Ramelteon as an Adjunct Therapy in Non-Diabetic Patients With Schizophrenia

This is an 8-week randomized, double blind, placebo-controlled pilot study with 4- week follow up assessment, of ramelteon 8 mg/day, administered to subjects for 8 consecutive weeks as an adjunctive therapy in 40 non-diabetic schizophrenia subjects to examine ramelteon effects on body composition, glucose and lipid metabolism, sleep quality and symptoms of tardive dyskinesia using the Massachusetts General Hospital General Clinical Research Center. As far as we know, no previous study has been done to explore the potential role of ramelteon in improving metabolic, sleep, and movement disturbances in schizophrenia subjects. The novel approach of adjunctive ramelteon treatment in the schizophrenia population is promising.

Inclusion criteria

• diagnosis of schizophrenia, schizoaffective disorder, any subtype or schizophreniform disorder
• male or female, age 18-65 years
• treatment with clozapine, olanzapine, quetiapine or risperidone
• well established compliance with medications
• Body Mass Index (BMI) of > 27 Kg/m² with any component of metabolic syndrome or insulin resistance or a BMI of > 30 Kg/m²:

Exclusion criteria

• inability to provide informed consent
• substance and alcohol abuse
• significant medical illness, including congestive heart failure, severe hepatic impairment, severe Chronic Obstructive Pulmonary Disease (COPD), severe sleep apnea, severe cardiovascular disease or renal disease
• current history of diabetes mellitus or thyroid disease
• women who are pregnant, breastfeeding, or who are unwilling or unable to use an effective form of birth control during the entire study
• psychiatrically unstable, patients with major depression
• patients treated with medications known to affect glucose tolerance such as birth control pills containing norgestrel, steroids, beta blockers, anti-inflammatory drugs (including daily aspirin and ibuprofen), thiazide diuretics; and agents that induce weight loss will be excluded from the study
• treatment with fluvoxamine in the or ketoconazole past two weeks
• treatment with fluconazole (a strong CYP2C9 inhibitor).
• subjects treated with ziprasidone and aripiprazole conventional agents
• treatment with sedative-hypnotics such as barbiturates, zolpidem, eszopiclone, zaleplon. The use of stable daily doses of benzodiazepines is allowed.
• known hypersensitivity to ramelteon or any of its components