Background:
Orosomucoid, an acute-phase reactant (APR), carries basic drugs including antidepressants. Elevated levels have been reported in depressed patients. It has yet to be established whether concentration influences antidepressant response. Its gene, ORMI, is polymorphic and has three common codomi-nant alleles ORM*F1, *F2 and *S. The variants have differing pharmacokinetic properties that potentially alter plasma profile and blood-brain barrier transport of antidepressants influencing tolerance and efficacy.
Methods:
A total of 157 out-patients in a trial of fluoxetine vs. nortriptyline were genotyped for the ORMl variants. Plasma concentrations of APRs were also measured. Outcomes were tolerance and response. Tolerance was defined as the completion of a 6-week trial and response as an improvement of greater than 60% on the Montgomery-Asperg Depression Rating Scale at 6 weeks. Groups were compared using one-way ANOVA and chi-squared tests. Outcome predictions were performed using binomial logistic regression.
Results:
Individuals with an ORM1*F allele were more likely to tolerate antidepressants [odds ratio (OR) = 4.707, 95% confidence interval (CI) 1.769−12.527, P = 0.002). Higher orosomucoid concentrations were found in antidepressant nonresponders (91.4% vs. 79.1%, F-stat 6.071, P = 0.015). For every 1% increase in orosomucoid, the odds of response were decreased (OR = 0.984, 95% CI 0.971−0.997, P = 0.018).
Conclusions:
The two effects of orosomucoid – polymorphism affecting tolerability and concentration affecting efficacy – emphasize its importance in the handling of antidepressants.
