title: A randomized, double-blind, placebo-controlled study of ziprasidone monotherapy in bipolar disorder with co-occurring lifetime panic or generalized anxiety disorder.
abstract: OBJECTIVE
  Bipolar disorder often co-occurs with anxiety disorders. Evidence suggests that second-generation antipsychotics (SGAs) may be useful in treating both conditions. This study examined the efficacy of ziprasidone in the treatment of these disorders.
  
  
  METHODS
  This 3-site, randomized, double-blind, placebo-controlled, parallel group, 8-week trial of ziprasidone monotherapy examined 49 subjects with bipolar disorder and lifetime panic disorder (with or without agoraphobia) or generalized anxiety disorder (GAD) experiencing moderately severe anxiety symptoms at entrance into the study. Both bipolar disorder and anxiety diagnoses were based on DSM-IV-TR criteria. Patients were screened and randomized from June 25, 2010, through August 23, 2011. Primary outcome measures were the Clinical Global Impressions-21 Anxiety Scale (CGI-21 Anxiety) and the Sheehan Disability Scale (SDS), with secondary measures monitoring anxiety and mood symptoms.
  
  
  RESULTS
  Last-observation-carried-forward analyses demonstrated that patients in the ziprasidone group did not improve significantly more than those in the placebo group on the CGI-21 Anxiety (F1 = 0.34; P = .564) or SDS (F1 = 0.26; P = .611). Secondary analysis using hierarchical linear modeling found similar results (CGI-21 Anxiety: F1 = 1.82; P = .178; and SDS: F1 = 0.70; P = .408). Regardless of group, time in the study was associated with significant decrease in anxiety (F1 = 11.08; P = .001) and total disability (F1 = 26.16; P < .001). Patients in the ziprasidone group showed a greater increase in abnormal involuntary movement, and 81.8% (n = 9) of the subjects who withdrew from the study due to adverse events, serious adverse events, or side effects were in the ziprasidone group.
  
  
  CONCLUSIONS
  Results suggest that ziprasidone monotherapy was not associated with a clinically significant improvement in anxiety symptoms or improved function for patients with bipolar disorder, lifetime panic disorder or GAD, and concurrent moderately severe anxiety symptoms, and it was associated with a more negative side-effect profile relative to placebo.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01172652.
authors.affiliation: VA Palo Alto Health Care System, 3801 Miranda Ave (151T), Palo Alto, CA 94304 tsuppes@stanford.edu.
authors.forename: Trisha
authors.initials: T
authors.lastname: Suppes
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.forename: David V
authors.initials: DV
authors.lastname: Sheehan
authors.forename: Rosario B
authors.initials: RB
authors.lastname: Hidalgo
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Cosgrove
authors.forename: Iola S
authors.initials: IS
authors.lastname: Gwizdowski
authors.forename: Natalie S
authors.initials: NS
authors.lastname: Feldman
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000453:epidemiology; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000453:epidemiology; D015897:Comorbidity; D004311:Double-Blind Method; D006801:Humans; D008875:Middle Aged; D016584:Panic Disorder / Q000188:drug therapy / Q000453:epidemiology; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D010919:Placebos; D013844:Thiazoles; C092292:ziprasidone