Clinical trial NCT00518947: Pharmacotherapy of Treatment-Resistant Mania
Official title: Pharmacotherapy of Treatment-Resistant Mania
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mania
Keywords: Bipolar Disorder
Mania
Antimanic
Verapamil
Lithium
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2007-08-21
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: 3 weeks
measure: Very much improved or much improved (compared to baseline) on the Clinical Global Impressions scale
timeFrame: 3 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Alan G. Mallinger, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.4088/jcp.v62n0604.
citation: Mallinger AG, Thase ME, Haskett R, Buttenfield J, Luckenbaugh DA, Frank E, Kupfer DJ, Manji HK. Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone: preliminary findings and a discussion of therapeutic mechanisms. Bipolar Disord. 2008 Dec;10(8):856-66. doi: 10.1111/j.1399-5618.2008.00636.x.