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Serotonin transporter polymorphisms and side effects in antidepressant therapy--a pilot study
Johannes Popp1, Stefan Leucht, Stephan Heres
1Technische Universität München, Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar Ismaninger Str. 22 81675 München, Germany.
Pharmacogenomics
|March 7, 2006
Summary
Genetic variations in serotonin transporter (HTT-VNTR and HTTLPR) influence antidepressant side effects, particularly with SSRIs and TCAs. Mirtazapine tolerability was unaffected by these genetic factors.
Area of Science:
- Pharmacogenetics
- Neuroscience
- Clinical Psychiatry
Background:
- Antidepressant therapy efficacy and tolerability can be influenced by genetic factors.
- The serotonin transporter gene plays a crucial role in regulating serotonin levels, impacting mood and response to antidepressants.
Purpose of the Study:
- To investigate the association between serotonin transporter variable number of tandem repeat (HTT-VNTR) and serotonin transporter-gene-linked polymorphic region (HTTLPR) polymorphisms and the development of side effects during antidepressant treatment.
- To determine if specific genotypes of these polymorphisms predict adverse drug events in patients undergoing pharmacotherapy for depression.
Main Methods:
- A cohort of 109 depressive in-patients receiving various antidepressants was studied.
- Side effects were evaluated using a modified Dosage Record and Treatment Emergent Symptoms scale (DOTES) after four weeks of hospitalization.
- Genotype data for HTT-VNTR and HTTLPR polymorphisms were analyzed for associations with side effects using Fisher's exact test.
Main Results:
- Patients treated with serotonin transporter (HTT)-blocking antidepressants (SSRIs, TCAs) showed significantly higher side effect incidence with specific HTT-VNTR genotypes (2.10/2.10) and HTTLPR genotypes (s/s).
- No association between HTT-VNTR polymorphism and side effects was observed in patients treated with mirtazapine, likely due to its different mechanism of action.
- Combined genotypes of both polymorphisms significantly predicted adverse drug events in patients on HTT-blocking antidepressants, with high-risk genotypes experiencing substantially more side effects.
Conclusions:
- The study supports the hypothesis that HTT-VNTR and HTTLPR polymorphisms influence the tolerability of antidepressants that primarily act via serotonin transporter inhibition (e.g., SSRIs, TCAs, venlafaxine).
- Mirtazapine tolerability appears independent of these serotonin transporter gene polymorphisms, suggesting a distinct pharmacogenetic profile.
- Further research is warranted to confirm these findings, given the limitations of treatment heterogeneity and concomitant therapies in the current study.
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