Abstract
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.
Highlights
IntroductionKnown as major depression, is the most common mental disorder that is the leading cause of disability worldwide
Major depressive disorder, known as major depression, is the most common mental disorder that is the leading cause of disability worldwide
Effect of sildenafil on the activity of antidepressant drugs in the forced swim test The effect of sildenafil on the antidepressant-like activity of sertraline in the forced swim test in mice is shown in Fig. 1a (one-way ANOVA: F(4, 55) = 30.86, p < 0.0001)
Summary
Known as major depression, is the most common mental disorder that is the leading cause of disability worldwide. Antidepressant drugs, first introduced in the 1950s, remain the mainstay of treatment of Naunyn-Schmiedeberg's Arch Pharmacol (2017) 390:339–349 depression and are one of the most widely taken medicines (Lopez-Munoz and Alamo 2009). High rates of comorbidity between depression and various somatic and/or mental illnesses result in a need for simultaneous treatment with antidepressants and other medications. This requires special caution, especially concerning drug interactions (Kang et al 2015; Lopez-Munoz and Alamo 2009; Iosifescu et al 2004). For severe and life-threatening depression that does not respond to antidepressants drugs, electroconvulsive therapy (ECT) is frequently used (Payne and Prudic 2009)
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