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Possible Biologic Basis to SSRI-Related Suicidal Ideation

Initial genetic screening implicates markers within the glutamate signaling pathway.

Why do some patients taking antidepressants become vulnerable to suicidal ideation? To explore a possible biologic basis for this adverse effect, researchers used data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. The study population consisted of 1862 patients (age range, 18–75) who had received initial treatment with citalopram for depression and had genotype information available. Cases were 120 patients who self-reported treatment-emergent suicidal ideation; controls were the remaining 1742 patients. The investigators examined 68 candidate genes involved with glutamate, serotonin, dopamine, norepinephrine, and neurotrophin systems, as well as other pathways; within these, 768 single-nucleotide polymorphisms (SNPs) were chosen to sample common variation.

No between-group differences were found in clinical variables known to predict suicide. In participants with suicidal ideation, its onset developed relatively early in treatment (within 14 days in 21%; within 28 days in 92%). Two high-risk allele markers within the GR1K2 and GR1A3 genes, both of which are involved with encoding ionotropic glutamate receptors, were significantly associated with suicidal ideation, independent of citalopram dose.

Comment: Although the 68 candidate genes studied here seem pertinent, many other genes may also be influential, and many other genetic and nongenetic factors not yet identified may contribute to suicidal ideation (or suicide) in patients taking antidepressants. The identified alleles affect AMPA and kainite glutamate receptors known to change with antidepressant medications. Soon, perhaps, inexpensive, office-based genetic screening tools may permit clinicians to identify individual vulnerabilities and preemptively avoid specific adverse medication effects.

— Joel Yager, MD

Published in Journal Watch Psychiatry January 7, 2008

Citation(s):

Laje G et al. Genetic markers of suicidal ideation emerging during citalopram treatment of major depression. Am J Psychiatry 2007 Oct; 164:1530.

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