Pharmacotherapy of Treatment-Resistant Mania

Condition(s) targeted: Mania

Intervention: Lithium (Drug); verapamil (Drug); verapamil plus lithium (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: University of Pittsburgh

Official(s) and/or principal investigator(s):
Alan G. Mallinger, M.D., Principal Investigator, Affiliation: University of Pittsburgh

Verapamil has been found in some but not all studies to have antimanic activity. Therefore, we investigated the use of verapamil, alone or as an adjunctive treatment, in manic patients who did not respond to an initial adequate trial of lithium. Each study phase lasted three weeks. Subjects were treated openly with lithium in Phase 1 (n=45). Those who failed to respond were randomly assigned to double-blind treatment in Phase 2 with either verapamil (n=10) or continued lithium (n=8). Phase 2 responders were continued on the same medication in Phase 3. Phase 2 nonresponders (n=10) were assigned to combined verapamil/lithium in Phase 3.

Official title: Pharmacotherapy of Treatment-Resistant Mania

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Factorial Assignment, Safety/Efficacy Study

Primary outcome:

A > 50% reduction in Bech-Rafaelsen Mania Scale score (relative to the baseline score at the start of the phase), and, a total Bech-Rafaelsen Mania Scale score < 11

Very much improved or much improved (compared to baseline) on the Clinical Global Impressions scale

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- To be eligible for the study, patients were required to have a lifetime diagnosis of

bipolar 1 or schizoaffective disorder, a current manic episode meeting DSM-IV criteria, and ratings >/= 7 on the Raskin Severity of Mania Scale and >/= 15 on the Bech-Rafaelsen Mania Scale.

Exclusion Criteria:

Patients were excluded if they had:

- A pattern of severe rapid-cycling in which the patient consistently failed to meet the

duration criteria for discreet episodes of syndromal mania or depression according to DSM-IV

- Sustained drug or alcohol abuse within the past three years

- Schizophrenia

- Organic affective syndrome

- A presenting episode that was secondary to the effect of any pharmacologic agent

- The presence of significant medical illness that would preclude or unduly complicate

the intended pharmacologic management of the episode

- In females, refusal to use appropriate contraception; or

- Pregnancy.

University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States

Related publications:

Frank E, Kupfer DJ, Gerebtzoff A, Meya U, Laghrissi-Thode F, Grochocinski VJ, Houck PR, Mallinger AG, Gibbons RD. The development of study exit criteria for evaluating antimanic compounds. J Clin Psychiatry. 2001 Jun;62(6):421-5.

Starting date: November 1994
Ending date: June 1999
Last updated: August 20, 2007