Pharmacotherapy of Treatment-Resistant Mania

Mania Clinical Trial

— TRM  

Official title:

Pharmacotherapy of Treatment-Resistant Mania

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00518947
• Other study ID #: 1R01MH050634
• Status: Completed
• Phase: Phase 3
• First received: August 8, 2007
• Last updated: February 24, 2011
• Start date: November 1994
• Est. completion date: June 1999

Study information

• Verified date: February 2011
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: June 1999
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mania

Intervention

Drug:
• Lithium
Treatment with lithium carbonate was initiated at a dose of 900-1200 mg/day. Serum lithium levels were monitored twice weekly, and the dose was adjusted to attain target levels between 0.8 and 1.0 mmol/L by the end of week one, with subsequent levels as high as 1.4 mmol/L permitted if needed.
• verapamil
The initial dose of verapamil was 80 mg b.i.d., and this was raised by 80 mg/day every three days to a maximum of 480 mg/day, unless intolerable side effects were produced at a lower level, in which case the dose was maintained at the highest tolerated amount.
• verapamil plus lithium

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pittsburgh	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (3)

A.G. Mallinger, M.E. Thase, R. Haskett, J. Buttenfield, D.A. Luckenbaugh, E. Frank, D.J. Kupfer, H.K. Manji: Verapamil Plus Lithium: A Potential Treatment For Mania Unresponsive To Lithium Alone. Bipolar Disorders 9 (Suppl 1), 72, 2007.

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. — View 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 mecha — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		3 weeks
Primary	Very much improved or much improved (compared to baseline) on the Clinical Global Impressions scale		3 weeks