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Melatonin attenuates antipsychotic metabolic effects: an eight-week randomized, double-blind, parallel-group, placebo-controlled clinical trial

Authors

  • Francisco Romo-Nava,

    1. Departamento de Psiquiatría y Salud Mental, Facultad de Medicina, UNAM, Mexico City, DF, Mexico
    2. Clínica de Trastornos Afectivos, Instituto Nacional de Psiquiatría “Dr. Ramón de la Fuente”, Mexico City, DF, Mexico
    3. Hypothalamic Integration Mechanisms Laboratory, Departmento de Biologia Celular y Fisiologia, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, DF, Mexico
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  • Dení Alvarez-Icaza González,

    1. Clínica de Trastornos Afectivos, Instituto Nacional de Psiquiatría “Dr. Ramón de la Fuente”, Mexico City, DF, Mexico
    2. Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría “Dr. Ramón de la Fuente”, Mexico City, DF, Mexico
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  • Ana Fresán-Orellana,

    1. Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría “Dr. Ramón de la Fuente”, Mexico City, DF, Mexico
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  • Ricardo Saracco Alvarez,

    1. Clínica de Esquizofrenia, Instituto Nacional de Psiquiatría “Dr. Ramón de la Fuente”, Mexico City, DF, Mexico
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  • Claudia Becerra-Palars,

    1. Clínica de Trastornos Afectivos, Instituto Nacional de Psiquiatría “Dr. Ramón de la Fuente”, Mexico City, DF, Mexico
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  • Julia Moreno,

    1. Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría “Dr. Ramón de la Fuente”, Mexico City, DF, Mexico
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  • Martha P Ontiveros Uribe,

    1. Subdirección de Servicios Clínicos, Instituto Nacional de Psiquiatría “Dr. Ramón de la Fuente”, Mexico City, DF, Mexico
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  • Carlos Berlanga,

    1. Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría “Dr. Ramón de la Fuente”, Mexico City, DF, Mexico
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  • Gerhard Heinze,

    1. Departamento de Psiquiatría y Salud Mental, Facultad de Medicina, UNAM, Mexico City, DF, Mexico
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  • Ruud M Buijs

    Corresponding author
    1. Hypothalamic Integration Mechanisms Laboratory, Departmento de Biologia Celular y Fisiologia, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, DF, Mexico
    • Corresponding author:

      Ruud M. Buijs, Ph.D.

      Hypothalamic Integration Mechanisms Laboratory

      Department de Biologia Celular y Fisiologia

      Instituto de Investigaciones Biomédicas

      Ciudad Universitaria

      Universidad Nacional Autónoma de México

      Sede del Tercer Circuito Exterior

      Edificio “B”, 2° Piso

      Mexico City 04510

      Mexico

      Fax: 52 55 56228958

      E-mail: ruudbuijs@gmail.com

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  • ClinicalTrials.gov Identifier: NCT01811160.

Abstract

Objective

Second-generation antipsychotics (SGAs) are among the first-line treatments for bipolar disorder and schizophrenia, but have a tendency to generate metabolic disturbances. These features resemble a metabolic syndrome for which a central autonomic imbalance has been proposed that may originate from the hypothalamic suprachiasmatic nuclei. In a clinical trial, we hypothesized that melatonin, a hormone that regulates the suprachiasmatic nucleus, could attenuate SGA-induced adverse metabolic effects.

Methods

In an eight-week, double-blind, randomized, placebo-controlled, parallel-group clinical trial, we evaluated the metabolic effect of melatonin in SGA-treated patients in terms of weight, blood pressure, lipid, glucose, body composition, and anthropometric measures. A total of 44 patients treated with SGAs, 20 with bipolar disorder and 24 with schizophrenia, randomly received placebo (n = 24) or melatonin 5 mg (n = 20).

Results

The melatonin group showed a decrease in diastolic blood pressure (5.1 versus 1.1 mmHg for placebo, p = 0.003) and attenuated weight gain (1.5 versus 2.2 kg for placebo, F = 4.512, p = 0.040) compared to the placebo group. The strong beneficial metabolic effects of melatonin in comparison to placebo on fat mass (0.2 versus 2.7 kg, respectively, p = 0.032) and diastolic blood pressure (5.7 versus 5.5 mmHg, respectively, p = 0.001) were observed in the bipolar disorder and not in the schizophrenia group. No adverse events were reported.

Conclusions

Our results show that melatonin is effective in attenuating SGAs' adverse metabolic effects, particularly in bipolar disorder. The clinical findings allow us to propose that SGAs may disturb a centrally mediated metabolic balance that causes adverse metabolic effects and that nightly administration of melatonin helps to restore. Melatonin could become a safe and cost-effective therapeutic option to attenuate or prevent SGA metabolic effects.

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