Genetic Polymorphisms and Antipsychotic Medication: Short Term and Long Term Effects

Polymorphisms of various neurotransmitter genes have been shown to be associated with effects and side effects of antipsychotic medications. Most studies have looked at rather short intervals, typically four to six weeks of continuous medication. However, there is a lack of information on effects in the long run and today we do not know whether or not the described effects can be observed only during the first weeks of treatment or have an impact on the outcome after long term therapy as well. Schizophrenic patients were either treated with amisulpride (up to 800mg) or risperidone (up to 8mg) for up to one year. Efficacy was measured by the Positive and Negative Symptom Scale (PANSS). The mean age of the patients was 37 years, the mean duration of illness was eight years, 60% of the patients were male. In accordance with other studies, carriers of the Taq A1 allele of the dopamine receptor DRD2 had a better improvement in PANSS scores after four and six weeks of treatment than the patients who were homozygous for the Taq A2 allele. Several months later, the differences were no longer observed. The results emphasize the importance of the time dimension when studying pharmacogenetic effects. Moreover, mechanisms of initial response might differ from those involved in long term efficacy.