Early response plus genetic variants strengthen antidepressant outcome prediction

By Lucy Piper, Senior medwireNews Reporter

Considering genetic variants in combination with early partial improvement (EPI) could be useful for predicting antidepressant outcome, say researchers.

“[W]e propose a practical method to apply results of pharmacogenetic studies into clinical practice”, they explain in Translational Psychiatry.

The team analysed data from two randomised controlled trials involving 168 Japanese patients with major depression who were treated with paroxetine, fluvoxamine or milnacipran and looked at the effects of EPI and known candidate genetic variants on outcome.

Treatment response to paroxetine at 6 weeks was primarily predicted by EPI, defined as at least a 20% improvement in scores on the Hamilton Rating Scale for Depression (HAM-D) 2 weeks after starting treatment, in multiple linear regression models.

It was also a significant predictor of milnacipran response and, to a lesser extent, response to fluvoxamine.

But response to milnacipran was also influenced by carriage of the C allele of the alpha 2A-adrenergic receptor (ADRA2A) and the C allele of the serotonin-1A receptor (HTR1A). F And the L_A allele of the serotonin transporter gene promoter polymorphism (5-HTTLPR) and the T allele of basic fibroblast growth factor (FGF2) influenced response to fluvoxamine.

M Kato (Kansai Medical University, Osaka, Japan) and co-researchers estimate from the regression equations that patients carrying the 5-HTTLPR L_A, HTR1A C, ADRA2A C and FGF2 T alleles could be expected to improve by 41.6% with paroxetine and 72.0% with fluvoxamine and deteriorate by 13.9% with milnacipran.

If the patients also had an EPI, however, improvement in HAM-D score at 6 weeks could reach 75.5%, 91.8% and 40.5%, respectively.

“EPI with specific genetic variants could be a useful predictor of treatment outcome and help personalized treatment of depression”, the team concludes.

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