Pharmacodynamic Genetic Variants Related to Antipsychotic Adverse Reactions in Healthy Volunteers

Abstract

Aim: Clinical trials with healthy volunteers are a useful model for evaluating safety and tolerability, without the interference of concomitant diseases and drugs. The present study aims to improve our understanding of antipsychotic-related adverse reactions (ARs) and their possible association with common genetic variants of pharmacodynamic proteins such as neurotransmitter receptors/transporters. Materials & methods: A total of eight polymorphisms located in seven pharmacodynamic-related genes (SCL6A4, MDR1, 5HT2A, DRD2, DRD3, COMT and GRIN2B) were genotyped in a cohort of 211 healthy volunteers who received a single dose of risperidone (1 mg), olanzapine (5 mg) or quetiapine (25 mg). Results: Interestingly, a significant association was found between the incidence of neurological ARs and specific polymorphisms in key genes (DRD2 and SCL6A4). Conclusion: Genetic variants in pharmacodynamic genes could represent valuable markers of AR risk and antipsychotic safety.

Original submitted 7 February 2013; Revision submitted 3 June 2013

KEYWORDS::

• adverse reaction
• genetic marker
• olanzapine
• quetiapine
• risperidone

Acknowledgements

This study would not have been possible without the cooperation of the healthy volunteers. Editorial assistance was kindly provided by Fundación de Investigación Biomédica del Hospital Universitario de La Princesa (T O‘Boyle).

Financial & competing interests disclosure

The study was supported by Fondo de Investigaciones Sanitarias (FIS-EC07/90466) of Instituto de Salud Carlos III, Madrid, Spain and by Fundación Teófilo Hernando, a nonprofit foundation linked to Universidad Autónoma de Madrid. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No funded writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The study was supported by Fondo de Investigaciones Sanitarias (FIS-EC07/90466) of Instituto de Salud Carlos III, Madrid, Spain and by Fundación Teófilo Hernando, a nonprofit foundation linked to Universidad Autónoma de Madrid. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No funded writing assistance was utilized in the production of this manuscript.