Genetics and Health

Serotonin Transporter and Norepinephrine Transporter Genes Determine Effectiveness of Antidepressants

by Hsien Hsien Lei, PhD on October 4th, 2006

A study of 241 Korean patients with major depression has identified polymorphisms in the in the serotonin transporter (5-HTT) and norepinephrine transporter (NET) genes which influence a person’s response to antidepressants, including selective serotonin reuptake inhibitor (SSRI) and norepinephrine reuptake inhibitor (NRI).

• In white populations, depressed patients with the long allele 5-HTTLPR genotypes (sl and ll) generally show a greater response to SSRIs than those with a short allele genotype (ss).
• Korean patients who responded to Aventyl were nearly eight times more likely to carry the NET G1287A polymorphism (odds ratio, 7.54, 95% confidence interval, 2.53-22.49, P<0.001).
• Patients who responded to an SSRI were twenty times more likely to carry the 5-HTT intron 2 s/l variation. (odds ratio 20.11, 95% CI, 4.27- 94.74, P<0.001).
• Patients who responded to an SSRI were three times more likely to carry the s/l variants in the 5-HTT promoter region (odds ratio, 3.34, 95% CI, 1.41-7.91, P=0.006).
• The favorable allele for SSRI response was S 5-HTTLPR, which contrasts with findings of the influence of polymorphisms on antidepressant responses in white patients.
• The S 5-HTTLPR was associated also with a response to Aventyl (odds ratio, 3.73, 95% CI, 1.32-10.53; P=0.01)
• The NET G1287A GG genotype, which occurs in 56% of the population in Korea, was associated with better response to Aventyl than to either Prozac or Zoloft. (83.3% to 58.7%, odds ratio 3.52, 95% CI, 1.39-8.95; P=0.006).

For most people, choosing an antidepressant without genetic information is still very much hit or miss. The authors of this JAMA study state that initial drug treatments fail in 30% to 40% of patients with major depression. The Mayo Clinic has more on how to select the antidepressant that’s right for you.

Once you and your doctor have selected an antidepressant for you to try, it may take four to eight weeks to determine its full effectiveness. With some medications, you can take the full dosage immediately. With others, you may need to gradually increase your dose.

If you have no improvement at all in your symptoms after six weeks, it may be time to try a different antidepressant or add a second medication to augment your treatment. You may have to taper off of one medication before starting another, because potentially dangerous drug interactions and withdrawal-like symptoms can occur from an abrupt switch.

NB: You may also be interested in the Carnival of Depression, Bipolar Disorder, and Mental Health Journeys.

JAMA, October 4, 2006
MedPage Today, October 3, 2006

Technorati Tags: depression, major depression, serotonin, norepinephrine, ssri, nri, prozac, aventyl, genetics, genes, dna, diseases, illness, health, mental health, mental illness

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