Augmentation Of Serotonin Reuptake Inhibitors Research Articles

Predictors of EX/RP alone versus EX/RP with medication for adults with OCD: Does medication status moderate outcomes?

Exposure and response prevention (EX/RP) can be delivered as monotherapy or to augment serotonin reuptake inhibitors (SRIs). While both options are considered effective OCD treatments, responses are heterogenous. Substantial work has investigated EX/RP predictors to account for this variability, with mixed findings. Little research has studied whether EX/RP predictors may differ in medicated versus non-medicated samples (i.e., medication status as a moderator). We pooled data from two clinical trials conducted concurrently in the same specialty OCD clinic. One enrolled patients who were on stable SRI doses (EX/RP as SRI augmentation, n = 58) while the other enrolled non-medicated patients (EX/RP monotherapy, n = 38). Both trials used the same manualized EX/RP protocol and blinded independent evaluators. LASSO regression derived predictors and moderators of outcome. Improvement did not significantly differ between the EX/RP alone group and the SRI + EX/RP group. In both groups, higher baseline OCD severity and worse quality of life predicted poorer outcome. OCPD traits moderated results: Patients with more severe OCPD traits had better outcomes from EX/RP monotherapy than those receiving EX/RP with SRIs. Patient adherence to EX/RP homework mediated the associations between the baseline variables and outcome. The effect of OCPD traits on outcome warrants future study to improve care.

Pharmacological augmentation of serotonin reuptake inhibitors in patients with obsessive-compulsive disorder: A network meta-analysis.

The augmentation of serotonin reuptake inhibitors (SRIs) can be achieved by add-on therapy with different pharmacological agents in obsessive-compulsive disorder (OCD) for a better clinical outcome. This network meta-analysis (NMA) was conducted to evaluate and compare the effects of available augmentation agents for SRIs in OCD. The data was extracted from 59 relevant clinical trials after a literature search on MEDLINE/PubMed, Scopus, Cochrane databases and clinical trial registries. PRISMA guidelines were followed in data extraction, analysis and reporting. Random effects Bayesian NMA was done to pool the effects across the interventions for the change in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scoring from baseline to the end of the study. Network graph was built, consistency model was run, node splitting analysis was performed, treatments were ranked as per SUCRA score and meta-regression was done for refractoriness to SRIs and duration of augmentation therapy as the predictor variables. The drugs showing significant reduction in YBOCS scoring were pregabalin (MD:-8.1;95% CrI: -16, -0.43), memantine (MD:-6.2;95% CrI: -9.9, -2.3), lamotrigine (MD:-6;95% CrI: -12, -0.47), ondansetron (MD:-5.7;95% CrI: -11, -0.67), granisetron (MD:-5.6;95% CrI: -11, -0.44), aripiprazole (MD:-5.4;95% CrI:-9.1, -1.6), risperidone (MD:-3.3;95% CrI: -6.4, -0.20) and topiramate (MD:-5.3;95% CrI: -9.6, -0.97). The node-split analysis showed that direct and indirect pooled effect sizes for all comparisons were comparable. Meta-regression showed a statistically non-significant association between YBOCS score reduction with the duration of augmentation therapy, but significant with SRI-refractory status. Finally, the results were sorted based on certainty of evidence. Memantine was found to be most effective augmentation agent for SRIs in OCD, followed by lamotrigine, ondansetron and granisetron with moderate certainty of evidence. The augmentation agents showed better symptom reduction in patients with SRI-refractory OCD in comparison to non-refractory OCD. CRD42022360110.

Body Dysmorphic Disorder: Clinical Overview and Relationship to Obsessive-Compulsive Disorder.

Body dysmorphic disorder (BDD), characterized by a distressing or impairing preoccupation with nonexistent or slight defects in appearance, is associated with markedly poor quality of life and high rates of suicidality. Onset of BDD is usually in childhood or adolescence and, unless appropriately treated, tends to be chronic. The first-line pharmacologic approach for both delusional and non-delusional BDD is serotonin reuptake inhibitors (SRIs), often at high doses. SRI augmentation and switching strategies can be effective. The first-line psychotherapy is cognitive-behavioral therapy (CBT) tailored to BDD's unique clinical features. Cosmetic treatment (such as surgery or dermatologic treatment), although received by a majority of patients with BDD, is not recommended. BDD has many similarities to obsessive-compulsive disorder (OCD) and appears closely related to OCD but also has some important differences. This article, which updates a 2015 article on BDD that we published in this journal, provides a clinically focused overview of BDD and its relationship to OCD.

A Comparative Study of Aripiprazole, Olanzapine, and L-Methylfolate Augmentation in Treatment Resistant Obsessive-Compulsive Disorder.

About half of the patients with Obsessive-compulsive disorder (OCD) do not respond to serotonin reuptake inhibitors (SRIs) or have a partial improvement in their symptoms. This study aimed to compare the efficiency and safety of aripiprazole, olanzapine, and L-methyl folate in patients with resistant OCD. The study consisted of an open-label prospective phase of 12-weeks to ascertain resistance to SRIs and a second 6-week open-label addition phase for non or, partial responders of the first phase. One-hundred-fifteen patients entered the 16-week open-label phase. Fifty patients (43.47%) responded to the SRIs monotherapy, two patients developed adverse effects and another three were lost to the follow up. Sixty patients (52.2%) were considered treatment-resistant and entered the 6-week open-label aripiprazole, olanzapine, or L-methyl folate addition phase; Patients showed a significant improvement over 6-week study period in olanzapine and aripiprazole group as measured by YBOCS total score (p < 0.001) while there was no change in the L-methyl folate group at the end as compared with baseline (p = 0.150). Clinical Global Impression-Severity decreased from 4.90 to 2.90 in olanzapine and aripiprazole group at the end of 6weeks while there was no change in the L-methyl folate group. The CGI-I was significant in the olanzapine and aripiprazole group (p < 0.001) while it was insignificant in the L-methyl folate group (p = 0.088). Augmentation of SRIs with olanzapine or aripiprazole could be a promising option for resistant OCD. L-methyl folate though shown to be effective in resistant depression was not effective in treatment resistant OCD.

Augmentation With Memantine in Obsessive-Compulsive Disorder.

Patients with obsessive-compulsive disorder (OCD) who do not respond adequately to serotonin reuptake inhibitor (SRI) therapy and cognitive behavioral therapy commonly receive SRI augmentation in the form of an atypical antipsychotic drug. Memantine is another augmentation strategy that has been trialed. A recent systematic review and meta-analysis found very large improvements associated with memantine augmentation in OCD. Specifically, in 4 randomized controlled trials (RCTs), the response rate was 81% in 67 memantine-treated patients vs only 19% in 68 placebo-treated patients. The weighted mean difference between memantine and placebo groups was nearly 8 points on the Yale-Brown Obsessive Compulsive Scale. Such striking differences for intervention vs placebo in a difficult-to-treat disorder demand scrutiny. An examination of the RCTs on which the meta-analysis was based showed that all 4 RCTs emerged from the same geographical area, limiting the generalizability of the findings. Of greater concern, all 4 RCTs presented what were effectively completer analyses of data, compromising the scientific validity of the findings. There were several other concerns about the individual studies and about the meta-analysis, itself. Therefore, a reasonable conclusion is that, when the internal and external validity of studies in a meta-analysis are compromised, the findings and conclusions of the meta-analysis cannot be considered sound. It is concluded that, despite the very large benefits reportedly associated with memantine augmentation, the routine use of memantine as an augmentation agent for OCD cannot as yet be recommended.

Randomized, single blinded comparative study of selective serotonin reuptake inhibitor augmentation with olanzapine v/s amisulpride for obsessive compulsive disorder

Background: Obsessive-Compulsive Disorder is classified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) as an anxiety disorder. Serotonin reuptake inhibitors are considered to be most effective and are the first line pharmacotherapy for the treatment of OCD. However, about 40-60% of OCD patients fail to respond to SSRI mono-therapy. Further, as many as 25% of patients fails to experience any improvement from initial SSRIs mono-therapy. For non-responder’s low dose augmentation with antipsychotics (risperidone, quetiapine, olanzapine, aripirazole, amisuplride etc.) has shown promising response, as compared to serotonin enhancers. The present study is designed to evaluate and compare the efficacy and adverse drug reactions of these two antipsychotics viz. Olanzapine and amisulpride as augmentation strategy in OCD patients. Objective of present study was to compare the efficacy of olanzapine and amisulpride as add on therapy for inadequately controlled obsessive-compulsive disorder patients on selective-serotonin reuptake inhibitor.Methods: the present study was done at Medical College Jabalpur (M.P.) in the department of Psychiatry &amp; Pharmacology. It was randomized, patient blinded study. 47 patients were screened for the study out of which 36 were enrolled and randomized into either SSRI+Olanzapine or SSRI+Amisulpride group. The patients were evaluated at baseline and then biweekly for 12 weeks to assess the efficacy of these drugs as augmentation strategy using Yale-Brown Obsessive Compulsive Scale (Y-BOCS).Results: There was a significant improvement in Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Clinical Global Impression-Severity (CGI-S) score and Clinical Global impression-Improvement (CGI-I) score in both the groups but there was no significant difference (P&gt;0.05) in either of these groups on these three scale. No serious adverse drug reaction was reported in either of these groups.Conclusions: Both olanzapine and amisulpride are efficacious and well tolerated for augmentation of SSRI with no significant difference in their efficacy.

Augmentation agents to serotonin reuptake inhibitors for treatment-resistant obsessive-compulsive disorder: A network meta-analysis

BackgroundVarious agents for augmentation of serotonin reuptake inhibitors have been investigated for treatment-resistant obsessive-compulsive disorder (OCD). We aimed to comprehensively compare different augmentation agents for treatment-resistant OCD in adults. MethodsPubMed, Embase, Web of Science, CENTRAL, the WHO's ICTRP, and ClinicalTrials.gov were searched on February 20, 2018. Pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcome was efficacy measured by the Yale-Brown Obsessive Compulsive Scale. The secondary outcomes were tolerability (side-effect discontinuation) and acceptability (all cause discontinuation). Mean differences (MDs) and odds ratios (ORs) were reported with 95% confidence intervals (CIs). ResultsThirty-three articles with 34 trials (1216 patients) were included. Memantine (MD, −8.94; 95% CI, −14.42 to −3.42), risperidone (−4.47, −8.75 to −0.17), topiramate (−6.05, −10.89 to −1.20), lamotrigine (−6.07, −11.61 to −0.50), and aripiprazole (−5.14, −9.95 to −0.28) were significantly superior to placebo. Antipsychotic (−4.09, −6.22 to −1.93) and glutamatergic (−5.22, −7.53 to −2.84) agents were significantly superior to placebo. Considerable heterogeneity was found across studies, and baseline symptom severity was identified as a significant moderator. After baseline severity adjustment, quetiapine (−5.00, −8.59 to −1.29) and olanzapine (−8.28, −15.34 to −1.13) became significantly superior to placebo. ConclusionsOur study supports the use of antipsychotic or glutamatergic agents as augmentation agents for treatment-resistant OCD. Topiramate, lamotrigine, aripiprazole, olanzapine, risperidone, memantine, and quetiapine are alternative augmentation drugs; however, a definitive conclusion of the best drug remains undetermined because of the considerable heterogeneity and limited numbers of studies and patients for each agent.

P.4.d.003 - Augmentation of serotonin reuptake inhibitors with antipsychotic drugs in treatment-resistant obsessive-compulsive disorder: a meta-analysis

P.4.d.003 - Augmentation of serotonin reuptake inhibitors with antipsychotic drugs in treatment-resistant obsessive-compulsive disorder: a meta-analysis

The effect of treatment on quality of life and functioning in OCD

BackgroundGiven that obsessive compulsive disorder (OCD) is associated with impaired quality of life (QoL) and functioning, it is important examine whether therapeutic recovery from OCD leads to improvements on these important secondary outcomes. Only a few studies have examined how measures of OCD symptom severity relate to QoL and functioning among patients receiving treatment for OCD. MethodsOCD severity was measured with the Obsessive–Compulsive Inventory-Revised (OCI-R), a self-report scale of OCD, and the Yale–Brown Obsessive Compulsive Scale (Y-BOCS), an interview measure of OCD. Participants were 100 adults with a primary diagnosis of OCD on serotonin reuptake inhibitors (SRIs) enrolled in a randomized clinical trial comparing SRI augmentation with either exposure and response prevention (EX/RP) therapy, risperidone, or pill placebo. At baseline, mid-treatment, and post-treatment, patients completed assessments for OCD symptoms and QoL/functioning measures. Multilevel modeling was used to assess changes in QoL/functioning over the course of treatment and to compare such changes across treatment conditions. ResultsImprovements in QoL/functioning were significantly greater among those receiving EX/RP compared to those receiving risperidone. Compared to pill placebo, EX/RP performed better on measures of functioning but not QoL. Greater improvement in individual OCI-R scores was associated with greater improvements in QoL/functioning, regardless of condition. In addition, Y-BOCS scores appeared to moderate improvements in QoL over the course of all treatment conditions, such that those with higher Y-BOCS scores showed the greatest improvements in QoL over time. ConclusionsImprovements in QoL/functioning were associated with reduction in OCD symptom severity. The implications on OCD treatment and clinical research are discussed.

Patient adherence and treatment outcome with exposure and response prevention for OCD: Which components of adherence matter and who becomes well?

Exposure and response prevention (EX/RP) is an evidence-based treatment for obsessive-compulsive disorder (OCD), yet not all patients achieve wellness with EX/RP. The degree to which patients adhere to EX/RP procedures outside of sessions has been found to predict therapy outcomes, including who achieves post-treatment wellness. We sought to investigate which components of treatment adherence most relate to outcome and to develop adherence benchmarks to identify who does and does not become well to provide clinicians with prognostic tools. Adherence data came from 37 adult patients with DSM-IV OCD who received 17 sessions of EX/RP as part of a randomized controlled trial of augmentation strategies for incomplete response to serotonin reuptake inhibitors (SRIs). Therapists rated between-session patient adherence at each exposure session by quantifying: 1) the quantity of homework exposures attempted; 2) the quality of attempted exposures; and 3) the degree of success with response prevention. Each adherence item significantly correlated with post-treatment OCD severity. Success with response prevention proved particularly strongly linked to therapy outcome. Time course analysis of this item accurately identified, relatively early in treatment, who would achieve post-treatment wellness. These data provide an efficient method for differentiating between those patients who will and will not achieve wellness after EX/RP augmentation of SRIs. Limitations and clinical implications of the current findings are discussed.

Exposure and Response Prevention Helps Adults With Obsessive-Compulsive Disorder Who Do Not Respond to Pharmacological Augmentation Strategies

Serotonin reuptake inhibitors (SRIs) are a first-line treatment for obsessive-compulsive disorder (OCD). Yet, most patients with OCD who are taking SRIs do not show excellent response. Recent studies show that augmenting SRIs with risperidone benefits a minority of patients. We evaluated the effectiveness of exposure and response prevention (EX/RP) among nonresponders to SRI augmentation with 8 weeks of risperidone or placebo. The study was conducted from January 2007 to August 2012. Nonresponders to SRI augmentation with risperidone or pill placebo (N = 32) in a randomized controlled trial for adults meeting DSM-IV-TR criteria for OCD were offered up to 17 twice-weekly EX/RP sessions. Independent evaluators, blind to treatment, evaluated patients at crossover baseline (week 8), midway through crossover treatment (week 12), post-EX/RP treatment (week 16), and follow-up (weeks 20, 24, 28, and 32). The primary outcome was OCD severity, measured with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Secondary outcomes were depression, quality of life, insight, and social functioning. Between crossover baseline and follow-up, nonresponders to SRI augmentation with risperidone or placebo who received EX/RP showed significant reductions in OCD symptoms and depression, as well as significant increases in insight, quality of life, and social functioning (all P < .001). Exposure and response prevention is an effective treatment for patients who have failed to respond to SRI augmentation with risperidone or placebo. This study adds to the body of evidence supporting the use of EX/RP with patients who continue to report clinically significant OCD symptoms after multiple pharmacologic trials. ClinicalTrials.gov Identifier: NCT00389493.

Augmenting serotonin reuptake inhibitors in obsessive-compulsive disorder: What moderates improvement?

Patients with obsessive-compulsive disorder (OCD) often only partially respond to serotonin reuptake inhibitors (SRIs). In such cases, American Psychiatric Association practice guidelines suggest augmenting SRIs with cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP) or antipsychotic medication (i.e., risperidone). We examined moderators and predictors of these 2 augmentation strategies. Data came from a randomized controlled trial that compared adding EX/RP or risperidone to SRIs in adults with OCD. Patients entered the study on a stable SRI dosage and were randomized to EX/RP (N = 40), risperidone (N = 40), or placebo (N = 20). Data were analyzed using multilevel modeling. Pretreatment OCD severity, age, and depression were significant moderators. Although OCD severity was unrelated to EX/RP response, individuals with more severe OCD had poorer outcomes and slower improvement with risperidone. Increasing age predicted better response to risperidone, but not EX/RP. Increased depression predicted poorer response to placebo, but not EX/RP or risperidone. Poorer functioning predicted worse outcome across all 3 conditions. Together, these moderators and predictor accounted for 33% of the variance in outcomes, above and beyond the 30.8% accounted for by treatment condition. SRI augmentation with EX/RP was more effective than risperidone across all of the demographic and clinical variables tested. EX/RP's superiority over risperidone increased with baseline OCD severity and with younger age. These data indicate that EX/RP should be the recommended SRI augmentation strategy, even for severe OCD. What determines the degree of EX/RP response in individual patients deserves further study.

P.4.d.006 Serotonin reuptake inhibitor augmentation with n-acetylcysteine in treatment resistant ocd: a double-blind randomized controlled trial

P.4.d.006 Serotonin reuptake inhibitor augmentation with n-acetylcysteine in treatment resistant ocd: a double-blind randomized controlled trial

A meta-analysis of the response of pathological hoarding to pharmacotherapy

This meta-analysis aimed to identify all studies that have assessed treatment response for pathological hoarding treated with pharmacological agents. Seven studies were identified with a total of 92 participants. Most participants had a diagnosis of obsessive-compulsive disorder. Studies assessed response to serotonin-reuptake inhibitors (SRIs); venlafaxine; methylphenidate; and augmentation of SRIs with quetiapine, minocycline and naltrexone. More than half (ER=0.58, 95% CI=0.37–0.76) of the participants treated with pharmacotherapy responded. This study encourages us to consider the use of SRIs in patients with hoarding disorder. The study also encourages more studies of pharmacotherapy for pathological hoarding, noting that these studies should use validated outcome measures that specifically assess pathological hoarding and novel agents that target the unique neurobiological correlates of pathological hoarding.

Serotonin reuptake inhibitor augmentation with N-Acetylcysteine in treatment resistant Obsessive-Compulsive Disorder: a double-blind randomized controlled tribal

Serotonin reuptake inhibitor augmentation with N-Acetylcysteine in treatment resistant Obsessive-Compulsive Disorder: a double-blind randomized controlled tribal

Antipsychotic Augmentation of Serotonin Reuptake Inhibitors in Treatment-Resistant Obsessive-Compulsive Disorder: An Update Meta-Analysis of Double-Blind, Randomized, Placebo-Controlled Trials.

Background:Many patients with obsessive-compulsive disorder do not respond adequately to serotonin reuptake inhibitors. Augmentation with antipsychotic drugs can be beneficial in this regard. However, since new relevant randomized controlled trials evaluating new antipsychotics were conducted, a recalculation of the effect sizes appears necessary.Methods:We meta-analyzed all double-blind, randomized, placebo-controlled trials comparing augmentation of serotonin reuptake inhibitors with antipsychotics to placebo supplementation in treatment-resistant obsessive-compulsive disorder. The primary outcome was mean change in the Yale-Brown Obsessive–Compulsive Scale total score. Secondary outcomes were obsessions, compulsions, response rates, and attrition rates. The data collection process was conducted independently by 2 authors. Hedges’s g and risks ratios were calculated as effect sizes. In preplanned meta-regressions, subgroup analyses, and sensitivity analyses, we examined the robustness of the results and explored reasons for potential heterogeneity.Results:Altogether, 14 double-blind, randomized, placebo-controlled trials (n=491) investigating quetiapine (N=4, n=142), risperidone (N=4, n=132), aripiprazole (N=2, n=79), olanzapine (N=2, n=70), paliperidone (N=1, n=34), and haloperidol (N=1, n=34) were incorporated. Augmentation with antipsychotics was significantly more efficacious than placebo in Yale-Brown Obsessive–Compulsive Scale total reduction (N=14, n=478; Hedges’s g=-0.64, 95% CI: -0.87 to -0.41; P=<.01). Aripiprazole (Hedges’s g=-1.35), haloperidol (Hedges’s g=-0.82), and risperidone (Hedges’s g=-0.59) significantly outperformed placebo. Antipsychotics were superior to placebo in treating obsessions, compulsions, and achieving response. There was no between-group difference concerning all-cause discontinuation. The nonsignificant meta-regressions suggest no influence of the antipsychotic dose or baseline symptom severity on the meta-analytic results.Conclusions:According to our findings, antipsychotic augmentation of serotonin reuptake inhibitors can be regarded as an evidence-based measure in treatment-resistant obsessive-compulsive disorder.

Evaluation of the Efficacy of Antipsychotic Drugs in Sri-resistant Obsessive-compulsive Disorder

Background In a previous meta-analysis investigating pharmacological treatment options in obsessive-compulsive disorder (OCD) we determined a significant efficacy for the augmentation of serotonin reuptake inhibitors (SRIs) with antipsychotic drugs. Because new relevant double-blind, randomized, placebo-controlled trials (DB-RCTs) evaluating new antipsychotics were conducted, we updated our meta-analysis. Methods We included all DB-RCTs that compared augmentation of SRIs with antipsychotics to placebo augmentation in SRI-resistant OCD. Meta-analytic outcomes were treatment response defined by 35% reduction in Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) total score and mean changes in Y-BOCS total score. Effect sizes were standardized mean differences (SMD) and risk ratios (RR). Results Fourteen DB-RCTs (n=467) investigating quetiapine (N=5, n=178), risperidone (N=3, n=72), aripiprazole (N=2, n=79),olanzapine (N=2, n=70), haloperidol (N=1, n=34), and paliperidone (N=1, n=34) were incorporated. The pooled antipsychotic augmentation group was significantly superior to the placebo group in terms of response rates (N=14,n=467; RR=1.98, 95% CI: 1.23 to 3.19;p=0.005) and mean change in Y-BOCS total score (N=14, n=465, SMD=-0.6, 95% CI: -0.97 to -0.23; p=0.002). Concerning the individual antipsychotics, aripiprazole and risperidone significantly outperformed placebo in terms of both responder rates and mean Y-BOCS change. Olanzapine, paliperidone, and quetiapine were not significantly different from the control group. There was no significant heterogeneity and no evidence for publication bias. Conclusions Aripiprazole and risperidone augmentation of SRIs canbe regarded as evidence-based treatment options in treatment-resistant OCD and showed superiority over olanzapine, paliperidone, and quetiapine. About one third of all SRI-resistant OCD subjects responded to augmentation with antipsychotic drugs.

Ondansetron augmentation of serotonin reuptake inhibitors as a treatment strategy in obsessive-compulsive disorder.

Serotonin reuptake inhibitors (SRIs) are the mainstay in the treatment of obsessive-compulsive disorder (OCD). Patients who do not respond adequately to SRIs commonly receive augmentation therapy with another agent, usually an atypical antipsychotic drug. Atypical antipsychotics, however, may not be appropriate for or acceptable to all patients. Ondansetron is an experimental alternative for such patients. There have been at least 6 trials that have examined a short-term (8-12 weeks) role for ondansetron in patients with OCD. These include 1 placebo-controlled crossover trial (N = 11); 1 uncontrolled monotherapy trial (N = 8); 2 low-dose (0.5-1.0 mg/d), uncontrolled augmentation trials in patients who did not respond adequately to ongoing or earlier treatments (pooled N = 35); and 2 moderate- to high-dose (4-8 mg/d) randomized, placebo-controlled augmentation trials in patients with undocumented past treatment history (pooled N = 88). Ondansetron was modestly effective in the uncontrolled trials and strikingly effective in the controlled trials. Ondansetron was also very well tolerated in all of the studies. These enthusiastic observations must be tempered by the limitations of the reviewed data, such as small sample sizes, short study durations, lack of data on the effects of blinded ondansetron discontinuation, lack of long-term data, and study-specific limitations. At best, ondansetron (1-8 mg/d) may be considered an experimental SRI augmentation agent in OCD patients for whom augmentation with an atypical antipsychotic drug is problematic.

Cognitive-Behavioral Therapy vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is one of the world's most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP). To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD. A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial. While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity. Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vs risperidone: mean [SE], -9.72 [1.38]; P < .001 vs placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life. Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile. clinicaltrials.gov Identifier: NCT00389493.

P.4.d.002 Effect of ziprasidone augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive–compulsive disorder

P.4.d.002 Effect of ziprasidone augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive–compulsive disorder