Pharmacotherapy of Treatment-Resistant Mania - Full Text View

Sponsor:	University of Pittsburgh
Collaborator:	National Institute of Mental Health (NIMH)
Information provided by:	University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00518947

Purpose

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.

Condition	Intervention	Phase
Mania	Drug: Lithium Drug: verapamil Drug: verapamil plus lithium	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Pharmacotherapy of Treatment-Resistant Mania

Resource links provided by NLM:

MedlinePlus related topics: Bipolar Disorder

Drug Information available for: Verapamil Diltiazem hydrochloride Dexverapamil Diltiazem Diltiazem malate Verapamil hydrochloride Lithium carbonate Lithium citrate

U.S. FDA Resources

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:

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 [ Time Frame: 3 weeks ]
Very much improved or much improved (compared to baseline) on the Clinical Global Impressions scale [ Time Frame: 3 weeks ]

Enrollment:	45
Study Start Date:	November 1994
Study Completion Date:	June 1999

Arms	Assigned Interventions
Active Comparator: 1 Continued-Lithium	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.
Experimental: 2. Verapamil	Drug: 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.
Experimental: 3. Verapamil plus Lithium	Drug: verapamil plus lithium

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00518947

Locations

United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

University of Pittsburgh

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:

Alan G. Mallinger, M.D.

University of Pittsburgh

More Information

Publications:

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.

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.

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.

ClinicalTrials.gov Identifier:	NCT00518947 History of Changes
Other Study ID Numbers:	1R01 MH50634
Study First Received:	August 8, 2007
Last Updated:	February 24, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Pittsburgh:

Bipolar Disorder
Mania
Antimanic
Verapamil
Lithium

Additional relevant MeSH terms:

Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Verapamil
Diltiazem
Lithium
Lithium Carbonate
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Arrhythmia Agents

Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Central Nervous System Agents
Psychotropic Drugs
Antimanic Agents
Antidepressive Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012