Acetylsalicylic acid accelerates the antidepressant effect of fluoxetine in the chronic escape deficit model of depression

Abstract

Evidence has accumulated suggesting that major depression is associated with dysfunction of inflammatory mediators. Moreover, antidepressants show an anti-inflammatory action possibly related to their clinical efficacy. An improvement in psychiatric symptoms has been recently reported in patients treated with anti-inflammatory drugs for other indications. These data imply that inflammation may be involved in the pathogenesis of depression and that anti-inflammatory drugs may be used as an adjunctive therapy. The aim of the present study was to evaluate the behavioural effect of the co-administration of acetylsalicylic acid (ASA, 45 mg/kg or 22.5 mg/kg) and fluoxetine (FLX, 5 mg/kg) in the chronic escape deficit model of depression. The chronic escape deficit model is based on the modified reactivity of rats to external stimuli induced by exposure to unavoidable stress and allows evaluation of the capacity of a treatment to revert the condition of escape deficit. In this model, FLX alone needs to be administered for at least 3 weeks to revert this condition. Our results show that combined treatment of fluoxetine and ASA completely reverted the condition of escape deficit by as early as 7 days, the effect being already partially present after 4 days. The effect was maintained after 14 and 21 days of treatment. ASA alone was ineffective at any time tested and the effect of fluoxetine was significant only at 21 days. These results, together with clinical data from preliminary results, suggest that ASA might accelerate the onset of action of selective serotonin reuptake inhibitor antidepressants.

Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment

“…In addition, the bi-directional crosstalk between SSRI administration and inflammation has been described also by studies investigating the effects of antiinflammatory drugs on antidepressant efficacy. Indeed, experimental and clinical studies have shown that anti-inflammatory drugs, such as celecoxib or aspirin, can either improve (Akhondzadeh et al, 2009;Andrade, 2014;Brunello et al, 2006) or impair treatment outcome (Warner-Schmidt et al, 2011). …”

The effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder: A randomized clinical trial

“…Rahola (2012) also reported that aspirin adjacent to antidepressants significantly improved depression symptoms (38). Another study also reported the effectiveness of fluoxetineaspirin in alleviating depression symptoms (39). Savitz et al (2012) also conducted a study on 120 patients with bipolar disorder who were in depressive phase, and found that aspirin significantly reduced the side effects of antidepressants and significantly improved depression symptoms (36).…”

La interfaz entre neurología y psiquiatría: el caso de la esclerosis múltiple [translation of “The interface between neurology and psychiatry: the case of multiple sclerosis” by Rodolfo Zaratiegui]

“…Del mismo modo, la aspirina aceleró el comienzo de la acción de la fluoxetina de 3 semanas a sólo 1 en ratas estudiadas utilizando un modelo de depresión consistente en cuantificar las fallas de escape ante situaciones aversivas. Las ratas pretratadas con aspirina evitaban significativamente mejor estímulos dolorosos luego de una semana de la administración de fluoxetina con aspirina, comparadas con aquellas tratadas con aspirina o fluoxetina solamente (Brunello 2006).…”