Lipoic acid prevents mirtazapine-induced weight gain in mice without impairs its antidepressant-like action in a neuroendocrine model of depression.

Mirtazapine (MIRT) is a multi-target antidepressant used in treatment of severe depression with promising efficacy, but also with important side effects, mainly sedation and weight gain. Thus, the present study aimed to test the effects of the neuroprotective antioxidant lipoic acid (ALA) in the reversal of weight and metabolic changes induced by MIRT in corticosterone-induced depression model in mice, as well as proposed mechanisms for their association antidepressant and pro-cognitive effects. To do these male Swiss mice received Tween 80 (control), corticosterone (CORT 20 mg / kg), MIRT (3 mg / kg) and ALA (100 or 200 mg / kg), alone or associated for 21 days. After this, the animals were subjected to behavioral tests for affective and cognitive domains. Daily weight changes, blood cholesterol fractions and corticosterone were measured. Also, hippocampus (HC) protein expression of the serotonin transporter (SERT), synaptophysin, protein kinase B-Akt (total and phosphorylated) and the cytokines IL-4 and IL-6 were investigated. CORT induced a marked depression-like behavior, memory deficits, metabolic changes (total cholesterol and LDL) and increased serum corticosterone. Also, CORT increased SERT expression in the HC. MIRT alone or combined with ALA sustained its antidepressant-like effect, as well as reversed CORT-induced impairment in spatial recognition memory. Additionally, the association MIRT+ALA200 reversed the weight gain induced by the former antidepressant, as well as reduced serum corticosterone levels and SERT expression in the HC. ALA alone induced significant weight loss and reduced total cholesterol and HDL fraction. Our findings provide promising evidence about the ALA potential to prevent metabolic and weight changes associated to MIRT, without impair its antidepressant and pro-cognition actions. Therefore, ALA+MIRT combination could represent a new therapeutic strategy for treating depression with less side effects.

Hepatopatía inflamatoria asintomática asociada a uso de mirtazapina: reporte de caso / Asymptomatic inflammatory liver disease associated with mirtazapine use: case report

Resumen La mirtazapina es un antidepresivo atípico con características complejas, que incluye actividad agonista/antagonista en una amplia variedad de receptores que produce efectos terapéuticos en la ansiedad, depresión y el sueño. Sin embargo, se han reportado casos de lesión hepática inducida por antidepresivos con ausencia de sintomatología, bajo la forma de variantes hepatocelular, colestásica y mixta. Este es el caso de una paciente que de carácter incidental presenta cambios en la analítica hepática tras el uso de mirtazapina a partir del cual se hace una breve revisión de la evidencia encontrada hasta el momento.

Mirtazapine is an atypical antidepressant with complex characteristics, including agonist/antagonist activity at a wide variety of receptors that produces therapeutic effects on anxiety, depression and sleep disorder. However, cases of antidepressant-induced liver injury with no symptoms have been reported, in the form of hepatocellular, cholestatic, and mixed variants. This is the case of a patient who incidentally presents changes in liver analysis after the use of mirtazapine, from which a brief review of the evidence found so far is made.