Ramelteon for the Treatment of Insomnia and Mood Stability in Patients With Euthymic Bipolar Disorder

Study Overview
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Brief Summary
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The purpose of this study is to determine whether treating sleep difficulties in patients with bipolar disorder also improves their mood stability.

Detailed Description
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Patients with euthymic bipolar disorder, although free of significant mood symptoms, often have continued sleep disturbances. Improving patients' sleep by also normalizing the circadian rhythm will lead to fewer mood exacerbations. Ramelteon offers a new and more pharmacologically exact mechanism to re-synchronize the SCN. The administration of ramelteon for bipolar patients will improve sleep and will cause fewer mood exacerbations. Patients with bipolar disorder often experience frequent mood alterations that are attempted to be controlled by mood stabilizing agents and anti-psychotic agents. Both classes of medications have numerous significant side effects. Establishing that ramelteon is helpful in the sleep of patients with bipolar disorder and helpful in mood stability will increase the number of treatment options for bipolar patients.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled Trial of Ramelteon for the Treatment of Insomnia and Mood Stability in Patients With Euthymic Bipolar Disorder.

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Ramelteon
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent before initiation of any study-related procedures Men and women aged 18 to 65 years. A documented clinical diagnosis according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) meeting criteria 296.4x Bipolar I disorder, most recent episode manic, 296.6x Bipolar I disorder, most recent episode mixed, or 296.5x Bipolar I disorder, most recent episode depressed. PSQI total score of >=5. MADRS total score of <=12. YMRS total score of <= 12 Female patients of childbearing potential must have a negative urine pregnancy test at enrollment and be willing to use a reliable method of birth control, i.e., double-barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device or tubal ligation, during the study. Be able to understand and comply with the requirements of the study, as judged by the investigator. Outpatient status at enrollment. Exclusion Criteria: Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the patient's current psychiatric status. Presence of prohibited medications of antidepressants (including MAOI's) and systemic corticosteroids. Patients with a diagnosis of primary insomnia disorders Patients with a diagnosis of severe chronic obstructive pulmonary disease A clinical finding that is untreated (eg, hypertension, poorly controlled diabetes, angina) or that, in the opinion of the investigator, would be negatively affected by the study medication or that would affect the study medication. Patients with active substance abuse diagnoses (except tobacco abuse). Known history of intolerance or hypersensitivity to ramelteon or to any other component in the tablet.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ramelteon<br>8 mg | Drug: Ramelteon<br>* one 8 mg tablet at bedtime for up to 6 months<br>* Other names: Rozerem;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* one tablet at bedtime for up to 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pittsburgh Sleep Quality Index (PSQI) Global Score | Self-rated scale to measure quality of sleep via questions regarding sleep latency, duration, efficiency, disturbances, use of sleep medication, and daytime dysfunction. Scores range from 0-21, higher scores represent more significant sleep disturbance. | Monthly for 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | 10-item, standardized, well-validated scale used to measure severity of depressive symptoms; sensitive to treatment effects in depressed outpatients. Scores range from 0-60, higher scores represent more severe depressive symptoms. | Monthly for 6 months | 
| Young Mania Rating Scale (YMRS) Total Score | 11-item standardized, well-validated scale used to measure manic symptoms; sensitive to treatment effects in manic patients. Scores range from 0-60, higher scores represent more severe manic symptoms. | Monthly for 6 months | 
| Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score | 3-part (mania, depression, overall bipolar illness), physician-administered scale used to assess global illness severity; used to measure change. Each part is rated from 1-7, higher scores represent more severe mental illness. Only overall bipolar rating was used. | Monthly for 6 months | 
| Cumulative Proportion of Participants in Each Arm Surviving Without Relapse | Survival analysis techniques, including Kaplan Meier curves, were used to evaluate group differences in time to relapse. Relapse was defined as a medication initiation or change for manic/depressed/mixed symptoms, a hospitalization for manic/depressed/mixed symptoms, MADRS score >= 16, YMRS score > 14, and suicide risk or imminent risk of suicide. Time to relapse was measured discretely in terms of the number of assessment visits until discontinued from the study. | Monthly for 6 months |