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Objective We aimed to explore whether the prevalence of manic switch was underestimated in randomized controlled trials ( RCTs) compared to observational studies ( OSs). Method Meta-analyses and simple and systematic reviews were identified by two reviewers in a blinded, standardized manner. All relevant references were extracted to include RCTs and OSs that provided data about manic switch prevalence after antidepressant treatment for a major depressive episode. The primary outcome was manic switch prevalence in the different arms of each study. A meta-regression was conducted to quantify the impact of certain variables on manic switch prevalence. Results A total of 57 papers (35 RCTs and 22 OSs) were included in the main analysis. RCTs underestimated the rate of manic switch [0.53 (0.32-0.87)]. Overestimated prevalence was related to imipraminics [1.85 (1.22-2.79)]; to serotonin-norepinephrine reuptake inhibitors [1.74 (1.06-2.86)]; and to other classes of drugs [1.58 (1.08-2.31)], compared to placebo treatment. The prevalence of manic switch was lower among adults than among children [0.2 (0.07-0.59)]; and higher [20.58 (8.41-50.31)] in case of bipolar disorder. Conclusion Our results highlight an underestimation of the rates of manic switch under antidepressants in RCTs compared to the rates observed in observational studies. [ABSTRACT FROM AUTHOR]

Objective To systematically examine the randomized controlled trial ( RCT) evidence regarding efficacy and tolerability of topiramate cotreatment with antipsychotics in schizophrenia-spectrum disorders. Methods Random-effects meta-analysis of RCTs of topiramate cotreatment with antipsychotics vs. placebo/ongoing antipsychotic treatment in schizophrenia-spectrum disorders. Standardized or weighted mean difference ( SMD/ WMD), risk ratio ( RR) ±95% confidence intervals ( CIs), and number needed to harm ( NNH) were calculated. Results Across 16 RCTs ( n = 934, duration = 11.8 ± 5.6 weeks), topiramate outperformed the comparator regarding change/endpoint of total ( SMD: −0.58, 95% CI: −0.82, −0.35, P < 0.00001), positive ( SMD: −0.37, 95% CI: −0.61, −0.14, P = 0.002), negative ( SMD: −0.58, 95% CI: −0.87, −0.29, P < 0.0001), and general symptoms ( SMD: −0.68, 95% CI: −0.95, −0.40, P < 0.00001). Furthermore, topiramate was superior regarding body weight ( WMD: -2.75 kg, 95% CI: −4.03, −1.47, P < 0.0001), body mass index ( BMI) ( WMD: -1.77, 95% CI: −2.38, −1.15, P < 0.00001), triglycerides ( P = 0.006), and insulin levels ( P < 0.00001). Superiority regarding psychopathology and body weight/ BMI was consistent across Chinese/Asian and Western RCTs, double-blind and open designs, clozapine and non-clozapine cotreatment, augmentation and co-initiation RCTs, and higher and lower quality RCTs. In meta-regression analyses, topiramate's efficacy for total symptoms was moderated by shorter illness duration ( P = 0.047), while weight loss was greater in prevention/co-initiation vs. intervention/augmentation RCTs (−4.11 kg, 95% CI: −6.70, −1.52 vs. −1.41 kg, 95% CI: −2.23, −0.59, P < 0.001). All-cause discontinuation was similar between topiramate and comparators (RR: 1.28, 95% CI: 0.91, 1.81, P = 0.16). While topiramate led to more concentration/attention difficulties ( P = 0.03, NNH = 8, 95% CI=4-25), psychomotor slowing ( P = 0.02, NNH = 7, 95% CI = 4-25), and paresthesia ( P = 0.05, NNH = 2, 95% CI = 4-33), it led to less ≥7% weight gain ( P = 0.0001, NNH = 2, 95% CI = 2-3) and constipation ( P = 0.04, NNH = 9, 95% CI = 5-100) than the comparator. Conclusions These results indicate that adjunctive topiramate to antipsychotics is an effective and safe treatment choice for symptomatic improvement and weight reduction in patients with schizophrenia-spectrum disorders. [ABSTRACT FROM AUTHOR]

Objective To detail the disconnect between the quantified efficacy of the mood stabilizer lamotrigine in its registration controlled trials and its later judged clinical effectiveness and consider some determinants of disconnects between some efficacy trial findings and 'real-world' clinical effectiveness judgments. Method Published articles considering lamotrigine as a treatment for the bipolar I or II disorders were selected for review. While randomized controlled trials were weighted, we also consider open trials and effectiveness observations from clinician researchers and demonstrate that lamotrigine has been quite variably judged over time. Results We suggest that the early trials evaluating lamotrigine for acute bipolar disorder depression focused on a suboptimal clinical target, and in so doing, ensured less lamotrigine efficacy compared with trials of bipolar disorder preventative treatment. Moreover, a number of additional methodological limitations compromised analyses. We also detail variable reporting of actual study results. The initial sharp disconnect (between efficacy and effectiveness judgments) has narrowed as lamotrigine has been evaluated and progressively taken up as a maintenance mood stabilizer. Conclusion The lamotrigine disconnect story provides a number of salutary lessons that are salient to evaluating the effectiveness and ecological niche of any psychotropic medication. The lamotrigine story presented here argues strongly for the wisdom of encouraging an iterative process between efficacy studies and clinical observation. [ABSTRACT FROM AUTHOR]

Objective: Subthreshold depression has a considerable impact on the quality of life and carries a high risk of developing major depressive disorder. Psychological treatments for subthreshold depression may be able to reduce depressive symptomatology and prevent the onset of major depression. Method: We conducted a meta-analysis of randomized controlled studies examining the effects of psychological treatments for subthreshold depression. We examined the effects on depressive symptoms and the preventive effects on the incidence of major depression. Results: Seven high-quality studies with a total of 700 subjects were included. The mean effect size at post-test was 0.42 (95% CI: 0.23–0.60), with very low heterogeneity. The relative risk of developing a major depressive disorder in subjects who received the intervention was 0.70 (95% CI: 0.47–1.03; P = 0.07). Conclusion: Psychological treatments have significant effects on subthreshold depression. Furthermore, these interventions may prevent the onset of major depression. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of an intensive group cognitive treatment (IGCT) to individual cognitive therapy (ICT) and treatment as usual (TAU) in social phobia (DSM-IV). Method: Hundred patients were randomized to: IGCT involving 16 group sessions spread over three weeks; ICT involving 16 shorter weekly sessions in 4 months and; TAU involving an indicated selective serotonin reuptake inhibitor (SSRI) with therapy sessions as required for 1 year. The main outcome measure was a Social Phobia Composite that combined several standardized self-report measures. Diagnostic assessment was repeated at 1-year follow-up. Results: Significant improvements were observed with all treatments. ICT was superior to IGCT and TAU, which did not differ in overall effectiveness. Conclusion: The study confirms and extends previously reported findings that ICT is more effective than group cognitive treatment and treatment with SSRIs. IGCT lasts only 3 weeks, and is as effective as more protracted TAU. [ABSTRACT FROM AUTHOR]