Ziprasidone in the treatment of acute mania: a 12-week, placebo-controlled, haloperidol-referenced study.
This 12-week, double-blind, two-part study in 438 adults with bipolar-associated acute mania began with a 3-week period comparing ziprasidone (80-160 mg/day) and placebo with haloperidol (8-30 mg/day) as active reference. Changes from baseline Mania Rating Scale (MRS) scores for ziprasidone and haloperidol were superior to placebo from day 2 (P = 0.001) to week 3 (P < 0.001); change from baseline at week 3 was greater for haloperidol than ziprasidone (P <or= 0.001). At week 3, the response rate (>or=50% decrease from baseline MRS score) was 36.9, 54.7 and 20.5% for ziprasidone, haloperidol and placebo, respectively (P <or= 0.05, active treatments versus placebo and ziprasidone versus haloperidol). In the 9-week extension phase, ziprasidone replaced placebo to examine tolerability. Maintenance of improvement was evaluated for ziprasidone (40-160 mg/day) or haloperidol (4-30 mg/day). Responses were maintained through the last visit for 88.1% receiving ziprasidone and 96.3% receiving haloperidol. More patients receiving haloperidol than ziprasidone discontinued treatment during weeks 4-12 (21.1% versus 9.6%) and had significantly higher rates of movement disorders. Mean doses of ziprasidone and haloperidol for the first 3-week and 9-week extension were 116.2 mg/day and 121.4 mg/day and 16.0 mg/day and 16.1 mg/day, respectively. Ziprasidone was shown to be effective monotherapy for acute treatment of bipolar mania. Although haloperidol showed greater efficacy, ziprasidone showed a superior tolerability profile.
Vieta
E
E
Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain. evieta@clinic.ub.es
Ramey
T
T
Keller
D
D
English
P A
PA
Loebel
A D
AD
Miceli
J
J
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D015990:Placebo Effect; D011569:Psychiatric Status Rating Scales; D012426:Russia; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone; D006220:Haloperidol