[Extrapyramidal side effects of neuroleptic and antidepressant treatment: assessment of potential risk factors through CYP2D6 genetic polymorphism].
The objective of this study was to assign metabolizer phenotype (cytochrome P450 2D6 or CYP2D6) to drug treated psychiatric adult patients to assess if the CYP2D6 polymorphism could be a potential risk factor for the development of extrapyramidal side effects of psychotropic drugs. Twenty-eight unrelated in-patients (16 men and 12 women) treated with antidepressants and/or antipsychotic drug were phenotyped using dextromethorphan. Two groups of patients were considered depending on the presence (n = 14) or not (n = 14) of extrapyramidal side effects. The mean dextromethorphan/dextrorphan metabolic ratio (log10) did not differ between the two groups of patients (-1.13 +/- 0.9 and -1.56 +/- 0.5, NS). But significantly more patients with extrapyramidal side effects (n = 4) than patients without side effects (n = 0) were poor metabolizers. This result could be due to a quantitative difference between the 2 groups of drug treatment cosegregated with dextromethorphan, but several authors reported that extrapyramidal side effects seemed not to be always related to high plasma drug levels. So the authors concluded that the 2D6 polymorphism could be a risk factor of poor neurologic tolerance of psychotropic drugs, but not only through pharmacokinetic consequences. CYP 2D6 is indeed expressed in brain and seems to interfer with the metabolism of dopamine and other related neurotransmitters.
Reggiani
K
K
Service de Psychiatrie, Centre Hospitalier Spécialisé, Novillars.
Vandel
P
P
Haffen
E
E
Sechter
D
D
Bizouard
P
P
Vandel
S
S
D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001480:Basal Ganglia Diseases / Q000139:chemically induced*; D001921:Brain / Q000502:physiology*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6
Effets indésirables extrapyramidaux des neuroleptiques et antidépresseurs--recherche de facteurs de risque: rôle du polymorphisme génétique du CYP2D6.