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Serotonin transporter gene and response to lithium augmentation in depression.

Author(s): Stamm TJ, Adli M, Kirchheiner J, Smolka MN, Kaiser R, Tremblay PB, Bauer M

Affiliation(s): Department of Psychiatry and Psychotherapy, Charite-Universitatsmedizin Berlin, Campus Charite Mitte, Berlin, Germany. thomas.stamm@charite.de

Publication date & source: 2008-04, Psychiatr Genet., 18(2):92-7.

Publication type: Clinical Trial, Phase II; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: The serotonin (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) is associated with better response to selective serotonin reuptake inhibitors in Caucasian patients carrying the long (l)-allele. In contrast, augmentation of antidepressant drugs with pindolol has been shown to improve responsiveness to antidepressants in short (s)-allele carriers. Lithium augmentation is a well-established strategy for overcoming treatment resistance. In this study, the 5-HTTLPR allele variant's effect on lithium augmentation was analyzed in antidepressant-nonresponsive patients. METHODS: We measured remission rates during lithium augmentation in 50 depressed patients genotyped for the 5-HTTLPR. All patients took part in phase II of the German Algorithm Project, a prospective study for the evaluation of a standardized stepwise drug treatment regimen. For statistical analysis, the Cox regression model including several clinical factors besides the 5-HTTLPR was used. RESULTS: Only the genotype of the 5-HTTLPR (P<0.006) showed a signficant influence on remission. Patients homozygous for the s-allele had a more favorable response compared with those heterozygous (hazard ratio=6.9; P=0.005) or homozygous for the l allele (hazard ratio=4.5; P=0.003). CONCLUSION: The findings support a differential effect of the 5-HTTLPR gene on primary treatment with antidepressants and treatment augmentation. Similar to the observations with pindolol, s/s-allele patients showed a higher benefit from lithium augmentation than did patients carrying other 5-HTTLPR genotypes. Thus, the s/s genotype might predict an individual's risk of antidepressant nonresponsiveness and sensitivity to augmentative drugs such as lithium.

Page last updated: 2008-06-22

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