The presence of specific genetic variations may determine whether selective serotonin reuptake inhibitors and norepinephrine reuptake inhibitors are effective for patients with late-life major depression, according to an article in the October 4 issue of the Journal of the American Medical Association.

Initial drug treatments fail in 30 percent to 40 percent of patients with major depression. Pharmacogenetic prediction of response is one possibility for improving antidepressant treatment, according to background information in the article. It is known that polymorphisms in the serotonin transporter gene (5-HTT) may influence antidepressant response to selective serotonin reuptake inhibitors.

Hyeran Kim, MD, of Sungkyunkwan University School of Medicine, and Korean colleagues conducted a study to determine whether there were significant associations between the efficacy of norepinephrine reuptake inhibitors and norepinephrine transporter polymorphisms and also between selective serotonin reuptake inhibitor efficacy and 5-HTT polymorphisms.

If confirmed, these associations could provide a basis for predicting response to antidepressants in these classes. The study evaluated 241 Korean patients with major depression who were treated for six weeks with fluoxetine or sertraline (136 patients) or nortriptyline (105). The average age at onset of major depressive disorder among these patients was in the early to mid-fifties.

The researchers found that the presence of certain genetic variations, alone or in combination, was associated with response and non-response to therapy with both classes of antidepressants.

They wrote that their analysis suggests that patients carrying the GG polymorphism of NET G1287A have a statistically significantly superior rate of response to norepinephrine reuptake inhibitor treatment than to selective serotonin reuptake inhibitor treatment (83.3 percent vs. 58.7 percent).

"… this study demonstrates that the responses to antidepressants with different targets have significant associations with homologous monoamine transporter gene polymorphisms. Our data confirm a relationship between SSRI response and 5-HTT polymorphisms, and establish an association between NRI response and the NET G1287A polymorphism.

We also found that the 5-HTTLPR s/l variation plays a role in the treatment of depression with both NRI and SSRI agents. The results of this study need to be confirmed in other populations, using selective NRIs other than nortriptyline. Additional studies in younger populations with depression are also needed. Confirmation of these preliminary findings would permit refined pharmacogenetic selection of antidepressant treatment."