Effect of sildenafil on the activity of some antidepressant drugs and electroconvulsive shock treatment in the forced swim test in mice

Sildenafil, a potent and selective inhibitor of phosphodiesterase type 5, is used clinically to treat erectile dysfunction and pulmonary arterial hypertension. It is often taken by patients suffering from depression and receiving antidepressant drug treatment. However, its influence on the efficacy of antidepressant treatment was not sufficiently studied. Therefore, the aim of the present study was to investigate the influence of sildenafil on the anti-immobility action of several antidepressant drugs (i.e., sertraline, fluvoxamine, citalopram, maprotiline, trazodone, and agomelatine) as well as on antidepressant-like effect of electroconvulsive stimulations in the forced swim test in mice. The obtained results showed that acute sildenafil treatment enhanced the antidepressant-like activity of all of the studied drugs. The observed effects were not due to the increase in locomotor activity. The interactions between sildenafil and sertraline, maprotiline, and trazodone were pharmacodynamic in nature, as sildenafil did not affect concentrations of these drugs neither in serum nor in brain tissue. Increased concentrations of fluvoxamine, citalopram, and agomelatine in brain tissue evoked by sildenafil co-administration suggest that pharmacokinetic interactions between sildenafil and these drugs are very likely. Sildenafil injected acutely did not alter the antidepressant-like efficacy of electroconvulsive stimulations in mice, as assessed in the forced swim test. Interestingly, repeated (14 days) administration of sildenafil decreased the anti-immobility action of the electroconvulsive stimulations. In conclusion, the present study shows that sildenafil may alter the effectiveness of antidepressant treatment. Further studies are warranted to better characterize the influence of sildenafil on the activity of antidepressant drugs and electroconvulsive therapy.