Serotonin transporter gene and response to lithium augmentation in depression.
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).


CONCLUSIONS
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.
Stamm
Thomas J
TJ
Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany. thomas.stamm@charite.de
Adli
Mazda
M
Kirchheiner
Julia
J
Smolka
Michael N
MN
Kaiser
Rolf
R
Tremblay
Pierre Benoit
PB
Bauer
Michael
M
D000328:Adult; D000483:Alleles; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003866:Depressive Disorder / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000150:complications; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016896:Treatment Outcome
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D016651:Lithium Carbonate