Antidepressant Response Linked to Norepinephrine Transporter Genotype

Peter ForsterBest Practices, Major Depression, Testing, Treatments of Depression

A large study of patients treated with venlafaxine found that antidepressant response was linked to the norepinephrine transporter (NET) genotype. The study looked at response in a sample of 350 individuals over the age of 60 with severe depression (MADRS greater than or equal to 15) who were treated with venlafaxine up to a dose of 300 mg a day. It found a significant effect size for norepinephrine transporter type (which explained 25% of the variance in outcomes).

“After adjusting for multiple comparisons, NET variant rs2242446 (T-182C) was significantly associated with remission (odds ratio=1.66, 95% CI=1.13, 2.42). Individuals with the rs2242446 C/C genotype were more likely to remit (73.1%) than those with either the C/T (51.8%) or the T/T genotype (47.3%). Individuals with the C/C genotype also had a shorter time to remission than those with the C/T or T/T genotypes and had a greater percentage change in MADRS score from baseline to end of treatment (up to week 12).”

The authors note that two smaller studies of younger adults have been conducted. One found an association of NET genotype with treatment response and the other did not.

Unfortunately, the norepinephrine transporter is not included in the two genetic test panels that we have been using: Genesight and Genecept.

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Norepinephrine Transporter Gene Variants and Remission From Depression With Venlafaxine Treatment in Older AdultsVictoria S. Marshe, Malgorzata Maciukiewicz, Soham Rej, Arun K. Tiwari, Etienne Sibille, Daniel M. Blumberger, Jordan F. Karp, Eric J. Lenze, Charles F. Reynolds III, James L. Kennedy, Benoit H. Mulsant, and Daniel J. Müller. American Journal of Psychiatry 0 0:0. 2017