Effectiveness of certain antidepressants may be influenced by gene variations of individuals

October 03, 2006

Whether specific types of antidepressants are effective for patients with late-life major depression may depend if they have certain genetic variations, according to a study in the October 4 issue of JAMA.

Initial drug treatments fail in 30 percent to 40 percent of patients with major depression. Pharmacogenetic (the relation of genetic factors to variations in response to drugs) prediction of response is one possibility for improving antidepressant treatment, according to background information in the article. Polymorphisms (occurrence in more than one form) in the serotonin transporter gene (5-HTT) may influence antidepressant response to selective serotonin reuptake inhibitors (SSRIs - a class of antidepressant drugs).

Hyeran Kim, M.D., of Sungkyunkwan University School of Medicine, Seoul, Korea, and colleagues conducted a study to determine whether there were significant associations between the efficacy of norepinephrine reuptake inhibitors (NRIs - a class of antidepressant drugs) and norepinephrine transporter (NET) polymorphisms and also between SSRI efficacy and 5-HTT polymorphisms. If confirmed, these associations could provide a basis for predicting response to certain antidepressants. The study included 241 Korean patients with major depression. They were treated for 6 weeks with an SSRI (fluoxetine or sertraline; n = 136) or an NRI (nortriptyline; n = 105) antidepressant. The average age at onset of major depressive disorder among these patients was in the early to mid-50s.

The researchers found that the presence of certain polymorphisms, alone or in combination, was associated with response and non-response to therapy with SSRIs or NRIs.

They write that their data analysis suggests that patients carrying the GG polymorphism of NET G1287A have a statistically significantly superior rate of response to NRI treatment than to SSRI 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," the researchers write. "Confirmation of these preliminary findings would permit refined pharmacogenetic selection of antidepressant treatment."
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(JAMA. 2006;296:1609-1618. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: This study was supported by grants from the Korea Health Research and Development Project, Ministry of Health and Welfare, Republic of Korea. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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