Genetic variants in combination with early partial improvement as a clinical utility predictor of treatment outcome in major depressive disorder: the result of two pooled RCTs.

Abstract

Pharmacogenetics may allow for a personalized treatment, but a combination with clinical variables may further enhance prediction. In particular, in the present paper, we investigated early partial improvement (EPI) defined as 20% or more improvement by rating scales 2  weeks after treatment, in combination with selected gene variants as a predictor of treatment outcome in patients with major depressive disorder. Two randomized controlled trials with 168 Japanese depressed patients were used. A stepwise multiple linear regression model with HAM-D score change at week 6 as the dependent variable and genotypes, EPI, baseline HAM-D score, age and sex as independent variables was performed in paroxetine, fluvoxamine and milnacipran, respectively, to estimate the prediction of HAM-D change at week 6. In the paroxetine sample, only EPI (P<0.001) was significantly associated with HAM-D change (n=81, R(2)=0.25, P<0.001). In the fluvoxamine sample, 5-HTTLPR La/Lg, S (P=0.029), FGF2 rs1449683C/T (P=0.013) and EPI (P=0.003) were associated with HAM-D change (n=42, R(2)=0.43, P<0.001). In the milnacipran sample, HTR-1A-1019C/G (P=0.001), ADRA2A-1297C/G (P=0.028) and EPI (P<0.001) were associated with outcome (n=45, R(2)=0.71, P<0.001). EPI in combination with genetic variants could be a useful predictor of treatment outcome and could strengthen the practical use of pharmacogenetic data in clinical practice.

• Authors: M Kato, A Serretti, S Nonen, Y Takekita, M Wakeno, J Azuma, T Kinoshita
• Journal: Translational psychiatry (Transl Psychiatry) Vol. 5 Pg. e513 (Feb 24 2015) ISSN: 2158-3188 [Electronic] United States
• PMID: 25710119 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• ADRA2A protein, human
• Antidepressive Agents
• Antidepressive Agents, Second-Generation
• Cyclopropanes
• FGF20 protein, human
• HTR1A protein, human
• Receptors, Adrenergic, alpha-2
• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins
• Receptor, Serotonin, 5-HT1A
• Paroxetine
• Fibroblast Growth Factors
• Milnacipran
• Fluvoxamine

Topics

• Age Factors
• Antidepressive Agents (therapeutic use)
• Antidepressive Agents, Second-Generation (therapeutic use)
• Cyclopropanes (therapeutic use)
• Depressive Disorder, Major (diagnosis, drug therapy, genetics)
• Female
• Fibroblast Growth Factors (genetics)
• Fluvoxamine (therapeutic use)
• Humans
• Japan
• Male
• Middle Aged
• Milnacipran
• Paroxetine (therapeutic use)
• Psychiatric Status Rating Scales (statistics & numerical data)
• Receptor, Serotonin, 5-HT1A (genetics)
• Receptors, Adrenergic, alpha-2 (genetics)
• Serotonin Plasma Membrane Transport Proteins (genetics)
• Sex Factors
• Treatment Outcome