open label study of lithium plus extended-release carbamazepine (erc-cbz) for rapid cycling bipolar disorder

Conditions: Bipolar Disorder

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.

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.

Eligibility 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.