GNB3 Gene and Antidepressant Toxicity

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Antidepressants like Lexapro and Nortriptyline work by increasing the amounts of certain natural substances in the brain that are needed to maintain mental balance. Nortriptyline is also sometimes used to treat panic disorders, and post-herpetic neuralgia and sometimes to help people stop smoking.

GNB3 encodes a protein complex that is involved in the signaling cascade following monoamine receptor activation. A functional polymorphism in this gene (C825T) has been associated with a response to antidepressants. Several lines of evidence suggest that GNB3 moderates improvement in the neurovegetative symptoms of depression (such as sleep and appetite) and related adverse reactions independently of changes in core mood symptoms.

In a study[1] of 811 subjects with major depression undergoing treatment with either escitalopram (Lexpro) or nortriptyline, the C825T SNP in GNB3 was genotyped. The study showed that the TT genotype was significantly associated with a superior response to nortriptyline and these effects were specific to improvements in neurovegetative symptoms. In addition, the same genotype predicted fewer incidents of treatment-emergent insomnia and greater weight gain on the same drug.

People with rs5443 CC or CT genotypes and Depressive Disorder, who were treated with escitalopram (Lexapro) or nortriptyline showed less improvement in symptoms like sleep and appetite compared to people with TT genotype. They also had decreased risk for weight gain.

Conversation Tags

Antidepressants, GNB3