NCT00518947

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Nov 1994

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 1994

Completed
4.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 1999

Completed
8.2 years until next milestone

First Submitted

Initial submission to the registry

August 8, 2007

Completed
13 days until next milestone

First Posted

Study publicly available on registry

August 21, 2007

Completed
Last Updated

February 25, 2011

Status Verified

February 1, 2011

First QC Date

August 8, 2007

Last Update Submit

February 24, 2011

Conditions

Mania

Keywords

Bipolar DisorderManiaAntimanicVerapamilLithium

Outcome Measures

Primary Outcomes (2)

  • 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

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

    3 weeks

Study Arms (3)

1

ACTIVE COMPARATOR

Continued-Lithium

Drug: Lithium

2.

EXPERIMENTAL

Verapamil

Drug: verapamil

3.

EXPERIMENTAL

Verapamil plus Lithium

Drug: verapamil plus lithium

Interventions

LithiumDRUG

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.

1
verapamilDRUG

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.

2.
verapamil plus lithiumDRUG
3.

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (2)

  • 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.

    PMID: 11465518BACKGROUND

  • 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.

    PMID: 19594501RESULT

MeSH Terms

Conditions

ManiaBipolar Disorder

Interventions

LithiumVerapamil

Condition Hierarchy (Ancestors)

Neurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsBipolar and Related DisordersMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Metals, AlkaliElementsInorganic ChemicalsMetals, LightMetalsPhenethylaminesEthylaminesAminesOrganic Chemicals

Study Officials

  • Alan G. Mallinger, M.D.

    University of Pittsburgh

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
FACTORIAL
Sponsor Type
OTHER

Study Record Dates

First Submitted

August 8, 2007

First Posted

August 21, 2007

Study Start

November 1, 1994

Study Completion

June 1, 1999

Last Updated

February 25, 2011

Record last verified: 2011-02

Locations

US(1)