continued to have severe symptoms despite taking a stable dose of an SRI . Eligible patients must have been receiving a therapeutic dose of an SRI for at least 12 weeks and at the screening visit had a score > or = 10 on items 1 - 5 ( obsession ) and a total score > or = 16 on the Yale-Brown Obsessive Compulsive Scale ( YBOCS ) . Data were collected from January 1999 through April 2002 . RESULTS Sixteen patients were enrolled and 12 completed the study . On the YBOCS , both risperidone and haloperidol significantly reduced obsession ( p < .05 ) when compared with placebo . There was a tendency that haloperidol , and to a lesser degree risperidone , also reduced the compulsion and the total YBOCS scores . These results were accompanied by a reduction in the Hopkins Symptom Checklist 90-revised ( SCL-90R ) anxiety scale score . According to the 17-item Hamilton Rating Scale for Depression , the SCL-90R depression scale , and the Profile of Mood States , risperidone , but not halo-peridol , also improved depressed mood . Neither risperidone nor haloperidol changed neurocogni-tive function during the 2-week treatment . All 12 patients completed the 2-week risperidone treatment , but 5 of the 12 terminated haloperidol treatment early owing to intolerable side effects . CONCLUSION Adjunctive risperidone improved obsessions and depressed mood and was well tolerated in patients with SRI-refractory OCD Despite the effectiveness of clomipramine and selective serotonin reuptake inhibitors ( SSRIs ) in the treatment of obsessive-compulsive disorder ( OCD ) , 40 % to 60 % of patients who receive an adequate treatment with these agents have significant persisting symptoms . Newer atypical antipsychotic drugs showed efficacy as augmenting agents in patients with OCD resistant to serotonin reuptake inhibitors ( SRIs ) . The objective of this study was to evaluate the efficacy and safety of amisulpiride augmentation in treatment resistant OCD . A total of 20 patients diagnosed with OCD according to DSM-IV criteria and having a history of resistance to treatment with SRIs were included in the study .  Amisulpiride 200 mg/day was added to ongoing SRI treatment and titrated up to 600 mg/day in flexible doses . The mean amisulpiride dose was 325 + /- 106 mg/day . The patients were assessed with the Yale-Brown obsessive-compulsive scale ( Y-BOCS ) at baseline and at week 12 of amisulpiride treatment . Side effects were monitored by the UKU side effect rating scale . The reduction in Y-BOCS scores between the baseline ( 26.7 + /- 6.3 ) and the end of the treatment ( 12.5 + /- 2.8 ) was statistically significant ( p=0.0001 ) . The most commonly observed side effects included weight gain ( 14 patients , 70 % ) , mild sedation ( 13 patients , 65 % ) and asthenia ( 7 patients , 35 % ) . This study has several limitations and , hence , the results are preliminary and require confirmation in a r and omized controlled trial . In conclusion , this study suggests that amisulpiride may be a promising option as an augmentation strategy in treatment resistant OCD Recently , atypical antipsychotics have been used for the management of the patients with refractory obsessive – compulsive disorder ( OCD ) . The aim of the present study was to evaluate the results of quetiapine augmentation to a serotonin reuptake inhibitor ( SRI ) in the patients with refractory OCD . Fifty-two patients with OCD according to DSM-IV entered 3 months of an open-label phase treatment with a SRI with or without concomitant adjunctive treatment regimen . Of them , 27 patients were refractory OCD . These patients were r and omly divided into two groups , SRI plus quetiapine and SRI plus placebo , for an 8-week single-blind phase . The course of OCD was evaluated by Yale – Brown Obsession – Compulsion ( Y-BOCS ) and Clinical Global Impression – Severity of Illness and Improvement ( CGI-SI and I ) Scales every other week for 8 weeks . Of the 14 patients in group I , nine ( 64.4 % ) showed significant improvement with 60 % or greater improvement on the Y-BOCS and one ( 7.1 % ) partial improvement with 30 % or greater improvement on the Y-BOCS , whereas no improvement was observed in group II . The addition of quetiapine to ongoing SRI therapy has been found to be effective and well-tolerated approach in patients with refractory OCD The present study reports the results of an open-label trial on the use of the combination of olanzapine ( an atypical antipsychotic ) serotonin reuptake inhibitors ( SRIs ) in 26 resistant out patients affected by resistant obsessive-compulsive disorder ( OCD ) . All patients had been suffering from OCD , according to DSM IV criteria , for at least 2 years and had different comorbid disorders ; they had been treated with an  SRI  at adequate dosages for at least 6 months , or had tried different augmentation strategies with no or poor response . As a result , olanzapine was added and continued for 1 year . After 12 weeks of this regimen , most of the patients ( 17 ) had shown a reduction in OC symptoms , as assessed by a decrease in the Yale-Brown Obsessive Compulsive Scale total score , which continued throughout subsequent months . Only mild side-effects were recorded and no patient halted the treatment . The addition of olanzapine would appear to be a useful short- and long-term strategy for augmenting SRI effectiveness in resistant OCD patients , especially in those presenting comorbidity with bipolar disorders BACKGROUND Although serotonin reuptake inhibitors ( SRIs ) are the most effective pharmacologic treatment currently available for patients with obsessive-compulsive disorder ( OCD ) , 40 % to 60 % of patients do not respond to this treatment . This study was conducted to evaluate the efficacy and tolerability of quetiapine in addition to an SRI for treatment-refractory patients with OCD . METHOD Forty patients ( 10 men/30 women , mean + /- SD age = 35.2 + /- 12.1 years ; range , 18 - 60 years ) with primary OCD according to DSM-IV criteria who were recruited between February 2001 and December 2002 were r and omly assigned in an 8-week , double-blind , placebo-controlled trial to receive dosages titrated upward to 300 mg/day of quetiapine ( N = 20 ) or placebo ( N = 20 ) in addition to their SRI treatment . At entry , all patients were unresponsive to courses of treatment with at least 2 different  SRIs  at a maximum tolerated dose for 8 weeks . During the study , primary efficacy was assessed according to change from baseline on the Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) . A responder was defined as having a final Clinical Global Impressions-Improvement scale rating of " very much improved " or " much improved " and a decrease of > or = 35 % in Y-BOCS score . RESULTS An intent-to-treat , last-observation-carried-forward analysis demonstrated a mean + /- SD decrease in Y-BOCS score of 9.0 + /- 7.0 ( 31 % ) in the quetiapine group and 1.8 + /- 3.4 ( 7 % ) in the placebo group ( F=16.99 , df=1,38 ; p < .001 ) . Eight ( 40 % ) of 20 patients in the quetiapine group and 2 ( 10 % ) of 20 patients in the placebo group were responders ( chi2=4.8 , df=1 , p=.028 ) . The most common side effects in the quetiapine group were somnolence , dry mouth , weight gain , and dizziness . CONCLUSION The results of this study show that quetiapine in addition to an SRI is beneficial for patients with OCD who do not respond to SRI treatment alone The aim of the present study was to investigate the effect of adjunctive olanzapine in patients with obsessive-compulsive disorder ( OCD ) refractory to paroxetine . Twenty-one patients unresponsive to treatment with paroxetine , administered for at least 12 weeks at the dose of 60 mg/day , participated to a 12-week open-label , add-on trial with olanzapine ( 10 mg/day ) . The psychopathological state was evaluated by the Yale-Brown Obsessive-Compulsive Scale ( Y-BOCS ) and by Clinical Global Impression ( CGI ) . Three patients did not complete the 12-week adjunctive treatment with olanzapine . In the 18 completers , the mean Y-BOCS score decreased significantly from 27.1+/-4.0 at baseline to 20.1+/-3.9 at final evaluation ( P<.001 ) . Seven patients ( 38.9 % ) were rated as responders at final evaluation . Steady-state plasma concentrations of paroxetine  were not modified during olanzapine coadministration . The drug combination was generally well tolerated and initial sedation and weight gain were the most frequent unwanted effects . Our findings confirm the results of previous studies and indicate that the addition of olanzapine to ongoing treatment with serotonin reuptake inhibitors ( SRI ) may be beneficial in some patients unresponsive to SRI monotherapy This double-blind , placebo-controlled trial was performed to determine the efficacy and tolerability of 8 wk of risperidone augmentation of serotonin reuptake inhibitor ( SRI ) treatment in adult subjects with treatment-resistant obsessive-compulsive disorder ( OCD ) ( failure of at least two SRI trials ) . Sixteen adult treatment-resistant OCD patients were r and omly assigned to augmentation with 8 wk of either risperidone ( n=10 ) ( 0.5 - 3.0 mg/d ) or placebo ( n=6 ) following at least 12 wk of SRI treatment . Four patients on risperidone ( 40 % ) and none ( 0 % ) on placebo were responders with both a Clinical Global Impression - Improvement ( CGI-I ) score of 1 or 2 and a Yale-Brown Obsessive-Compulsive Scale ( Y-BOCS ) decrease > /=25 % . Risperidone was generally well tolerated : there were 3 dropouts , 1 on risperidone and 2 on placebo . Better Y-BOCS insight score at baseline significantly correlated with a greater CGI-I score at endpoint on risperidone augmentation . Risperidone may be an effective and well-tolerated augmentation strategy in treatment-resistant OCD subjects , but larger sample size studies are required to demonstrate this BACKGROUND Obsessive-compulsive disorder responds almost only to potent serotonin reuptake inhibitors . Previous studies have suggested a relation between serotonergic function and clinical outcome in serotonin reuptake inhibitor treatment of obsessive-compulsive disorder . METHODS In a r and omized , double-blind trial , comparing clomipramine , paroxetine , and a placebo in obsessive-compulsive disorder ,  serotonin levels in whole blood ( WB-5-HT ) were measured at baseline , after 1 week , and after 4 weeks of treatment and related to clinical outcome in 36 patients . RESULTS In patients treated with serotonin reuptake inhibitors  there was a pronounced decrease of WB-5-HT , variable after 1 week and uniformly maximal after 4 weeks . The decrease of WB-5-HT after 1 week of serotonin reuptake inhibitor treatment correlated negatively with clinical outcome after 12 weeks ( r = -.61 , p = .0006 ) ; hence , patients with slower WB-5-HT reactivity eventually responded better to treatment . Baseline WB-5-HT , but not WB-5-HT reactivity , was related to season . Depression , autistic traits , and previous serotonin reuptake inhibitor treatment predicted nonresponse . CONCLUSIONS A fast decrease of WB-5-HT was associated with poor clinical outcome . This may be related to faster serotonin efflux from platelets , which has previously been linked to autism . Further studies are necessary to identify the underlying mechanism and discern whether serotonin reuptake inhibitor-induced WB-5-HT decrease is clinical ly useful Although serotonin reuptake inhibitors ( SRIs ) are the medications of choice in the treatment of obsessive-compulsive disorder ( OCD ) , only 50 - 60 % of patients respond to a single trial of any of these agents . Improved knowledge of the predictors of response to treatment may have important clinical implication s. Data from a large r and omized placebo-controlled trial of citalopram in OCD was analysed using logistic regression to determine predictors of response . Demographic ( age , sex ) , clinical ( OCD severity and duration , depression severity , prior treatment ) and trial variables  ( citalopram dose , treatment duration ) were included . Subjects with longer duration of OCD , more severe OCD symptoms or previous selective SRI use were less likely to be responders in the citalopram trial . In contrast , subjects who received adequate medication doses for sufficient periods of time in the citalopram trial were more likely to be responders . Despite greater awareness of OCD in recent years , there is evidence that the disorder continues to be underdiagnosed and undertreated . The data here emphasize the crucial importance of early diagnosis and treatment of OCD , and of pharmacotherapy with appropriate dose and duration BACKGROUND The purpose of this study was to explore the efficacy of adding an atypical antipsychotic , olanzapine , to a serotonin reuptake inhibitor ( SRI ) in treatment-refractory obsessive-compulsive disorder ( OCD ) . METHOD Twenty-six patients aged between 18 and 65 ( mean = 41.2 , SD = 11.9 ) years meeting DSM-IV criteria for OCD , who had not responded to SRIs , were treated for 6 weeks in a double-blind , placebo-controlled augmentation study with either olanzapine ( up to 20 mg/day ) or placebo . Severity of illness was assessed biweekly by the Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) . Analysis of covariance with baseline Y-BOCS score included as a covariate was used to compare improvement in Y-BOCS scores in the 2 groups . Response was defined as a 25 % or greater improvement in Y-BOCS score . Data were collected between April 2001 and May 2003 . RESULTS Outcome was assessed for all patients using the last observation carried forward . Subjects in the olanzapine group had a mean decrease of 4.2 ( SD = 7.9 ) in Y-BOCS score compared with a mean increase in score of 0.54 ( SD = 1.31 ) for subjects in the placebo group ( F = 4.85 , df = 2,23 ; p = .04 ) . Six ( 46 % ) of 13 subjects in the olanzapine group showed a 25 % or greater improvement in Y-BOCS score compared with none in the placebo group . The final mean dose of olanzapine was 11.2 ( SD = 6.5 ) mg/day . Medication was well tolerated . Only 2 ( 15 % ) of 13 subjects who received olanzapine discontinued because of side effects : sedation ( N = 1 ) or weight gain ( N = 1 ) . CONCLUSION These results provide preliminary evidence that adding olanzapine to SRIs is potentially efficacious and well tolerated in the short-term treatment of patients with refractory OCD . Controlled studies with larger sample sizes are necessary to more definitively address this treatment strategy This study aim ed 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 r and omized 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 OBJECTIVE This article describes the long-term effects of augmenting serotonin reuptake inhibitors ( SRIs ) with exposure and ritual prevention or stress management training in patients with DSM-IV obsessive-compulsive disorder ( OCD ) . METHOD Between November 2000 and November 2006 , 111 OCD patients from 2 academic outpatient centers with partial SRI response were r and omized to the addition of exposure and ritual prevention or stress management training , delivered twice weekly for 8 weeks ( acute phase ) ; 108 began treatment . Responders ( 38 of 52 in the exposure and ritual prevention condition , 11 of 52 in the stress management training condition ) entered a 24-week maintenance phase . The Yale-Brown Obsessive Compulsive Scale ( YBOCS ) was the primary outcome measure . RESULTS After 24 weeks , patients r and omized to and receiving exposure and ritual prevention versus stress management training had significantly better outcomes ( mean YBOCS scores of 14.69 and 21.37 , respectively ; t = 2.88 , P = .005 ) , higher response rates ( decrease in YBOCS scores ≥ 25 % : 40.7 % vs 9.3 % , Fisher exact test P < .001 ) , and higher rates of excellent response ( YBOCS score ≤ 12 : 24.1 % vs 5.6 % , Fisher exact test P = .01 ) . During the maintenance phase , the slope of change in YBOCS scores was not significant in either condition ( all P values ≥ .55 ) , with no difference between exposure and ritual prevention and stress management training ( P > .74 ) . Better outcome was associated with baseline variables : lower YBOCS scores , higher quality of life , fewer comorbid Axis I diagnoses , and male sex . CONCLUSIONS Augmenting SRIs with exposure and ritual prevention versus stress management training leads to better outcome after acute treatment and 24 weeks later . Maintenance outcome , however , was primarily a function of OCD severity at entrance . Greater improvement during the acute phase influences how well patients maintain their gains , regardless of treatment condition BACKGROUND Adding the atypical neuroleptic risperidone to a serotonin reuptake inhibitor ( SRI ) has benefited patients with treatment-refractory obsessive-compulsive disorder ( OCD ) . Since olanzapine and risperidone have similar serotonergic and dopaminergic receptor binding profiles , we tested the hypothesis that olanzapine augmentation would be beneficial in treatment-unresponsive OCD . METHOD For this 8-week trial , we recruited 10 adult OCD patients ( DSM-IV criteria ) unresponsive to fluoxetine ( > or = 60 mg/day ) for > or = 10 weeks , which was continued throughout the trial . Other psychotropic medications were discontinued . Subjects had OCD for > or = 1 year , a Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) score of > or = 18 , and no organic , psychotic , or other primary Axis I disorder . Two weeks after olanzapine , 2.5 mg/day , was added , and in the absence of responder status ( Y-BOCS score decrease > or = 25 % ) and limiting side effects , we increased the dose to 5 mg/day , and after 2 more weeks , to 10 mg/day for 4 weeks . RESULTS The subjects had failed a mean of 3.3 SRI trials ( range , 1 - 5 ) and had a mean + /- SD baseline Y-BOCS score of 29.0 + /- 4.9 . Nine patients completed the trial . The subjects ' mean + /- SD endpoint Y-BOCS score was 24.4 + /- 8.0 ( a 16 % decrease ) . The 3 responders ' Y-BOCS scores dropped 68 % , 30 % , and 29 % , but only 1 patient was rated " much improved . " He maintained this improvement during a 6-month follow-up period taking olanzapine , 5 mg/day . Improvement in OCD was independent of improvement in mood symptoms . Six patients ( 60 % ) experienced significant weight gain . CONCLUSION Olanzapine augmentation may benefit treatment-unresponsive OCD . Double-blind , placebo-controlled trials are warranted along with trials comparing risperidone and olanzapine augmentation According to previous data , the addition of risperidone in obsessive-compulsive patients refractory to serotonin reuptake inhibitors ( SRIs ) is shown to be a safe and effective treatment strategy . The aims of our study were to evaluate the efficacy of risperidone addition , in comparison to placebo , in fluvoxamine-refractory obsessive-compulsive patients and to investigate whether risperidone could boost the efficacy of fluvoxamine in fluvoxamine-responder patients . Subjects were 45 obsessive-compulsive in patients , consecutively recruited at the Department of Neurosciences at the San Raffaele Hospital , Milan . Thirty-nine patients completed the study . All patients received 12 weeks of a st and ardized open-label fluvoxamine monotherapy and then continued for 6 weeks with placebo or risperidone in a double-blind design . Results showed a significant effect of risperidone addition , at the end of the double-blind phase ( 18th week ) , only for fluvoxamine-refractory patients . Five patients on risperidone ( 50 % ) and two ( 20 % ) on placebo became responders , with a Yale-Brown Obsessive-Compulsive Scale ( Y-BOCS ) decrease > or = 35 % . Risperidone was generally well tolerated , except for a mild transient sedation and a mild increase in appetite . This preliminary study suggests that even very low ( 0.5 mg ) risperidone doses are effective in OC patients who were nonresponders to a st and ardized treatment with fluvoxamine Objective : Previous studies stressed the role of decision-making functioning in predicting antiobsessive treatment outcome with serotonin reuptake inhibitors drugs in patients with obsessive-compulsive disorder . Nevertheless , the use of an augmentation strategy with atypical antipsychotic drugs has proved to be effective in obsessive-compulsive patients nonresponding to serotonin reuptake inhibitors treatment . We investigated whether the performance at the  Iowa Gambling Task ( IGT ) , a used neuropsychologic task which assesses decision-making , can be an effective criterion for pharmacologic treatment choice in these patients and whether the use of different treatment strategies , according IGT performance , can increase the rate of antiobsessive outcome . Method : Thirty patients with obsessive-compulsive disorder were treated in a single-blind design with fluvoxamine plus placebo or fluvoxamine plus risperidone according to their IGT performance . Treatment outcome was recorded after 6 and 12 weeks . Results : Patients with good IGT performance showed a good antiobsessive treatment outcome with fluvoxamine only , while only adopting an augmentation strategy with risperidone , the number of responders patients within the subjects with bad IGT performance increased . Conclusions : IGT performance may be considered an effective criterion for pharmacologic treatment choice in obsessive-compulsive patients given that antiobsessive treatment outcome is increased to 85 % of responders choosing an appropriate drug strategy according to the IGT performance OBJECTIVE Although atypical antipsychotic agents have been found effective in the augmentation of serotonin reuptake inhibitors ( SRIs ) for treatment-resistant obsessive-compulsive disorder ( OCD ) in short-term trials , there are few data on the effectiveness and safety of these agents in clinical setting s over the long term . METHOD Subjects ( N = 46 ) who responded to selective SRIs ( SSRIs ) in an initial 12-week trial were continued on SSRI monotherapy plus cognitive-behavioral therapy ( CBT ) for 1 year . Subjects ( N = 44 ) who failed to respond to SSRIs were r and omly assigned to 1 of 3 atypical antipsychotics -- olanzapine , quetiapine , or risperidone -- and were consecutively treated using SSRI + atypical antipsychotics combined with CBT for 1 year . This study was conducted from January 2006 to November 2007 at Osaka City University Graduate School of Medicine Hospital , Japan . RESULTS Augmentation with atypical antipsychotics reduced mean + /- SD Yale-Brown Obsessive Compulsive Scale ( YBOCS ) total scores in SSRI-refractory OCD patients ( at initial assessment = 29.3 + /- 9.9 , after 1 year = 19.3 + /- 6.8 ) . However , compared to SSRI responders ( at initial assessment = 25.8 + /- 11.4 , after 1 year = 13.7 + /- 4.6 ) , total YBOCS scores in those who required atypical antipsychotic augmentation were initially higher , and they remained at higher levels than those of SRI responders after 1 year of the treatments . CONCLUSIONS Our work does not sufficiently support the long-term effectiveness of the atypical antipsychotics in the augmentation of SSRIs for treatment-resistant OCD patients . Even though this approach seems useful for some types of OCD patients , such as those with symmetry/ordering and hoarding symptoms , these data emphasize the limitations of the current pharmacotherapeutic options in treatment-refractory OCD , and their chronic use raises a number of safety concerns . TRIAL REGISTRATION ( Clinical Trials.gov ) Identifier NCT00854919 OBJECTIVE This study aim ed to evaluate the efficacy and safety of N-acetylcysteine , a glutamate-modulating agent , in patients with treatment-refractory obsessive-compulsive disorder as an adjunct to serotonin reuptake inhibitor treatment . METHODS Forty-eight patients ( 36 women ; mean ± SD age , 30.93 ± 4.99 ) with obsessive-compulsive disorder who failed to respond to a course of serotonin reuptake inhibitor treatment  were r and omized to a 12-week intervention period of N-acetylcysteine ( up to 2400 mg/d ) or placebo . Primary outcome measures were the change in Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) score from baseline to end point and the rate of full response in each group at the end of trial . Full response was defined as 35 % or greater reduction in Y-BOCS score from baseline . RESULTS Changes of Y-BOCS score were different over time ( P < 0.001 ) and between groups ( P < 0.001 ) . N-acetylcysteine-assigned patients showed significantly improved mean Y-BOCS score ( P = 0.003 ) and Clinical Global Impression-Severity of Illness scale score ( P = 0.01 ) but not Clinical Global Impression-Improvement scale score at study end point . Of the patients in the N-acetylcysteine group , 52.6 % were full responders at the end of the study , which was significantly higher than 15 % of the patients in the placebo group ( P = 0.013 ) . CONCLUSION This trial suggests that N-acetylcysteine may be a safe and effective option to augment st and ard treatment in patients with refractory obsessive-compulsive disorder CONTEXT The extant literature on the treatment of pediatric obsessive-compulsive disorder ( OCD ) indicates that partial response to serotonin reuptake inhibitors ( SRIs ) is the norm and that augmentation with short-term OCD-specific cognitive behavior therapy ( CBT ) may provide additional benefit . OBJECTIVE To examine the effects of augmenting SRIs with CBT or a brief form of CBT , instructions in CBT delivered in the context of medication management . DESIGN , SETTING , AND PARTICIPANTS A 12-week r and omized controlled trial conducted at 3 academic medical centers between 2004 and 2009 , involving 124 pediatric out patients between the ages of 7 and 17 years with OCD as a primary diagnosis and a Children 's Yale-Brown Obsessive Compulsive Scale score of 16 or higher despite an adequate SRI trial . INTERVENTIONS Participants were r and omly assigned to 1 of 3 treatment strategies that included 7 sessions over 12 weeks : 42 in the medication management only , 42 in the medication management plus instructions in CBT , and 42 in the medication management plus CBT ; the last included 14 concurrent CBT sessions . MAIN OUTCOME MEASURES Whether patients responded positively to treatment by improving their baseline obsessive-compulsive scale score by 30 % or more and demonstrating a change in their continuous scores over 12 weeks . RESULTS The medication management plus CBT strategy was superior to the other 2 strategies on all outcome measures . In the primary intention-to-treat analysis , 68.6 % ( 95 % CI , 53.9%-83.3 % ) in the plus CBT group were considered responders , which was significantly better than the 34.0 % ( 95 % CI , 18.0%-50.0 % ) in the plus instructions in CBT group , and 30.0 % ( 95 % CI , 14.9%-45.1 % ) in the medication management only group . The results were similar in pairwise comparisons with the plus CBT strategy being superior to the other 2 strategies ( P < .01 for both ) . The plus instructions in CBT strategy was not statistically superior to medication management only ( P = .72 ) . The number needed-to-treat analysis with the plus CBT vs medication management only in order to see 1 additional patient at week 12 , on average , was estimated as 3 ; for the plus CBT vs the plus instructions in CBT strategy , the number needed to treat was also estimated as 3 ; for the plus instructions in CBT vs medication management only the number needed to treat was estimated as 25 . CONCLUSIONS Among patients aged 7 to 17 years with OCD and partial response to SRI use , the addition of CBT to medication management compared with medication management alone result ed in a significantly greater response rate , whereas augmentation of medication management with the addition of instructions in CBT did not . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00074815
Using the Cochrane methodology , and as measures of effect size mean difference and Hedge 's g , SRIs proved to be superior to drug placebo , with a modest effect size .
From direct comparisons of CBT and SRI treatments , we conclude that CBT has the superior efficacy .
COMBO versus CBT shows that SRI treatment adds little to concomitant CBT , while COMBO shows favourable outcome versus SRI alone .
In pre-trial partial treatment responders , those who failed a SRI had better outcome from adding CBT as compared to continuing a SRI .
Those who failed CBT treatment did as well with continued CBT as with switching to a SRI .
Serotonin reuptake inhibiting drugs ( SRI ) have been used in the treatment of paediatric obsessive-compulsive disorder over the past 30 years .