Antidepressants genetic polymorphism

Masimirembwa, C. M. Hasler, J. A. (1997). Genetic polymorphism of drug metabolising enzymes in African populations implications for the use of neuroleptics and antidepressants. Brain. Res. Bull., 44(5), 561-71. 

Individuals with the short form of the serotonin transporter have a poorer response to lithium (55). The short form of the serotonin transporter is a genetic polymorphism that increases the risk of depression in the setting of adversity (56,57,58) and reduces the likelihood of a response to antidepressant treatment, and is therefore associated with a poorer outcome (59,60,61,62). Similarly, a single nucleotide polymorphism (SNP) in the gene that encodes brain-derived neurotrophic factor (the val66met SNP of BDNF) has been associated with a poor response to lithium (63). This SNP is over-represented among patients with rapid cycling (64), who are less likely to respond well to lithium. 

Drugs that are metabolized by the cytochrome P-450 (CYP) isoenzymes CYP2D6, CYP2C9, and CYP2C19 also exhibit genetic polymorphisms. An example of CYP2D6 metabolism is debrisoquine. In about 5-10 /o of Caucasians in North America and Europe and about 1% of Asians, 4-hydroxylation of debrisoquine is reduced, and such individuals are at increased risk for toxicity (orthostatic hypotension). Beta blockers (metoprolol and timolol), antiarrhythmic drugs (encainide and flecainide), tricyclic antidepressants... 

Smeraldi, E., Zanardi, R. et al. (1998). Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Mol. Psychiatry, 3(6), 508-11. Wang, S. L., Huang, J. D. et al. (1993). Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects polymorphism in RFLP and DNA sequence of CYP2D6. Clin. Pharmacol. Ther., 53(4), 410-18. 

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