Quetiapine Addition to Serotonin Reuptake Inhibitors in Patients With Severe Obsessive-Compulsive Disorder: A Double-Blind, Randomized, Placebo-Controlled Study Quetiapine augmentation of serotonin reuptake inhibitors in obsessive-compulsive disorder Augmentation strategy with olanzapine in resistant obsessive compulsive disorder: an Italian long-term open-label study S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Quetiapine addition to serotonin reuptake inhibitor treatment in patients with treatment-refractory obsessive-compulsive disorder: an open-label study. Amisulpiride augmentation in treatment resistant obsessive-compulsive disorder: an open trial. Adding quetiapine to SRI in treatment-resistant obsessive–compulsive disorder: a randomized controlled treatment study A long-term trial of the effectiveness and safety of atypical antipsychotic agents in augmenting SSRI-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder. The effect of gastric bypass on the pharmacokinetics of serotonin reuptake inhibitors. Quetiapine augmentation of SRIs in treatment refractory obsessive-compulsive disorder: a double-blind, randomised, placebo-controlled study [ISRCTN83050762] A double-blind, randomized, placebo-controlled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors. Depression and Serotonin Reuptake Inhibitor Treatment as Risk Factors for Preterm Birth Risperidone augmentation in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. Augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder using adjunctive olanzapine: a placebo-controlled trial. Risperidone and haloperidol augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder: a crossover study. Reactivity of serotonin in whole blood: relationship with drug response in obsessive-compulsive disorder
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 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 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 OBJECTIVE Despite the progressive increase in the number of antidepressants , many patients with major depressive disorder continue to be symptomatic . Clearly , there is an urgent need to develop better tolerated and more effective treatments for this disorder . The use of S-adenosyl methionine ( SAMe ) , a naturally occurring molecule that serves as a methyl donor in human cellular metabolism , as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development . METHOD Participants were 73 serotonin reuptake inhibitor ( SRI ) nonresponders with major depressive disorder enrolled in a 6-week , double-blind , r and omized trial of adjunctive oral SAMe ( target dose : 800 mg/twice daily ) . Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial . The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale ( HAM-D ) . RESULTS The HAM-D response and remission rates were higher for patients treated with adjunctive SAMe ( 36.1 % and 25.8 % , respectively ) than adjunctive placebo ( 17.6 % versus 11.7 % , respectively ) . The number needed to treat for response and remission was approximately one in six and one in seven , respectively . There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason ( 20.6 % versus 29.5 % , respectively ) , due to adverse events ( 5.1 % versus 8.8 % , respectively ) , or due to inefficacy ( 5.1 % versus 11.7 % , respectively ) . CONCLUSIONS These preliminary results suggest that SAMe can be an effective , well-tolerated , and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication 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 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 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 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 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 Morbidly obese patients frequently present with mood and anxiety disorders , which are often treated with serotonin reuptake inhibitors ( SRIs ) . Having observed that patients treated with SRIs frequently relapse after Roux-en-Y gastric bypass surgery , the authors sought to assess whether SRI bioavailability is reduced postoperatively . METHOD Twelve gastric bypass c and i date s treated with an SRI for primary mood or anxiety disorders were studied prospect ively . Timed blood sample s for  SRI plasma levels were drawn for pharmacokinetic studies before surgery and 1 , 6 , and 12 months afterward . Maximum concentration , time to maximum concentration , and area under the concentration/time curve ( AUC ) were determined . RESULTS In eight of the 12 patients , AUC values 1 month after surgery dropped to an average of 54 % ( SD=18 ) of preoperative levels ( range=36%-80 % ) ; in six of these patients , AUC values returned to baseline levels ( or greater ) by 6 months . Four patients had an exacerbation of depressive symptoms , which resolved by 12 months in three of them . Three of the four patients had a reduced AUC level at 1 month and either gained weight or failed to lose weight between 6 and 12 months . Normalization of the AUC was associated with improvement in symptom scores . CONCLUSIONS Patients taking SRIs in this study were at risk for reduced drug bioavailability 1 month after Roux-en-Y gastric bypass . The authors recommend close psychiatric monitoring after surgery 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 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 Background : Major depressive disorder and the use of serotonin reuptake inhibitors ( SRIs ) in pregnancy have been associated with  preterm birth . Studies that have attempted to separate effects of illness from treatment have been inconclusive . We sought to explore the separate effects of SRI use and major depressive episodes in pregnancy on risk of preterm birth . Methods : We conducted a prospect i ve cohort study of 2793 pregnant women , over sample d for a recent episode of major depression or use of an SRI .  We extracted data on birth outcomes from hospital charts and used binary logistic regression to model preterm birth ( < 37 weeks ' gestation ) . We used ordered logistic regression to model early ( < 34 weeks ' gestation ) or late ( 34–36 weeks ) preterm birth , and we used nominal logistic regression to model preterm birth antecedents ( spontaneous preterm labor/preterm premature rupture of membranes/preterm for medical indications/term ) . Results : Use of an SRI , both with ( odds ratio = 2.1 [ 95 % confidence interval = 1.0–4.6 ] ) and without ( 1.6 [ 1.0–2.5 ] ) a major depressive episode , was associated with preterm birth . A major depressive episode without SRI use ( 1.2 [ 0.68–2.1 ] ) had no clear effect on preterm birth risk . None of these exposures was associated with early preterm birth . Use of SRIs in pregnancy was associated with increases in spontaneous but not medically indicated preterm birth . Conclusions : SRI use increased risk of preterm birth . Although the effect of a major depressive episode alone was unclear , symptomatic women undergoing antidepressant treatment had elevated risk 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 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 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 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
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 .