Antipsychotic drug dosage and therapeutic response in schizophrenia is influenced by ABCB1 genotypes: a study from a south Indian perspective.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
Neetha N
NN
Vijayan
Anila
A
Mathew
Shabeesh
S
Balan
Chandrasekhar
C
Natarajan
Chandrashekharan M
CM
Nair
Priya M
PM
Allencherry
Moinak
M
Banerjee
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D054316:Biomarkers, Pharmacological; D016022:Case-Control Studies; D002746:Chlorpromazine / Q000008:administration & dosage; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014150:Antipsychotic Agents; D054316:Biomarkers, Pharmacological; D002746:Chlorpromazine