Ziprasidone in the treatment of acute mania: a 12-week, placebo-controlled, haloperidol-referenced study

• Published in: Journal of psychopharmacology (Oxford) Vol. 24; no. 4; pp. 547 - 558
• Main Authors: Vieta, E., Ramey, T., Keller, D., English, PA, Loebel, AD, Miceli, J.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-04-2010; Sage Publications; Sage Publications Ltd
• Subjects: Adult; Adult and adolescent clinical studies; Adults; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Biological and medical sciences; Bipolar disorder; Bipolar Disorder - diagnosis; Bipolar Disorder - drug therapy; Bipolar Disorder - psychology; Comparative analysis; Depression; Double-Blind Method; Drugs; Female; Haloperidol - adverse effects; Haloperidol - therapeutic use; Humans; India; Male; Mania; Medical sciences; Middle Aged; Mood disorders; Neuropharmacology; Patient Dropouts; Pharmacology. Drug treatments; Piperazines - adverse effects; Piperazines - therapeutic use; Placebo Effect; Psychiatric Status Rating Scales; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Russia; Thiazoles - adverse effects; Thiazoles - therapeutic use; Time Factors; Treatment Outcome; United States; Young Adult; United States; India; Russia; haloperidol; bipolar; depression; ziprasidone; mania; Mood disorder; Atypical antipsychotic; Neuroleptic; Psychotropic; Ziprasidone; Dopamine antagonist; Acute; Depression; Butyrophenone derivatives; Haloperidol; 5-HT2 Serotonine receptor; D2 Dopamine receptor; Treatment; Placebo; Mania; Piperazine derivatives
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881108099418

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 ≤ 0.001). At week 3, the response rate (≥50% decrease from baseline MRS score) was 36.9, 54.7 and 20.5% for ziprasidone, haloperidol and placebo, respectively (P ≤ 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.