title: Efficacy for Psychopathology and Body Weight and Safety of Topiramate-Antipsychotic Cotreatment in Patients With Schizophrenia Spectrum Disorders: Results From a Meta-Analysis of Randomized Controlled Trials.
abstract: To meta-analyze the efficacy and tolerability of topiramate-antipsychotic cotreatment in schizophrenia.
  
  
  
  PubMed/MEDLINE database were searched until September 5, 2015, using the keywords topiramate AND antipsych* OR neurolept* OR specific antipsychotic names.
  
  
  
  Randomized controlled trials (RCTs) of topiramate-antipsychotic cotreatment versus placebo and ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders were included.
  
  
  
  Two evaluators extracted data. Standardized mean difference (SMD), weighted mean difference (WMD), and risk ratio (RR) ± 95% CIs were calculated.
  
  
  
  In 8 RCTs, lasting a mean ± SD of 13.6 ± 4.9 weeks, 439 patients were randomized to topiramate (100-400 mg/d) versus placebo (trials = 7) or ongoing antipsychotic treatment (trial = 1). Topiramate outperformed the comparator regarding total psychopathology (trials = 6, n = 269, SMD = -0.57 [95% CI, -1.01 to -0.14], P = .01), positive symptoms (trials = 4, n = 190, SMD = -0.56 [95% CI, -1.0 to -0.11], P = .01), negative symptoms (trials = 4, n = 190, SMD = -0.62 [95% CI, -1.13 to -0.10], P = .02) general psychopathology (trials = 3, n = 179, SMD = -0.69 [95% CI, -1.27 to -0.11], P = .02), body weight (trials = 7, n = 327, WMD = -3.14 kg [95% CI, -5.55 to -0.73], P = .01), and body mass index (BMI) (trials = 4, n = 198, WMD = -1.80 [95% CI, -2.77 to -0.84], P = .0003). Topiramate's efficacy for total psychopathology and weight reduction effects were not mediated/moderated by trial duration, topiramate dose, sex, age, inpatient status, baseline Positive and Negative Syndrome Scale, or baseline BMI. Conversely, clozapine-topiramate cotreatment moderated greater efficacy, but less weight loss, compared to topiramate-nonclozapine antipsychotic combinations. All-cause discontinuation was similar between topiramate and control groups (trials = 7, RR = 1.24 [95% CI, 0.76 to 2.02], P = .39). Topiramate trended only toward more paresthesia than placebo (trials = 4, RR = 2.03 [95 % CI, 0.99 to 4.18], P = .05).
  
  
  
  Topiramate-antipsychotic cotreatment significantly reduced total, positive, negative, and general psychopathology and weight/BMI in patients with schizophrenia spectrum disorder while being well tolerated. However, larger studies are needed to confirm and extend these findings.
authors.affiliation: Department of Psychiatry, The Zucker Hillside Hospital, 75-59 263rd St, Glen Oaks, NY 11004. ccorrell@lij.edu.|The Zucker Hillside Hospital, Psychiatry Research, North Shore-Long Island Jewish Health System, Glen Oaks, New York bHofstra North Shore-LIJ School of Medicine, Hempstead, New York cThe Feinstein Institute for Medical Research, Manhasset, New York dAlbert Einstein College of Medicine, Bronx, New York eNathan S. Kline Institute for Psychiatric Research, Orangeburg, New York fUniversity Psychiatric Centre KU Leuven, Department of Neurosciences KU Leuven, Leuven, Belgium gDepartment of Community Mental Health, Mental Health Organization North-Holland North, Heerhugowaard, The Netherlands.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
authors.forename: Lawrence
authors.initials: L
authors.lastname: Maayan
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, North Shore-Long Island Jewish Health System, Glen Oaks, New York bHofstra North Shore-LIJ School of Medicine, Hempstead, New York cThe Feinstein Institute for Medical Research, Manhasset, New York dAlbert Einstein College of Medicine, Bronx, New York eNathan S. Kline Institute for Psychiatric Research, Orangeburg, New York fUniversity Psychiatric Centre KU Leuven, Department of Neurosciences KU Leuven, Leuven, Belgium gDepartment of Community Mental Health, Mental Health Organization North-Holland North, Heerhugowaard, The Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: Kane
authors.forename: Marc De
authors.initials: MD
authors.lastname: Hert
authors.forename: Dan
authors.initials: D
authors.lastname: Cohen
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D016017:Odds Ratio; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011594:Psychometrics; D011599:Psychopathology; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D000077236:Topiramate; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D000077236:Topiramate; D005632:Fructose