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Pharmacotherapy of Treatment-Resistant Mania (TRM)

Primary Purpose

Mania

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Lithium
verapamil
verapamil plus lithium
Sponsored by
University of Pittsburgh
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mania focused on measuring Bipolar Disorder, Mania, Antimanic, Verapamil, Lithium

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Pittsburgh

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

1

2.

3.

Arm Description

Continued-Lithium

Verapamil

Verapamil plus Lithium

Outcomes

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

Secondary Outcome Measures

Full Information

First Posted
August 8, 2007
Last Updated
February 24, 2011
Sponsor
University of Pittsburgh
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT00518947
Brief Title
Pharmacotherapy of Treatment-Resistant Mania
Acronym
TRM
Official Title
Pharmacotherapy of Treatment-Resistant Mania
Study Type
Interventional

2. Study Status

Record Verification Date
February 2011
Overall Recruitment Status
Completed
Study Start Date
November 1994 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
June 1999 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Pittsburgh
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mania
Keywords
Bipolar Disorder, Mania, Antimanic, Verapamil, Lithium

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Continued-Lithium
Arm Title
2.
Arm Type
Experimental
Arm Description
Verapamil
Arm Title
3.
Arm Type
Experimental
Arm Description
Verapamil plus Lithium
Intervention Type
Drug
Intervention Name(s)
Lithium
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
verapamil
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
verapamil plus lithium
Primary Outcome Measure Information:
Title
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
Title
Very much improved or much improved (compared to baseline) on the Clinical Global Impressions scale
Time Frame
3 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan G. Mallinger, M.D.
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11465518
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.
Results Reference
background
PubMed Identifier
19594501
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.
Results Reference
result

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Pharmacotherapy of Treatment-Resistant Mania

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