A randomized, placebo-controlled study of adjunctive ramelteon in ambulatory bipolar I disorder with manic symptoms and sleep disturbance

Abstract

This study evaluated the efficacy and tolerability of ramelteon in ambulatory bipolar I disorder with manic symptoms and insomnia. Twenty-one outpatients with bipolar I disorder by Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria with mild-to-moderate manic symptoms and sleep disturbance were randomized to receive either ramelteon (N=10) or placebo (N=11) in an 8-week, double-blind, fixed-dose (8 mg/day) study. Ramelteon and placebo had similar rates of reduction in ratings of symptoms of insomnia, mania, and global severity of illness. However, ramelteon was associated with improvement in a global rating of depressive symptoms. It was also well tolerated and associated with no serious adverse events. The small sample size may have limited the ability of the study to detect potentially clinically important drug-placebo differences. Further studies of ramelteon in subgroups of bipolar patients with sleep disturbance, including those with depression or euthymia, seem indicated.

An Update on the Use of Sedative-Hypnotic Medications in Psychiatric Disorders

“…In this study, ramelteon did not demonstrate efficacy greater than placebo on the primary outcome measure (change in insomnia assessed by 65-item Pittsburgh Insomnia Rating Scale), nor did it have differential effects on manic symptoms or global severity of illness (23). However, it did demonstrate improvement in global rating of depressive symptoms, and no serious adverse events were observed (23). Although this study represents one of the first attempts to conduct a randomized controlled study for insomnia in bipolar disorder, the small sample size (total N=21), as well as the fact that patients were hypomanic, may limit the power of the study to detect benefit over placebo, as well as the generalizability of results to the management of comorbid insomnia in other phases of bipolar disorder.…”

“…McElroy and colleagues assessed the use of ramelteon 8mg nightly versus placebo in outpatients with bipolar disorder experiencing mild to moderate manic symptoms and insomnia (23). During the course of the 8-week study, other medications were continued and left unchanged (except in instances in which a medication required dose reduction for side effect management) (23).…”

“…During the course of the 8-week study, other medications were continued and left unchanged (except in instances in which a medication required dose reduction for side effect management) (23). In this study, ramelteon did not demonstrate efficacy greater than placebo on the primary outcome measure (change in insomnia assessed by 65-item Pittsburgh Insomnia Rating Scale), nor did it have differential effects on manic symptoms or global severity of illness (23). However, it did demonstrate improvement in global rating of depressive symptoms, and no serious adverse events were observed (23).…”

Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on pharmacopsychiatry

“…A small pilot study suggested that adding valnoctamide 600-1,200 mg/day (which is an anticonvulsant analogue of valproate that does not undergo biotransformation to the corresponding free acid and in mice has been shown to be distinctly less teratogenic than valproate) on risperidone was more efficacious against acute mania in comparison with risperidone plus placebo [62]. A pilot study on the usefulness of adjunctive ramelteon against acute mania/mixed was positive [340].…”

Insomnia Comorbid to Severe Psychiatric Illness

“…Two small clinical trials have recently evaluated ramelteon for sleep disturbance in bipolar disorder. One study evaluated the efficacy and tolerability of ramelteon in BD type I with manic symptoms and insomnia (53). Twenty-one outpatients were randomized to receive either 8mg/day of ramelteon (N=10) or placebo (N=11) in an 8-week double-blind treatment design.…”