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Neurocognitive performance, subjective well-being, and psychosocial functioning after benzodiazepine withdrawal in patients with schizophrenia or bipolar disorder: a randomized clinical trial of add-on melatonin versus placebo

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European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Chronic benzodiazepine use is common in patients with mental illness and is associated with cognitive impairment. It is unclear whether benzodiazepine-induced cognitive impairment is reversible. Amelioration of cognitive dysfunction may be facilitated during benzodiazepine tapering by add-on melatonin due to its anti-inflammatory and neuroprotective properties. We examined how melatonin and benzodiazepine withdrawal affect cognition, subjective well-being, and psychosocial functioning. Eighty patients with schizophrenia or bipolar disorder were randomized to add-on treatment once daily with either prolonged-release melatonin or placebo in a 24-week, double-blind clinical trial. All participants gradually tapered usual benzodiazepine dosage in a closely monitored treatment setting. We used the Brief Assessment of Cognition in Schizophrenia (BACS) to assess neurocognitive performance with additional assessments of subjective well-being and psychosocial functioning. BACS composite and subscale scores (except motor speed) significantly improved in parallel with benzodiazepine dose reduction, but there was no additional effect of melatonin. Cognitive performance was still markedly impaired post-tapering compared with normative data. Neither benzodiazepine withdrawal nor treatment group affected subjective well-being or psychosocial functioning. In conclusion, add-on melatonin does not seem to affect cognition, well-being, or psychosocial functioning in patients with severe mental illness. The observed improvement in cognitive performance could not be distinguished from retest effects, which may in turn have been facilitated by the benzodiazepine tapering.

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Acknowledgments

The trial was funded by the Research Fund of the Mental Health Services of the Capital Region of Denmark via a postdoc grant and a grant for external randomization and database management. Further funding was obtained from Axel Thomsen and Martha Thomsen’s Foundation. The Lundbeck Foundation Center of Clinical Intervention and Neuropsychiatric Schizophrenia Research covered residual expenses. The funding bodies had no role in trial design or in the collection, analysis, and interpretation of data.

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Authors and Affiliations

  1. Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Copenhagen University Hospital, Mental Health Center Glostrup, Mental Health Services - Capital Region of Denmark, Glostrup, Denmark

    Lone Baandrup, Birgitte Fagerlund & Birte Glenthoj

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  1. Lone Baandrup
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  2. Birgitte Fagerlund
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  3. Birte Glenthoj
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Correspondence to Lone Baandrup.

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The authors declare that they have no conflict of interest.

Ethical standards

This trial was approved by the Committee on Biomedical Research Ethics of The Capital Region in Denmark (H-1-2011-025), the Danish Medicines Agency (EudraCT 2010-024065-46), and the Danish Data Protection Agency (RHP-2011-07: 01217) and was registered at ClinicalTrials.gov (NCT01431092). The authors confirm that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All participants provided written informed consent.

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Baandrup, L., Fagerlund, B. & Glenthoj, B. Neurocognitive performance, subjective well-being, and psychosocial functioning after benzodiazepine withdrawal in patients with schizophrenia or bipolar disorder: a randomized clinical trial of add-on melatonin versus placebo. Eur Arch Psychiatry Clin Neurosci 267, 163–171 (2017). https://doi.org/10.1007/s00406-016-0711-8

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  • DOI: https://doi.org/10.1007/s00406-016-0711-8

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