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
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
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 .