Polymorphisms of the DRD2 , ANKK1 , DAT1 , DBH , and DRD4 genes have been found to moderate the effects of pharmacotherapy  of alcohol , opioid , and cocaine use disorders .
The integration of genetic information with clinical data will inform health professionals of the most efficacious pharmacotherapeutic intervention for substance use disorders .
Substance use disorders have significant personal , familial , and societal consequences .
Despite the serious consequences of substance use , only a few therapies are effective in treating substance use disorders , thus highlighting a need for improved treatment practice s. Substance use treatment response depends on multiple factors such as genetic , biological , and social factors .
It is essential that each component is represented in treatment plans .
The dopaminergic system plays a critical role in the pharmacotherapy for addictions , and an underst and ing of the role of variation of genes involved in this system is essential for its success .
Pharmacogenetics of antidepressant medication intolerance.
OBJECTIVE The authors sought to identify genetic markers for antidepressant medication intolerance . Genetic variation in drug metabolizing enzymes such as cytochrome P450 2D6 ( CYP2D6 ) has been postulated to underlie antidepressant intolerance ( pharmacokinetic effect ) . However , variation in genes encoding serotonin receptors could also explain antidepressant side effects ( pharmacodynamic effect ) . METHOD An 8-week , double-blind , r and omized pharmacogenetic study compared the widely prescribed antidepressants paroxetine ( a selective serotonin reuptake inhibitor [ SSRI ] ) and mirtazapine ( not an SSRI ) in 246 elderly patients with major depression . Genotypes were determined for the 102 T/C single nucleotide polymorphism ( SNP ) in the serotonin 2A ( 5-HT(2A ) ) locus ( HTR2A ) , previously associated with psychotropic medication treatment outcome . Oligonucleotide microarrays were used to extensively characterize variation in the CYP2D6 gene . Clinical outcomes included treatment discontinuations , adverse events , medication compliance , and change in mood . RESULTS Survival analysis showed discontinuations due to paroxetine-induced side effects were strongly associated with the HTR2A C/C genotype . There was a significant linear relationship between the number of C alleles and the probability of discontinuation . Side effect severity in paroxetine-treated patients with the C/C genotype was also greater . In contrast , HTR2A 102 T/C genotype had no effect on mirtazapine side effects . CYP2D6 genotype did not predict treatment outcome for either medication . CONCLUSIONS Pharmacodynamic differences among patients due to variant 5-HT(2A ) receptors appear to be more important than pharmacokinetic variation in determining paroxetine intolerance . Pharmacogenetic markers may be useful in predicting antidepressant treatment outcome
Polymorphisms of the DRD2 , ANKK1 , DAT1 , DBH , and DRD4 genes have been found to moderate the effects of pharmacotherapy  of alcohol , opioid , and cocaine use disorders .
The integration of genetic information with clinical data will inform health professionals of the most efficacious pharmacotherapeutic intervention for substance use disorders .
Substance use disorders have significant personal , familial , and societal consequences .
Despite the serious consequences of substance use , only a few therapies are effective in treating substance use disorders , thus highlighting a need for improved treatment practice s. Substance use treatment response depends on multiple factors such as genetic , biological , and social factors .
It is essential that each component is represented in treatment plans .
The dopaminergic system plays a critical role in the pharmacotherapy for addictions , and an underst and ing of the role of variation of genes involved in this system is essential for its success .