Aim: to assess whether pharmacogenetic polymorphisms are associated with increased adverse effects or non-response with certain antidepressants whose metabolism is highly dependent on specific CYP450 isoenzymes. This is interim analysis of an ongoing study
We used a Case Control design comparing patients with major depressive disorder or generalized anxiety disorder who had had increased adverse effects from specified antidepressants (Cases) to patients who were poor responders to an antidepressant but without significant adverse effects (Controls) Genecept Assay™ (battery of pharmacogenetic tests relevant to psychiatry) was obtained using saliva or cheek swab
Importantly, 57.1% of Cases were poor or intermediate metabolizers on the concerned isoenzyme vs. 17.2% of Controls (p= .006) 52.9% of subjects who had at least one severe adverse effect were found to be poor or intermediate metabolizers on the concerned isoenzyme compared to 24.2% of those who did not. This difference showed a trend towards statistical significance (p= .061) 69.2% of subjects who had more than one severe adverse effect were found to be poor or intermediate metabolizers on the concerned isoenzyme compared to 21.6% of those who did not (p= .005) 27.6% of Controls were ultrarapid metabolizers on the concerned isoenzyme vs. 14.3% of Cases (p= .221) No statistically significant differences in the proportions of Cases vs. Controls who were homozygous (TT) for methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, or for the Short/Short form of the serotonin transporter promoter region allele.
Patients on certain commonly used antidepressants who had increased adverse effects were very likely to be poor or intermediate metabolizers on the relevant CYP450 isoenzyme Pharmacogenetic testing should routinely be considered in these patients
Mago, Rajnish; Gupta, S.; Huhn, Kelly; and Shah, R., "Genetic Polymorphisms and Antidepressant Adverse Effects" (2015). Department of Psychiatry and Human Behavior Faculty Papers. Paper 24.