Beneficial omega-3 fatty acid combination treatment for depression: synergism with fluoxetine and mirtazapine at antidepressant or ineffective doses.

LAINO, C., FONSECA C., STERIN-SPEZIALE N, REINÉS, A.

EUROPEAN JOURNAL OF PHARMACOLOGY

Enviado

Año: 2009 p. 1 - 29

0014-2999

Rationale Despite the advances in the psychopharmacology, the treatment of depressive disorders is still not satisfactory. Side effects and resistant to antidepressant drugs are the greatest complications during treatment.  Based on recent evidence, omega-3 fatty acids may influence vulnerability and outcome in depressive disorders. Objective The aim of the present work was to analyze in rats the antidepressant effect of omega-3 fatty acids supplementation alone as well as in combined chronic treatments with antidepressants fluoxetine (FLX) or mirtazapine (MTZ) in the forced swimming test (FST). Materials and Methods Male Wistar rats were tested in the FST after chronic (16 days) treatment with FLX (1 or 10 mg/kg/day) or MTZ (1 or 20 mg/kg/day) alone or in combination with chronic supplementation with omega-3 fatty acids (720 mg/kg/day). Results Chronic diet supplementation with omega-3 fatty acids produced concentration-dependent antidepressant-like effects in the FST. A sub-effective dose of FLX or MTZ combined with omega-3 fatty acids showed significantly higher antidepressant effects than omega-3 fatty acids alone while FLX or MTZ effective doses rendered additive effects in combination with omega-3 fatty acid supplementation. Brain phospholipid composition was not modified after 16 day administration of omega-3 fatty acids. Conclusions Chronic coadministration of omega-3 fatty acids and inactive doses of FLX or MTZ showed a synergistic antidepressant-like effect without modifying brain phospholipid classes. This therapeutic approach might represent benefits in patients with depression resistant to conventional treatments and even may contribute to lowering the appearance of antidepressant dose-dependent side effects.