The influence of acetylator phenotype on the outcome of treatment with phenelzine, in a clinical trial.

It has been suggested that the rate of metabolism of phenelzine is dependent on the acetylator phenotype of the recipient and, therefore, that acetylator phenotype may be an indicator of clinical importanc e. Acetylator phenotype was determined in a group of patients suffering from depressive, anxiety or phobic neurosis. These patients were blindly allocated to treatment with phenelzine or placebo, in addition to diazepam. Ratings of clinical state were made at weekly intervals. A principle component analysis of the improvement scores on all the clinical rating scales was used to provide a slight measure of improvement for each patient. Increases in severity of undesirable symptoms or spontaneous complaints were taken to indicate side effects. Assessments of whole blood MAO and 5-HT, and urinary 5-HIAA and VMA were made before treatment and at weekly intervals during the course of treatment. Data from improvement scores indicate that there is a treatment effect only in the first 2 weeks and there is no significant difference between fast and slow acetylators. For the dropouts, the ratio of slow to fast acetylators is not significantly different from that in the total group. MAO is inhibited by phenelzine and the degree of inhibition is independent of acetylator phenotype. Changes of whole blood 5-HT concentration during the course of treatment are complex and suggest that there is an interaction between treatment and acetylator phenotype. The results suggest that fast acetylation is associated with an increased metabolism of 5-HT. It is concluded that acetylator phenotype should not be regarded as a prognostic indication of clinical importance and that the rate of acetylation is not directly related to the appearance or disappearance of monoamine oxidase inhibition by phenelzine.