Open Label Study of Lithium Plus Extended-Release Carbamazepine (ERC-CBZ) for Rapid Cycling Bipolar Disorder
Study Details
Study Description
Brief Summary
This is an open label design using Lithium plus extended release carbamazepine (Equetro) in combination for 6 months. Rapid cycling bipolar disorder is frequently treatment refractory and associated with repeated hospitalizations and complications. The results of this study will offer a promising approach to treat this complex disorder. The primary efficacy measure will be the time to relapse. Relapse will determined by the investigator based on the following: Need for additional pharmacotherapy for mood-related symptoms, hospitalization for an mood episode, increase of more than 50% in HAM-D and YMRS scores from the baseline visit.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Open label Design with Lithium plus Extended release carbamazepine combination for 6 months. Extended release carbamazepine at doses of 1600 mg/day will be utilized. Lithium dosage will be adjusted to maintain therapeutic blood levels.
Patient Population: N = 20.
Primary and Secondary Efficacy Endpoints:
The primary efficacy measure will be the time to relapse. Relapse will determined by the investigator based on the following
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Need for additional pharmacotherapy for affective symptoms
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Hospitalization for an affective episode
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Increase of more than 50% in HAM-D and YMRS scores from baseline
The differences in the frequency of affective episodes in the 6-month prior to the treatment with ERC-CBZ and 6 months after treatment initiation will also be measured. Secondary efficacy measures will include; changes in the 17- Item Hamilton Depression Scale (HAM-D), Young Mania Rating Scale (YMRS), Clinical Global Severity Scale (CGI -S), Clinical Global Improvement Scale (CGI-I) scores at baseline and scores during treatment with ERC-CBZ.
Inclusion Criteria:
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Subjects, 19 years and older with DSM-IV defined Bipolar Disorder with a history of the rapid cycling within the past 12 months.
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Subjects may be either in a manic, mixed or depressive phase at time of study entry.
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Subjects must be on lithium therapy for 6 months or longer. Stable lithium therapy will be defined as: No changes in lithium dosage for at least 2 weeks prior to study entry and a therapeutic lithium level (0.6 to 1.2 mEq) prior to study entry.
Exclusion Criteria:
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Subjects with a lifetime history of Schizophrenia or Schizoaffective Disorder
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If patients are on thyroid replacement therapy they have to on stable doses for the past 3 months at study enrollment.
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Presence of active suicide ideations or score of > 3 on the suicide subscale of the 17 - item HAM-D.
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Current substance dependence (excluding nicotine) defined as no dependence criteria for 30 days prior to study enrollment
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Subjects with a history of non-response to carbamazepine or lithium
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Subjects who are pregnant or planning to become pregnant
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Subjects with a history of allergic/idiosyncratic reaction or intolerability to carbamazepine or lithium.
Study Procedures:
Preliminary Phase: The Structured Clinical Interview Diagnostic Schedule (SCID), medical & psychiatric history and baseline laboratory testing, EKG; pregnancy test will be obtained to ensure study eligibility. Eligible subjects will receive ERC-CBZ at starting doses ranging from 100 to 200 mg b.i.d. depending on clinical presentation and further titration up to a maximum dose of 1600 mg/day will be done at the discretion of the investigator. This titration phase will not extend beyond 2 weeks during which changes in concomitant medications will be allowed. Next, all psychotropics excluding lithium, ERC-CBZ and benzodiazepines will be tapered over a 2-week period. During the preliminary phase subjects will be seen weekly and assessments will be made using the HAM-D, YMRS, CGI -S, CGI-I, AE, and Concomitant medications
Open Label Phase: Subjects on lithium and ERC-CBZ therapy will enter this phase for 6 months. Changes to both lithium and ERC-CBZ will be permitted during this phase with serum levels to guide titration. Use of lorazepam, as a rescue medication will be permitted. Study visits will be every biweekly for 6 months. The HAM-D, YMRS and CGI-S, CGI-I, AE, concomitant medications will be assessed at each visit. Compliance will be assessed by pill counts at each study visit.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 Treatment with lithium and extended release carbamazepine |
Drug: Lithium Plus Extended- Release Carbamazepine
Preliminary phase subjects receive ERC-CBZ starting dose range from 100 to 200 mg b.i.d. and further titration up to a maximum dose of 1600 mg/day done at the discretion of the investigator. Titration phase will not extend beyond 2 weeks.Open label phase subjects stabilized on lithium and ERC-CBZ therapy will enter this phase for 6 months
Other Names:
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Outcome Measures
Primary Outcome Measures
- The primary efficacy measure will be the time to relapse. Relapse will determined by; need for additional pharmacotherapy, hospitalization for an affective episode, increase of >/= 50% in HAM-D and YMRS scores. [Patients will be seen weekly during preliminary phase and biweekly during the open label phase]
Secondary Outcome Measures
- The differences in the frequency of affective episodes in the 6-month prior to the treatment with ERC-CBZ and 6 months after treatment initiation will also be measured. Secondary efficacy measures will include; changes in the 17- Item Hamilton Depression [Patients will be seen weekly during the preliminary phase and biweekly during the open label phase]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subjects, 19 years and older with DSM-IV defined Bipolar Disorder with a history of the rapid cycling within the past 12 months.
-
Subjects may be either in a manic, mixed or depressive phase at time of study entry.
-
Subjects must be on lithium therapy for 6 months or longer. Stable lithium therapy will be defined as: No changes in lithium dosage for at least 2 weeks prior to study entry and a therapeutic lithium level (0.6 to 1.2 mEq) prior to study entry.
Exclusion Criteria:
-
Subjects with a lifetime history of Schizophrenia or Schizoaffective Disorder
-
If patients are on thyroid replacement therapy they have to on stable doses for the past 3 months at study enrollment.
-
Presence of active suicide ideations or score of > 3 on the suicide subscale of the 17
- item HAM-D.
-
Current substance dependence (excluding nicotine) defined as no dependence criteria for 30 days prior to study enrollment
-
Subjects with a history of non-response to carbamazepine or lithium
-
Subjects who are pregnant or planning to become pregnant
-
Subjects with a history of allergic/idiosyncratic reaction or intolerability to carbamazepine or lithium.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Creighton University Department of Psychiatry | Omaha | Nebraska | United States | 68131 |
Sponsors and Collaborators
- Creighton University
- Shire
Investigators
- Principal Investigator: Sriram Ramaswamy, M.D., Creighton University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 05-13934