TY - JOUR
T1 - Genetic dissection of drug effects in clinical practice
T2 - CLOCK gene and clozapine-induced diurnal sleepiness
AU - Lattuada, Enrico
AU - Cavallaro, Roberto
AU - Benedetti, Francesco
AU - Cocchi, Federica
AU - Lorenzi, Cristina
AU - Smeraldi, Enrico
PY - 2004/9/2
Y1 - 2004/9/2
N2 - 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.
AB - 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.
KW - Circadian rhythms
KW - CLOCK gene
KW - Clozapine
KW - Genetic polymorphisms
KW - Schizophrenia
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U2 - 10.1016/j.neulet.2004.05.084
DO - 10.1016/j.neulet.2004.05.084
M3 - Article
C2 - 15331141
AN - SCOPUS:4344594151
VL - 367
SP - 152
EP - 155
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 2
ER -