Pharmacotherapy of Treatment-Resistant Mania

Study Overview
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Brief Summary
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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.

Official Title
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Pharmacotherapy of Treatment-Resistant Mania

Conditions
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Mania

Intervention / Treatment
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* Drug: Lithium
* Drug: verapamil
* Drug: verapamil plus lithium


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Continued-Lithium | Drug: Lithium<br>* 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.<br>|
| Experimental: 2.<br>Verapamil | Drug: verapamil<br>* 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.<br>|
| Experimental: 3.<br>Verapamil plus Lithium | Drug: verapamil plus lithium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar Disorder, Mania, Antimanic, Verapamil, Lithium