Genetic dissection of drug effects in clinical practice: CLOCK gene and clozapine-induced diurnal sleepiness

Enrico Lattuada, Roberto Cavallaro, Francesco Benedetti, Federica Cocchi, Cristina Lorenzi, Enrico Smeraldi

Research output: Contribution to journalArticlepeer-review

Abstract

Psychotic patients treated with clozapine often experience persistent daytime sleepiness. This is a frequent side effect of clozapine that may reduce patient compliance. We hypothesized that clozapine might interfere with the circadian rhythms regulated by the biological clock. In 171 patients with major psychosis, we investigated the association between hypersomnolence during clozapine therapy and a CLOCK gene polymorphism (3111 T/C substitution). Forty-six patients showed persistent daytime sleepiness and were classified as "sleepy". "Sleepy" patients were significantly more likely to have a mutated allele compared to both "non sleepy" patients and healthy subjects (χ 2 = 20.36, d.f. = 1, P = 0.000007, and χ 2 = 13.91, d.f. = 1, P = 0.0002, respectively). We conclude that an interaction between clozapine and the CLOCK gene polymorphism 3111 T/C substitution could explain persistent daytime sleepiness in a significant proportion of patients treated with clozapine.

Original languageEnglish
Pages (from-to)152-155
Number of pages4
JournalNeuroscience Letters
Volume367
Issue number2
DOIs
Publication statusPublished - Sep 2 2004

Keywords

  • Circadian rhythms
  • CLOCK gene
  • Clozapine
  • Genetic polymorphisms
  • Schizophrenia

ASJC Scopus subject areas

  • Neuroscience(all)

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