RELATIONSHIP BETWEEN PLASMA DESIPRAMINE LEVELS, CYP2D6 PHENOTYPE AND CLINICAL-RESPONSE TO DESIPRAMINE - A PROSPECTIVE-STUDY

Objective: The clinical relevance of the CYP2D6 oxidation polymorphism in the treatment of depression with desipramine (DMI) was studied pro spectively in depressed outpatients. Methods: After CYP2D6 phenotype d etermination with dextromethorphan, 31 patients were treated with oral DMI at a dosage of 100 mg per day for 3 weeks. At the end of the 3rd week of treatment, severity of depressive symptoms was assessed by the Hamilton Depression Rating Scale and steady-state plasma concentratio ns of DMI and its metabolite 2-hydroxydesipramine (2-OH-DMI) were meas ured by high-performance liquid chromatography (HPLC). Results: Plasma DMI levels were significantly correlated with dextromethorphan metabo lic ratio. The two patients with the poor metabolizer phenotype showed the highest plasma concentrations of DMI and complained of severe adv erse effects, requiring dosage reduction. No significant correlation w as found between plasma levels of either DMI or DMI plus 2-OH-DMI and anti depressant effect. Conclusion: These findings indicate that the d extromethorphan metabolic ratio has a great impact on steady-state pla sma levels of DMI in depressed patients and may identify subjects at r isk for severe concentration-dependent adverse effects. On the other h and, this index of CYP2D6 activity does not seem to predict the degree of clinical amelioration.