Placebo-Controlled Pilot Study of Ramelteon for Adiposity and Lipids in Patients With Schizophrenia

Schizophrenia Program, Massachusetts General Hospital, Boston, MA, USA.
Journal of clinical psychopharmacology (Impact Factor: 3.24). 08/2011; 31(5):653-8. DOI: 10.1097/JCP.0b013e31822bb573
Source: PubMed

ABSTRACT Few interventions have been successful to prevent or reverse the medical complications associated with antipsychotic agents in the schizophrenia population. In particular, no single agent can correct multiple metabolic abnormalities such as insulin resistance, hyperlipidemia, inflammation, obesity, and fat distribution. We now report a randomized placebo-controlled pilot study to examine the effects of ramelteon on obesity and metabolic disturbances among subjects with schizophrenia.
A double-blind, placebo-controlled, 8-week pilot trial was conducted, adding ramelteon 8 mg/d to stable outpatients with schizophrenia. Vital signs and anthropometric measurements, including height, weight, waist circumference, and body fat were assessed, and laboratory assays were tracked to monitor changes in metabolic markers.
Twenty-five subjects were randomly assigned to treatment with study drug or placebo, and 20 subjects were included in the final analysis. Ramelteon did not improve anthropometric measurements, glucose metabolism, and inflammatory markers. There was, however, a significant decrease in total cholesterol and ratio of cholesterol to high-density lipoprotein in the ramelteon group. Although the standard anthropometric measures did not show significant change, the dual-energy x-ray absorptiometry scan showed a trend toward reduction in fat in the abdominal and trunk areas with a moderate effect size.
Although ramelteon decreased cholesterol, treatment may have to be longer than 8 weeks and with a higher dose for maximal effect of ramelteon for body fat and lipid changes. Future studies are needed for patients with schizophrenia with a larger sample size to fully understand ramelteon's effects on abdominal adiposity and lipids.

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    • "In contrast, patients with WC values above the cutoff showed normal levels of FFM. These findings may be explained, on the one hand, by the fact that the use of atypical antipsychotics (which is very frequent in these patients) is strongly associated to abdominal adiposity (Borba et al., 2011), and, on the other hand, by the agerelated loss of FFM. "
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    • "reduced olanzapine-induced weight gain and visceral adiposity (Raskind et al., 2007). Results of a small randomized study have shown that ramelteon (a melatonin receptor agonist) could significantly attenuate hyperlipidemia associated with AAPs intake (Borba et al., 2011). "
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    ABSTRACT: Unlabelled: We aimed to determine the efficacy of melatonin 3 mg/day in prevention of olanzapine-induced metabolic side-effects. In a randomized double-blind placebo-controlled study, 48 patients with first-episode schizophrenia who were eligible for olanzapine treatment, were randomly assigned to olanzapine plus either melatonin 3 mg/day or matched placebo for eight weeks. Anthropometric and metabolic parameters as well as psychiatric symptoms using The Positive and Negative Syndrome Scale (PANSS) were assessed at baseline, week 4, and 8. Primary outcome measure was the change from baseline in weight at week 8. Data were analyzed using t-test, Mann-Whitney U test, and mixed-effects model. Thirty-six patients had at least one post-baseline measurement. At week eight, melatonin was associated with significantly less weight gain [mean difference (MD) = 3.2 kg, P = 0.023], increase in waist circumference [MD = 2.83 cm, P = 0.041] and triglyceride concentration [MD = 62 mg/dl, P = 0.090 (nearly significant)] than the placebo. Changes in cholesterol, insulin, and blood sugar concentrations did not differ significantly between the two groups. Patients in the melatonin group experienced significantly more reduction in their PANSS scores [MD = 12.9 points, P = 0.014] than the placebo group. No serious adverse events were reported. To summarize, in patients treated with olanzapine, short-term melatonin treatment attenuates weight gain, abdominal obesity, and hypertriglyceridemia. It might also provide additional benefit for treatment of psychosis. The study was registered in the ( Registration number: NCT01593774).
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    • "It is a selective agonist for MT 1 /MT 2 receptors without significant affinity for other receptor sites (Miyamoto, 2009). Because there is increasing information on the involvement of melatonin and MT 1 /MT 2 receptors in the regulation of several aspects of the metabolic syndrome (Cardinali et al., 2011) a recent study tested whether ramelteon is effective to reverse the multiple metabolic abnormalities associated with antipsychotic agents in the schizophrenia population such as insulin resistance, hyperlipidemia, inflammation, obesity, and fat distribution (Borba et al., 2011). A double-blind, placebo-controlled, 8-week pilot trial was conducted, adding ramelteon 8 mg/day to 45 stable outpatients with schizophrenia. "
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