Comparative efficacy and tolerability of antipsychotics as augmentations in adults with treatment-resistant obsessive-compulsive disorder: A network meta-analysis.

We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of antipsychotics to augment serotonin reuptake inhibitors (SRIs) for treatment-resistant obsessive-compulsive disorder (OCD) in adults. PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched on September 8, 2018. Randomized controlled trials investigating antipsychotics as augmentation agents were included. Network meta-analyses were performed using frequentist methods. Efficacy was measured by the Yale-Brown Obsessive-Compulsive Scale. Tolerability was measured by side-effect discontinuations. Mean differences (MDs) and odds ratios (ORs) were reported with 95% confidence intervals (CIs). Twenty articles with 790 patients were included. Our analyses showed that there was no significant difference in efficacy between antipsychotic agents. The order of efficacy rankings was inconsistent between primary analysis and sensitivity analyses. We found that there was considerable heterogeneity between studies. Comorbid tics was identified as a significant moderator. All antipsychotics except paliperidone were significantly superior to placebo in the subgroup without comorbid tics, while no antipsychotics was significantly superior to placebo in the comorbid tics subgroup. With respect to tolerability, quetiapine (OR, 3.45; 95% CI, 1.04-11.11) and paliperidone (20.00; 1.01->100) were significantly less tolerable than placebo. Based on this network meta-analysis, antipsychotic agents as augmentations to SRIs might be more effective in treatment-resistant OCD patients without comorbid tics. Definitive determination of which drug is optimal cannot be drawn currently because of the limited numbers of studies and heterogeneity across studies.

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

BACKGROUND: Various 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. METHODS: PubMed, 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). RESULTS: Thirty-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. CONCLUSIONS: Our 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.

An updated meta-analysis: Short-term therapeutic effects of repeated transcranial magnetic stimulation in treating obsessive-compulsive disorder.

BACKGROUND: This study was conducted to evaluate the short-term therapeutic effects of using repeated transcranial magnetic stimulation (rTMS) to treat obsessive-compulsive disorder (OCD) and to examine potential influencing factors. METHOD: We searched the PubMed, EMBASE, CENTRAL, Wanfang, CNKI, and Sinomed databases on September 18, 2016 and reviewed the references of previous meta-analyses. Sham-controlled, randomized clinical trials using rTMS to treat OCD were included. Hedge's g was calculated for the effect size. Subgroup analyses and univariate meta-regressions were conducted. RESULTS: Twenty studies with 791 patients were included. A large effect size (g=0.71; 95%CI, 0.55-0.87; P<0.001) was found for the therapeutic effect. Targeting the supplementary motor area (SMA) (g=0.56; 95%CI, 0.12-1.01; P<0.001), left dorsolateral prefrontal cortex (DLPFC) (g=0.47; 95%CI, 0.02-0.93; P=0.02), bilateral DLPFC (g=0.65; 95%CI, 0.38-0.92; P<0.001) and right DLPFC (g=0.93; 95%CI, 0.70-1.15; P<0.001), excluding the orbitofrontal cortex (OFC) (g=0.56; 95%CI, -0.05-1.18; P=0.07), showed significant improvements over sham treatments. Both low-frequency (g=0.73; 95%CI, 0.50-0.96; P<0.001) and high-frequency (g=0.70; 95%CI, 0.51-0.89; P<0.001) treatments were significantly better than sham treatments, with no significant differences between the effects of the two frequencies. The subgroup analyses indicated that patients who were non-treatment resistant, lacked concurrent major depressive disorder (MDD) and received threshold-intensity rTMS showed larger therapeutic effects than the corresponding subgroups. The subgroup analysis according to sham strategy showed that tilted coils yielded larger effects than sham coils. Meta-regression analyses revealed that none of the continuous variables were significantly associated with the therapeutic effects. LIMITATIONS: Only short-term therapeutic effects were assessed in this study. CONCLUSIONS: Based on this study, the short-term therapeutic effects of rTMS are superior to those of sham treatments. The site of stimulation, stimulation frequency and intensity and sham condition were identified as potential factors modulating short-term therapeutic effects. The findings of this study may inspire future research.