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.