title: Quetiapine augmentation of SRIs in treatment refractory obsessive-compulsive disorder: a double-blind, randomised, placebo-controlled study [ISRCTN83050762] Risperidone and haloperidol augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder: a crossover study. Components of variance and intraclass correlations for the design of community-based surveys and intervention studies: data from the Health Survey for England 1994. 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 A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder Augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder using adjunctive olanzapine: a placebo-controlled trial. Low-dose risperidone augmentation of fluvoxamine treatment in obsessive-compulsive disorder: a double-blind, placebo-controlled study 8-week, single-blind, randomized trial comparing risperidone versus olanzapine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive–compulsive disorder A long-term trial of the effectiveness and safety of atypical antipsychotic agents in augmenting SSRI-refractory obsessive-compulsive disorder. A double-blind, randomized, placebo-controlled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors. Quetiapine addition to serotonin reuptake inhibitor treatment in patients with treatment-refractory obsessive-compulsive disorder: an open-label study. Risperidone augmentation in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. Olanzapine augmentation for treatment-resistant obsessive-compulsive disorder. Quetiapine augments the effect of citalopram in non-refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled study of 76 patients. Adding quetiapine to SRI in treatment-resistant obsessive–compulsive disorder: a randomized controlled treatment study Quetiapine augmentation of serotonin reuptake inhibitors in obsessive-compulsive disorder Quetiapine augmentation in patients with treatment resistant obsessive–compulsive disorder: a single-blind, placebo-controlled study Olanzapine augmentation of paroxetine-refractory obsessive-compulsive disorder The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials
abstract: Background Although serotonin reuptake inhibitors are effective in the treatment of OCD , many patients fail to respond to these agents . Growing evidence from open-label and placebo-controlled trials suggests a role for augmentation of SRIs with atypical antipsychotics in OCD . Quetiapine is generally well tolerated and previous open-label data has produced mixed results in OCD and additional controlled data is needed . Methods We undertook a double-blind , r and omised , parallel-group , flexible-dose , placebo-controlled study of quetiapine augmentation in subjects who had responded inadequately to open-label treatment with an SRI for 12 weeks . Following informed consent and screening , forty-two subjects were r and omised to either placebo or quetiapine for six weeks . Results There was significant improvement from baseline to endpoint on the Yale-Brown Obsessive-Compulsive Scale in both the quetiapine and placebo groups ( quetiapine , n = 20 , p < 0.0001 ; placebo , n = 21 , p = 0.001 ) with 40 % ( n = 8) of quetiapine and 47.6 % ( n = 10 ) of placebo treated subjects being classified as responders . Quetiapine did not demonstrate a significant benefit over placebo at the end of the six-week treatment period ( p = .636 ) . Similarly quetiapine failed to separate from placebo in the subgroup of subjects ( n = 10 ) with co-morbid tics . Quetiapine was generally well tolerated . Conclusions In this study , quetiapine augmentation was no more effective than placebo augmentation of SRIs . A number of limitations in study design make comparisons with previous studies in this area difficult and probably contributed to our negative findings . Future work in this important clinical area should address these limitations 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 The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more .  ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas 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 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 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 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 The aim of the present pilot study was to investigate in a single-blind manner , over a period of 8 weeks , the comparative efficacy and tolerability of risperidone versus olanzapine addition in the treatment of OCD patients who did not show a > or=35 % decrease in the YBOCS score after 16-week SRI treatment ( defined as resistant ) . The study consisted of two different phases : a 16-week open-label prospect i ve phase to ascertain resistance to SRI treatment and an 8-week single-blind addition phase for resistant subjects only . Ninety-six subjects with DSM-IV OCD ( YBOCS > or=16 ) entered the open-label prospect i ve phase ; at the end of the 16-week period , 50 ( 52 % ) were judged to be resistant and were r and omized to receive risperidone ( 1 to 3 mg/d ) or olanzapine ( 2.5 to 10 mg/d ) addition for 8 weeks . Overall , patients in both groups responded significantly , without differences between the two treatment groups ; although no differences emerged for the proportion of patients reporting at least an adverse event , the profiles of adverse experiences differed significantly , being risperidone associated with amenorrhoea and olanzapine with weight gain 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 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 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 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 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 OBJECTIVE To assess the efficacy of quetiapine addition to citalopram in treatment-naive or medication-free obsessive-compulsive disorder ( OCD ) patients . METHOD Seventy-six patients who met DSM-IV criteria for OCD and who were drug-free or drug-naive at entry were r and omly assigned in a 10-week , double-blind trial with citalopram ( 60 mg/day ) plus quetiapine ( 300 - 450 mg/day ) or placebo ;  treatment-refractory OCD patients were excluded . Of the 76 eligible patients , 66 patients completed the trial-31 in the quetiapine and 35 in the placebo group . The change from baseline to endpoint on the total Yale-Brown Obsessive Compulsive Scale ( YBOCS ) and the response to treatment in the quetiapine addition compared with the placebo addition group were the primary outcome measures . Response was defined as a 35 % or greater reduction on the YBOCS and a Clinical Global Impressions-Improvement ( CGI-I ) score at endpoint of 1 or 2 . The study was conducted from November 2003 to June 2005 at the University Medical Centre Utrecht , The Netherl and s. RESULTS As measured by the mean reduction in YBOCS scores following an intent-to-treat , last-observation-carried-forward analysis , quetiapine addition ( 11.9 ) was significantly superior to placebo ( 7.8 ; p = .009 ) . Quetiapine addition was also significantly superior to placebo on the CGI-I scale , with a mean + /- SD CGI-I score of 2.1 + /- 1.3 versus 1.4 + /- 1.2 , respectively ( p = .023 ) . Quetiapine addition ( N = 22 , 69 % ) was also associated with a significantly greater number of patients responding to treatment compared with placebo addition ( N = 15 , 41 % ; p = .019 ) . More patients receiving quetiapine ( N = 8) than placebo ( N = 2 ; NS ) discontinued treatment due to adverse events . CONCLUSIONS The combination of quetiapine and citalopram was more effective than citalopram alone in reducing OCD symptoms in treatment-naive or medication-free OCD patients . TRIAL REGISTRATION www.trialregister.nl Identifier NTR116 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 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 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 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 To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results
target: Two trials examined olanzapine and found no difference in the primary outcome ( response to treatment ) and most other efficacy-related outcomes but it was associated with more weight gain than monotherapy with antidepressants .
  There were also some beneficial effects of quetiapine in terms of anxiety or depressive symptoms .
background: BACKGROUND Obsessive compulsive disorder ( OCD ) is a psychiatric disorder which has been shown to affect 2 to 3.5 % of people during their lifetimes .
  Inadequate response occurs in 40 % to 60 % of people that are prescribed first line pharmaceutical treatments ( selective serotonin reuptake inhibitors ( SSRIs ) ) .
  To date not much is known about the efficacy and adverse effects of second-generation antipsychotic drugs ( SGAs ) in people suffering from OCD .
  OBJECTIVES To evaluate the effects of SGAs ( monotherapy or add on ) compared with placebo or other forms of pharmaceutical treatment for people with OCD .