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Pharmacotherapy of Treatment-Resistant Mania (TRM)

This study has been completed.
National Institute of Mental Health (NIMH)
Information provided by:
University of Pittsburgh Identifier:
First received: August 8, 2007
Last updated: February 24, 2011
Last verified: February 2011
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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pharmacotherapy of Treatment-Resistant Mania

Resource links provided by NLM:

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
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.
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


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
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Please refer to this study by its identifier: NCT00518947

United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
National Institute of Mental Health (NIMH)
Principal Investigator: Alan G. Mallinger, M.D. University of Pittsburgh
  More Information

Publications: Identifier: NCT00518947     History of Changes
Other Study ID Numbers: 1R01MH050634 ( U.S. NIH Grant/Contract )
Study First Received: August 8, 2007
Last Updated: February 24, 2011

Keywords provided by University of Pittsburgh:
Bipolar Disorder

Additional relevant MeSH terms:
Bipolar Disorder
Bipolar and Related Disorders
Mental Disorders
Lithium Carbonate
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Vasodilator Agents processed this record on August 16, 2017