A double-blind, randomized, placebo-controlled trial of adjunctive ramelteon for the treatment of insomnia and mood stability in patients with euthymic bipolar disorder

Fapm, Edward R Norris, Md, Fapa,; Burke, Karen M.; Correll, Julia; Zemanek, Kenneth J.; Lerman, Joel A.; Primelo, Ralph A; Kaufmann, Michael W.

doi:10.1016/j.jad.2012.06.023

Cited by 68 publications

(44 citation statements)

References 24 publications

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“…There is exciting preliminary evidence that treating sleep or circadian disturbance with ramelteon can reduce the risk of manic and depressive relapse, supporting the idea that treating sleep can improve the course of illness (54). A recent report has provided exciting preliminary evidence of the efficacy and safety of CBT-I in BD (60).…”

Section: Bipolar Disorder (Bd)mentioning

confidence: 93%

“…While ramelteon did not significantly differ from placebo in reducing symptoms of insomnia, mania, and global severity of illness, it was tolerable and associated with improvement in a global rating of depressive symptoms. Another recent study of ramelteon focused on treating sleep disturbance in euthymic BD patients (54). Participants were randomized to receive ramelteon (n=42) or placebo (n=41) for up to 24 weeks.…”

Section: Bipolar Disorder (Bd)mentioning

confidence: 99%

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Insomnia Comorbid to Severe Psychiatric Illness

Soehner

Kaplan

Harvey

2013

Sleep Medicine Clinics

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In psychiatric illness, there is a growing body of evidence indicating that sleep disturbances exert a detrimental influence on the course of these disorders and contribute to impaired function. Even when psychiatric disorders are successfully treated or stabilized, insomnia and other sleep disturbances often fail to remit. The present review focuses on sleep in two severe mental illnesses, namely bipolar disorder and schizophrenia. This article discusses the role of sleep disturbances and altered sleep architecture in relation to symptom status, functional impairment, quality of life, and the course of these disorders. Current evidence regarding pharmacological and psychological treatment approaches for insomnia in these populations is presented. This review also notes considerations for adapting Cognitive Behavioral Therapy for insomnia (CBT-I) procedures for severe mental illness and proposes directions for future research.

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Section: Bipolar Disorder (Bd)mentioning

confidence: 93%

Section: Bipolar Disorder (Bd)mentioning

confidence: 99%

Insomnia Comorbid to Severe Psychiatric Illness

Soehner

Kaplan

Harvey

2013

Sleep Medicine Clinics

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“…One study found that in BD patients with euthymia and sleep disturbances, ramelteon adjunctive to mood stabilizers (8 mg/day, 23 weeks double-blind, n = 83) effectively maintained mood stabilization. Notably, the group taking ramelteon had half the relapse rate of those treated with placebo (Norris et al, 2013). …”

Section: Therapeutic Targets For Rapid Antidepressant Efficacy Beymentioning

confidence: 99%

New targets for rapid antidepressant action

Machado‐Vieira

Henter

Zarate

2017

Progress in Neurobiology

127

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Current therapeutic options for major depressive disorder (MDD) and bipolar disorder (BD) are associated with a lag of onset that can prolong distress and impairment for patients, and their antidepressant efficacy is often limited. All currently approved antidepressant medications for MDD act primarily through monoaminergic mechanisms. Glutamate is the major excitatory neurotransmitter in the central nervous system, and glutamate and its cognate receptors are implicated in the pathophysiology of MDD, and in the development of novel therapeutics for this disorder. The rapid and robust antidepressant effects of the N-methyl-D-aspartate (NMDA) antagonist ketamine were first observed in 2000. Since then, other NMDA receptor antagonists have been studied in MDD. Most have demonstrated relatively modest antidepressant effects compared to ketamine, but some have shown more favorable characteristics. This article reviews the clinical evidence supporting the use of novel glutamate receptor modulators with direct affinity for cognate receptors: 1) non-competitive NMDA receptor antagonists (ketamine, memantine, dextromethorphan, AZD6765); 2) subunit (GluN2B)-specific NMDA receptor antagonists (CP-101,606/traxoprodil, MK-0657); 3) NMDA receptor glycine-site partial agonists (GLYX-13); and 4) metabotropic glutamate receptor (mGluR) modulators (AZD2066, RO4917523/basimglurant). We also briefly discuss several other theoretical glutamate receptor targets with preclinical antidepressant-like efficacy that have yet to be studied clinically; these include α-amino-3-hydroxyl-5-methyl-4-isoxazoleproprionic acid (AMPA) agonists and mGluR2/3 negative allosteric modulators. The review also discusses other promising, non-glutamatergic targets for potential rapid antidepressant effects, including the cholinergic system (scopolamine), the opioid system (ALKS-5461), corticotropin releasing factor (CRF) receptor antagonists (CP-316,311), and others.

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“…[13] Studies on the therapeutic benefit of modulating circadian rhythms in both preclinical models (CK01, inhibitor of the casein kinase 1 (CK1) ε/δ, which is believed to be involved in the modulation of the molecular clock) and clinical trials (ramelteon, agonist of melatonergic MT1 and MT2 receptors) have yielded encouraging results. [12,14] Other novel drugs targeting intra-and extracellular pathways involved in the pathogenesis of BD are currently investigated in ongoing clinical trials. [12] The amino-acid taurine exhibited an ability to change depressionrelated signaling cascades in preclinical studies and probably prevents glutamate-induced neuronal excitotoxicity.…”

Section: Current Limitations and Future Perspectives In Drug Developmmentioning

confidence: 99%

Challenges with bipolar disorder drug discovery

Konstantakopoulos

2016

Expert Opinion on Drug Discovery

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A double-blind, randomized, placebo-controlled trial of adjunctive ramelteon for the treatment of insomnia and mood stability in patients with euthymic bipolar disorder

Cited by 68 publications

References 24 publications

Insomnia Comorbid to Severe Psychiatric Illness

Insomnia Comorbid to Severe Psychiatric Illness

New targets for rapid antidepressant action

Challenges with bipolar disorder drug discovery

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