Open Label Study of Lithium Plus Extended-Release Carbamazepine (ERC-CBZ) for Rapid Cycling Bipolar Disorder

Condition(s) targeted: Bipolar Disorder

Intervention: Lithium Plus Extended- Release Carbamazepine (Drug)

Phase: Phase 4

Status: Active, not recruiting

Sponsored by: Creighton University

Official(s) and/or principal investigator(s):
Sriram Ramaswamy, M.D., Principal Investigator, Affiliation: Creighton University

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.

Official title: Open Label Prophylaxis Study of Lithium Plus Extended- Release Carbamazepine (Equetro®) Combination for Rapid Cycling Bipolar Disorder

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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.

Secondary outcome: 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

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

- Need for additional pharmacotherapy for affective symptoms

- Hospitalization for an affective episode

- 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: 1. Subjects, 19 years and older with DSM-IV defined Bipolar Disorder with a history of the rapid cycling within the past 12 months. 2. Subjects may be either in a manic, mixed or depressive phase at time of study entry. 3. 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: 1. Subjects with a lifetime history of Schizophrenia or Schizoaffective Disorder 2. If patients are on thyroid replacement therapy they have to on stable doses for the past 3 months at study enrollment. 3. Presence of active suicide ideations or score of > 3 on the suicide subscale of the 17

- item HAM-D.

4. Current substance dependence (excluding nicotine) defined as no dependence criteria for 30 days prior to study enrollment 5. Subjects with a history of non-response to carbamazepine or lithium 6. Subjects who are pregnant or planning to become pregnant 7. 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.

Minimum age: 19 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Subjects, 19 years and older with DSM-IV defined Bipolar Disorder with a history of the rapid cycling within the past 12 months. 2. Subjects may be either in a manic, mixed or depressive phase at time of study entry. 3. 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: 1. Subjects with a lifetime history of Schizophrenia or Schizoaffective Disorder 2. If patients are on thyroid replacement therapy they have to on stable doses for the past 3 months at study enrollment. 3. Presence of active suicide ideations or score of > 3 on the suicide subscale of the

17 - item HAM-D.

4. Current substance dependence (excluding nicotine) defined as no dependence criteria for 30 days prior to study enrollment 5. Subjects with a history of non-response to carbamazepine or lithium 6. Subjects who are pregnant or planning to become pregnant 7. Subjects with a history of allergic/idiosyncratic reaction or intolerability to carbamazepine or lithium.

Creighton University Department of Psychiatry, Omaha, Nebraska 68131, United States

Starting date: May 2006
Last updated: December 13, 2007