Does pretreatment testing for serotonin transporter polymorphisms lead to earlier effects of drug treatment in patients with major depression? A decision-analytic model.
BACKGROUND
An estimated 30% to 40% of patients with depression do not sufficiently respond to treatment with selective serotonin reuptake inhibitors (SSRIs) and the period in which treatment efficacy can be assessed is relatively long. Therefore, a test to identify potential nonresponders could be useful in the treatment of depression. Serotonin transporter gene (SLC6A4) variations have been reported to account for differences in the way individuals respond to SSRI treatment.


OBJECTIVE
A decision-analytic model was used to assess whether pretreatment genetic testing for 5-HTTLPR, a polymorphism of the SLC6A4 genotype, could be an efficient tool in the treatment of depression.


METHODS
A theoretical clinical decision-analytic model was constructed to compare the current treatment strategy in The Netherlands with an alternative strategy for the treatment of depression. Under treatment guidelines in The Netherlands, all patients with depression receive SSRI treatment (nontesting strategy). Under the alternative strategy, genetic testing would be performed to identify which class of antidepressant would be the best choice for initiation of treatment (genetic testing strategy). Probabilities (predicted results) for this model were based on data from previous studies and the opinions of experts in the field of psychopharmacology. To test the robustness of the model, 6- and 12-week remission rates for patients treated with SSRIs were varied in a sensitivity analysis using a predetermined range that was established based on expert opinion. Threshold analyses were performed on the parameters of serotonin transporter genotype frequency and response and nonresponse rates for patients receiving SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs) to determine the value for a variable at which it could be concluded that a change in treatment strategy would be preferred.


RESULTS
When genetic testing was performed before an antidepressant was prescribed, 64.6% of patients were predicted to be in remission after 6 weeks of treatment compared with 60.0% of patients who did not receive genetic testing. After 12 weeks, 79.5% of patients in the testing group who received an SNRI as initial treatment and 83.2% of those who received a TCA initially were predicted to be in remission compared with 76.7% of patients in the nontesting group. Sensitivity analyses indicated that the model was robust to variation of probability estimates within their plausible ranges. However, these findings were based on a theoretic model and did not include cost assessment. Pretreatment genetic testing must be evaluated further in randomized clinical trials and costs must be assessed before implementing this strategy in routine psychiatric practice can be recommended.


CONCLUSIONS
The findings of this study suggest that performing genetic testing before prescribing antidepressant treatment may lead to greater numbers of patients experiencing remission early in treatment.
Smits
Kim M
KM
Department of Epidemiology, Maastricht University, Maastricht, The Netherlands. kim.smits@epid.unimaas.nl
Smits
Luc J M
LJ
Schouten
Jan S A G
JS
Peeters
Frenk P M L
FP
Prins
Martin H
MH
D000928:Antidepressive Agents / Q000627:therapeutic use*; D003661:Decision Support Techniques; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D017850:Economics, Pharmaceutical; D006801:Humans; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D012074:Remission Induction; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016896:Treatment Outcome
D000928:Antidepressive Agents; D050486:Serotonin Plasma Membrane Transport Proteins