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.