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Efficacy and safety of adjunctive topiramate for schizophrenia: a meta-analysis of randomized controlled trials.

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    • Abstract:
      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]
    • Abstract:
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