title: Risk for adverse events and discontinuation due to adverse events of ziprasidone monotherapy relative to placebo in the acute treatment of bipolar depression, mania, and schizophrenia.
abstract: OBJECTIVE
  This study aimed to examine the risk difference (RD) in the discontinuation due to adverse events, akathisia, overall extrapyramidal symptoms (EPS), reported-somnolence, and 7% or greater weight gain between ziprasidone monotherapy and placebo in the acute treatment of bipolar depression (BPD), bipolar mania (BPM), and schizophrenia.
  
  
  METHODS
  Pooled data from 9 randomized, double-blind, placebo-controlled, acute studies of ziprasidone in BPD, BPM, and schizophrenia were used. The number needed to treat to harm (NNTH) of ziprasidone relative to placebo was estimated when an RD was statistically significant.
  
  
  RESULTS
  The RD in discontinuation due to adverse events or 7% or greater weight gain between ziprasidone and placebo was not significant in all 3 psychiatric conditions. The risk for akathisia with ziprasidone was significantly higher in BPD with an RD of 2.3% (NNTH = 44) and in BPM with an RD of 8.4% (NNTH = 12). Risk for overall EPS with ziprasidone was significantly higher in BPM with an RD of 8.7% (NNTH = 12) and schizophrenia with an RD of 3.3% (NNTH = 30). Risk of reported-somnolence with ziprasidone was also significantly higher in BPD with an RD of 11.8% (NNTH = 8), BPM with an RD of 14.3% (NNTH = 7), and schizophrenia with an RD of 7% (NNTH = 14). Dose-dependent increase in the risk for reported somnolence with ziprasidone was observed in BPD and schizophrenia.
  
  
  CONCLUSIONS
  Ziprasidone was associated with significant differential adverse effects relative to placebo in BPM, BPD, and schizophrenia with no significant difference in weight gain in all 3 groups. Self-reported somnolence was increased across the 3 conditions. Subjects with BPM were more vulnerable to EPS than those with BPD or schizophrenia.
authors.affiliation: Mood and Anxiety Clinic in the Mood Disorders Program of the Department of Psychiatry, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA. keming.gao@uhhospitals.org
authors.forename: Keming
authors.initials: K
authors.lastname: Gao
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pappadopulos
authors.forename: Onur N
authors.initials: ON
authors.lastname: Karayal
authors.forename: Sheela
authors.initials: S
authors.lastname: Kolluri
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy; D012894:Sleep Stages / Q000187:drug effects; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone