title: Efficacy and safety of adjunctive topiramate for schizophrenia: a meta-analysis of randomized controlled trials.
abstract: To systematically examine the randomized controlled trial (RCT) evidence regarding efficacy and tolerability of topiramate cotreatment with antipsychotics in schizophrenia-spectrum disorders.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China. zhengwei0702@163.com.
authors: W
authors: W
authors: Zheng
authors: The National Clinical Research Center for Mental Disorders, China & Beijing Anding Hospital, Capital Medical University, Beijing, China. xyutly@gmail.com.|Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao, China. xyutly@gmail.com.
authors: Y-T
authors: YT
authors: Xiang
authors: Beijing Anding Hospital, Capital Medical University, Beijing, China.
authors: Y-Q
authors: YQ
authors: Xiang
authors: Beijing Anding Hospital, Capital Medical University, Beijing, China.
authors: X-B
authors: XB
authors: Li
authors: The University of Notre Dame Australia/Marian Centre, Perth, WA, Australia.|School of Psychiatry & Clinical Neurosciences, University of Western Australia, Perth, WA, Australia.
authors: G S
authors: GS
authors: Ungvari
authors: Department of Psychiatry, Chinese University of Hong Kong, Hong Kong, China.
authors: H F K
authors: HF
authors: Chiu
authors: Division of Psychiatry Research, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA.|Hofstra Northwell School of Medicine, Hempstead, NY, USA.
authors: C U
authors: CU
authors: Correll
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*; D000077236:Topiramate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D000077236:Topiramate; D005632:Fructose
keywords: antipsychotic; meta-analysis; metabolic abnormalities; topiramate; weight gain