Antipsychotic Drug Dosage and Therapeutic Response in Schizophrenia is Influenced by ABCB1 Genotypes: A Study from a South Indian Perspective

Abstract

Aim: The conventional practice of using trial and error mode to select antipsychotic drugs in treatment of schizophrenia can result in symptom exacerbations, relapse and severe side effects, resulting in higher costs of treatment. P-glycoprotein (ABCB1) is known to regulate the concentration of antipsychotic drugs in the brain. Variable expressivity based on polymorphism in the gene ABCB1 may reflect on the drug response and its relationship to dosage. Materials & methods: All antipsychotic dosages administered to patients were converted to common chlorpromazine equivalents. Response to antipsychotics was based on 50% cutoff in Brief Psychiatric Rating Scale ratings after 1-year of follow-up. Using a case–control study design, ABCB1 polymorphisms were screened in 192 individuals grouped into responders and nonresponders. Results: A strong allelic, genotypic and haplotypic association, was observed, which was predictive of good response to antipsychotics. Individuals carrying the favorable homozygous genotypes of rs1045642 and rs2032582 displayed better response with increased dosage while those carrying risk genotype manifested refractoriness on increased dosage. Conclusion: The study suggests that a priori knowledge of ABCB1 genotypes can provide a significant input into evaluating the patient‘s response to medication, and minimizing redundant dosing and refractoriness.

Original submitted 14 February 2012; Revision submitted 14 May 2012

KEYWORDS::

• ABCB1
• antipsychotics
• BPRS rating
• chlorpromazine
• dosing
• pharmacogenomics
• polytherapy
• refractory
• schizophrenia
• south India

Financial & competing interests disclosure

NN Vijayan receives financial support as Junior Research Fellow from University Grants Commission, Government of India. 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 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

NN Vijayan receives financial support as Junior Research Fellow from University Grants Commission, Government of India. 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 writing assistance was utilized in the production of this manuscript.