The pharmacogenetics of antipsychotic-induced adverse events.
OBJECTIVE
Antipsychotic drugs are effective in alleviating a variety of symptoms and are medication of first choice in schizophrenia. However, a substantial interindividual variability in side effects often requires a lengthy 'trial-and-error' approach until the right medication is found for the right patient. Genetic factors have long been hypothesized to be involved and identification of related gene variants could be used to predict and tailor drug treatment.


RESULTS
This review highlighting the most recent genetic findings was conducted on the two most common and most well-studied side effects: antipsychotic-induced weight gain and tardive dyskinesia.


CONCLUSIONS
Regarding weight gain, most promising and most consistent findings were obtained in the serotonergic system (HTR2C) and with hypothalamic leptin-melanocortin genes, in particular with one variant close to the melanocortin-4-receptor (MC4R) gene. With respect to tardive dyskinesia, most interesting findings were generally obtained in genes related to the dopaminergic system (dopamine receptors D2 and D3), and more recently with glutamatergic system genes. Overall, genetic studies have been successful in identifying strong findings, in particular for antipsychotic-induced weight gain and to some extent for tardive dyskinesia. Apart from the need for replication studies in larger and well-characterized samples, the next challenge will be to create predictive algorithms that can be used for clinical practice.
Pharmacogenetics Research Clinic, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. daniel.mueller@camh.ca
Daniel J
DJ
Müller
Nabilah I
NI
Chowdhury
Clement C
CC
Zai
D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000235:genetics*; D009069:Movement Disorders / Q000209:etiology*; D020641:Polymorphism, Single Nucleotide; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents