title: The efficacy and safety of switching to ziprasidone from olanzapine in patients with bipolar I disorder: an 8-week, multicenter, open-label study.
abstract: BACKGROUND
  Switching antipsychotic medication in patients undergoing combination therapy for bipolar I disorder is a common clinical practice because of suboptimal drug efficacy or tolerability. Despite the frequency of switching, little is known about the most appropriate switching options. Ziprasidone may be a good alternative for patients with bipolar disorder experiencing a suboptimal response or intolerance to olanzapine in combination with a mood stabilizer because of its mood-stabilizing effect and minimal propensity for clinically significant body weight gain and metabolic disturbances. However, no study has evaluated the efficacy, safety, and tolerability of switching to ziprasidone from olanzapine in combination with a mood stabilizer for treatment of bipolar disorder.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the efficacy and safety of switching to ziprasidone in patients with bipolar I disorder experiencing a suboptimal response or intolerance to olanzapine in combination with lithium or valproate.
  
  
  METHODS
  An 8-week, prospective, open-label study was conducted among inpatients and outpatients with bipolar I disorder who were taking olanzapine combined with lithium or valproate to treat recent manic or mixed episodes. In subjects experiencing a suboptimal response [≥16 points on the Young Mania Rating Scale (YMRS) at screening and baseline] or intolerance, olanzapine was switched to ziprasidone while maintaining the same dose of their current combined mood stabilizer during the 8-week trial. The primary efficacy measure was the mean change in the YMRS total score. Metabolic parameters were measured to evaluate the improvement in metabolic syndrome.
  
  
  RESULTS
  A total of 56 patients were enrolled, and 46 (82.1 %) completed this study. Switching to ziprasidone was effective and well-tolerated. YMRS total scores were significantly reduced over 8 weeks (mean change, -10.4 ± 10.2). There were significant improvements in metabolic parameters, with mean changes of -0.4 ± 0.8 kg/m(2) in body mass index (BMI), -1.2 ± 2.5 kg in body weight, -21.3 ± 62.7 mg/dL in the fasting triglyceride level, and -13.2 ± 26.6 mg/dL in the total cholesterol level. Greater improvements in BMI, body weight, and dyslipidemia were positively correlated with a higher baseline BMI and abnormal lipid profile.
  
  
  CONCLUSIONS
  Ziprasidone appears to be a good switching option for patients with bipolar I disorder experiencing suboptimal response or intolerance with olanzapine in combination with lithium or valproate. In addition, switching to ziprasidone improves metabolic parameters, especially in patients experiencing weight gain or dyslipidemia with olanzapine treatment.
authors.affiliation: Department of Psychiatry, Mood Disorders Clinic, Seoul National Hospital, 398, Neungdong-ro, Gwangin-gu, Seoul, 143-711, Republic of Korea, HwangbinLee@gmail.com.
authors.forename: Hwang-Bin
authors.initials: HB
authors.lastname: Lee
authors.forename: Bo-Hyun
authors.initials: BH
authors.lastname: Yoon
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Kwon
authors.forename: Young Sup
authors.initials: YS
authors.lastname: Woo
authors.forename: Jung-Goo
authors.initials: JG
authors.lastname: Lee
authors.forename: Moon-Doo
authors.initials: MD
authors.lastname: Kim
authors.forename: Won-Myong
authors.initials: WM
authors.lastname: Bahk
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D057915:Drug Substitution / Q000379:methods*; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000139:chemically induced / Q000175:diagnosis; D005260:Female; D006801:Humans; D008094:Lithium / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; D014635:Valproic Acid; C092292:ziprasidone; D008094:Lithium; D000077152:Olanzapine