SEIZURES AND MYOCLONUS ASSOCIATED WITH ANTIDEPRESSANT TREATMENT - ASSESSMENT OF POTENTIAL RISK-FACTORS, INCLUDING CYP2D6 AND CYP2C19 POLYMORPHISMS, AND TREATMENT WITH CYP2D6 INHIBITORS

All adverse drug reaction reports labelled seizures or myoclonus durin g treatment with antidepressants and stored in the Swedish national da tabase for spontaneous reporting of adverse drug reactions were review ed in order to evaluate possible risk factors. The reporting physician s were contacted and asked for complementary information, and blood sa mples for determination of the CYP2D6 and CYP2C19 genotypes were obtai ned from patients available. In total, 25 cases of seizures and 7 case s of myoclonus were studied. The drugs included were maprotiline (n=8) , mianserin (n=7), fluvoxamine (n=6), amitriptyline (n=3), clomipramin e (n=3), citalopram (n=2), paroxetine (n=2) and lofepramine (n=1). Pre viously suggested predisposing factors were identified in all but four cases (87%). None of the 11 patients genotyped were found to be poor metabolizers with respect to the enzymes CYP2D6 or CYP2C19. Thus, neit her the CYP2D6 nor the CYP2C19 genotype were found to be associated wi th the occurrence of seizures/myoclonus during treatment with antidepr essants. However, 15 patients (47%) were concomitantly treated with dr ugs with potential inhibitory effects on CYP2D6, such as neuroleptics and dextropropoxyphene, and the patients might thus have been converte d from the extensive metabolizer to the poor metabolizer phenotype dur ing this treatment. Concomitant treatment with drugs decreasing the se izure threshold and/or inhibiting the metabolism of antidepressants ap peared to be an important risk factor for the occurrence of seizures/m yoclonus.