A pharmacogenetic intervention for the improvement of the safety profile of antipsychotic treatments

Abstract

Antipsychotic drugs fail to achieve adequate response in 30–50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG−, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG−), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG− patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG− clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes.