Orosomucoid influences the response to antidepressants in major depressive disorder

Orosomucoid, an acute phase protein, carries basic drugs including antidepressants in plasma. Elevated levels have been reported in patients with depression. It has yet to be established whether orosomucoid concentration influences antidepressant response. The orosomucoid gene (ORM1) is polymorphic and the protein isoforms have differing pharmacokinetic properties which could alter plasma profile and blood brain barrier transport of antidepressants. Outpatients (n = 157) in a randomised control trial of fluoxetine versus nortriptyline were genotyped for the ORM1 variants. Plasma concentrations of acute phase proteins were also measured. Outcomes were the completion of an adequate six week trial of antidepressant and response. Response was defined as an improvement >/=60% on the Montgomery-Asperg Depression Rating Scale (MADRS) over six weeks. The first notable finding was that individuals with an ORM1*S/*S genotype were less likely to complete an adequate six week trial of an antidepressant (OR = 4.707, 95% CI 1.769-12.527, P = 0.002). The second was that higher orosomucoid concentrations were found in antidepressant non-responders (91.4%) than responders (79.1%) (F1, 106 = 5.669, P = 0.019). These findings highlight the potential importance of variables such as orosomucoid which impact on drug availability on the therapeutic efficacy of antidepressant drugs.