An efficacy, safety, and dose-response study of Ramelteon in patients with chronic primary insomnia

Pacific Sleep Medicine Services, San Diego, CA 92121, USA.
Sleep Medicine (Impact Factor: 3.15). 02/2006; 7(1):17-24. DOI: 10.1016/j.sleep.2005.09.004
Source: PubMed


To evaluate the efficacy, safety, and dose response of Ramelteon, a novel highly selective MT1/MT2 receptor agonist, in patients with chronic primary insomnia.
A randomized, multicenter, double-blind, placebo-controlled, five-period crossover study design was performed. A total of 107 patients, aged 18-64 years, were randomized into a dosing sequence that included 4, 8, 16, and 32 mg of Ramelteon and placebo. Patients received all five treatments, with a 5- to 12-day washout period between treatments, and served as their own controls. Medication was administered 30 min before habitual bedtime and polysomnographic monitoring. Next-day residual effects were assessed with two visual analog scales (mood and feeling), digit symbol substitution test (DSST), word-list memory tests (immediate recall and delayed recall), and a post-sleep questionnaire that ascertained patients' alertness and ability to concentrate.
All tested doses of Ramelteon resulted in statistically significant reductions in latency to persistent sleep (LPS) and increases in total sleep time (TST). No next-day residual effects were apparent at any dose, as compared with placebo. There were no differences in the number or type of adverse events between any active treatment and placebo group. The most commonly reported adverse events were headache, somnolence, and sore throat.
Ramelteon demonstrated a statistically significant reduction in LPS and a statistically significant increase in TST, with no apparent next-day residual effects, in patients with chronic primary insomnia.

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    • "improved significantly in patients treated with agomelatine compared to those treated with sertraline. This implies that agomelatine normalizes the blunted circadian rhythms of MDD patients [85] [102] [106] more quickly than with the selective serotonin reuptake inhibitor (SSRI). However, there was no 1 to 1 correlation between the RA and depressive symptoms. "
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    ABSTRACT: Major depressive disorder (MDD) is a highly prevalent and disabling disease. Recent studies have highlighted the interactions between the circadian system and depression and indicate a probable bidirectional relationship between MDD and the circadian system. In clinical practice MDD leads to circadian disturbances, and circadian disorders increase the risk of depression. Recent interest has focused on the use of melatonin and melatonin agonists in the treatment and relapse prevention of MDD. This review summarises the mechanisms of the biological clock and its links with MDD. It looks at the effects of melatonin and melatonin agonists on sleep and on symptoms of depression and focuses on agomelatine, a MT1/MT2 agonist and a 5-HT2C antagonist which combines a chronobiotic and antidepressant action with similar efficacy to fluoxetine, venlafaxine and sertraline. Relapse rates are reduced on agomelatine compared to placebo. Agomelatine is well tolerated and rapid improvements in disturbed sleep are reported by patients. In the light of these studies, the potential role of melatonin agonists in treating MDD and subtypes of MDD is discussed.
    Full-text · Article · Aug 2014 · Current Psychiatry Reviews
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    • "Ramelteon is a relatively new drug with high selectivity for the melatonin MT1 and MT2 receptors, which are located in the suprachiasmatic nucleus and have been implicated in the regulation of the sleep-wake cycle. Ramelteon has rapid oral absorption and a short elimination half-life [13] and has negligible affinity for a wide range of other binding sites in the central nervous system (including GABA, benzodiazepine, opioid, muscarinic, histamine, serotonin, and dopamine receptors) [14]. Here, we present three case reports of children with ASD treated with ramelteon. "
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    ABSTRACT: Children with autism spectrum disorders (ASD), including autistic disorder, frequently suffer from comorbid sleep problems. An altered melatonin rhythm is considered to underlie the impairment in sleep onset and maintenance in ASD. We report three cases with autistic disorder in whom nocturnal symptoms improved with ramelteon, a selective melatonin receptor agonist. Insomnia and behavior, assessed using the Clinical Global Impression-Improvement Scale, improved in two cases with 2 mg ramelteon and in the third case with 8 mg ramelteon. Our findings demonstrate that ramelteon is effective not only for insomnia, but for behavioral problems as well, in patients with autistic disorder.
    Full-text · Article · May 2014
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    • "This finding lead to the design of specific agonists ramelteon (Rozerem®, Takeda Pharmaceuticals, Japan) and agomelatine (Valdoxan®, Servier and Novartis). Ramelteon, approved by the FDA (July 2005) for the treatment of insomnia, has been assayed for the treatment of primary insomnia in humans (Erman et al., 2006). Although these studies found it effective and safe, the European Medicines Evaluation Agentcy found the efficacy of ramelteon insufficient for marketing authorization. "

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