W Zheng1, Y-T Xiang2,3, Y-Q Xiang4, X-B Li4, G S Ungvari5,6, H F K Chiu7, C U Correll8,9. 1. The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China. zhengwei0702@163.com. 2. The National Clinical Research Center for Mental Disorders, China & Beijing Anding Hospital, Capital Medical University, Beijing, China. xyutly@gmail.com. 3. Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao, China. xyutly@gmail.com. 4. Beijing Anding Hospital, Capital Medical University, Beijing, China. 5. The University of Notre Dame Australia/Marian Centre, Perth, WA, Australia. 6. School of Psychiatry & Clinical Neurosciences, University of Western Australia, Perth, WA, Australia. 7. Department of Psychiatry, Chinese University of Hong Kong, Hong Kong, China. 8. Division of Psychiatry Research, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA. 9. Hofstra Northwell School of Medicine, Hempstead, NY, USA.
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.
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.
Authors: Julie R Larsen; Louise Vedtofte; Mathilde S L Jakobsen; Hans R Jespersen; Michelle I Jakobsen; Camilla K Svensson; Kamuran Koyuncu; Ole Schjerning; Peter S Oturai; Andreas Kjaer; Jimmi Nielsen; Jens J Holst; Claus T Ekstrøm; Christoph U Correll; Tina Vilsbøll; Anders Fink-Jensen Journal: JAMA Psychiatry Date: 2017-07-01 Impact factor: 21.596
Authors: Xiao-Lan Cao; Shi-Bin Wang; Bao-Liang Zhong; Ling Zhang; Gabor S Ungvari; Chee H Ng; Lu Li; Helen F K Chiu; Grace K I Lok; Jian-Ping Lu; Fu-Jun Jia; Yu-Tao Xiang Journal: PLoS One Date: 2017-02-24 Impact factor: 3.240