Sildenafil SSRIs

Several medications have been suggested as antidotes for the sexual side effects associated with antidepressant therapy. Bupropion, 75 or 150 mg/day, has been added to an SSRI regimen with some success in terms of improving libido (Labbate and Pollack 1994). Sildenafil has been used on an as-needed basis before sexual activity (Fava et al. 1998). 

Many patients do consider these problems to be a nuisance rather than a reason to terminate SSRI therapy. Others find these problems intolerable. A wide range of treatments have been tried including dopamine agonists including bupropion, yohimbine, cyproheptadine, and sildenafil. Most of these treatments had only anecdotal and open label studies to support their usefulness. However, sildenafil was found to be superior to placebo in a double-blind study ( 445). 

The available case reports in the FDA AERS support the published literature that there are pharmacokinetic interactions between St. John s wort and CYP3A4 and/or p-glycoprotein substrates, such as cyclosporine, levonorgestrel/estradiol and sildenafil, and pharmacodynamic interactions with the SSRIs or MAOI. Subsequent clinical studies including those conducted via a CDER clinical pharmacology research cooperative agreement (14—16) provided mechanistic basis of many of these interactions (refer to Chapter 4). 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Sexual dysfunction is a common adverse effect of SSRIs and various treatments have been proposed, of which sildenafil is the only strategy with consistent support from controlled trials. Sildenafil is metabolized by CYP3A4, which is inhibited by fluvoxamine. The effects of fluvoxamine (100 mg/day for 10 days) on the pharmacokinetics of sildenafil (50 mg orally) has been evaluated in 12 healthy men (mean age 25 years) using a doubleblind, placebo-controlled, crossover design (46). Fluvoxamine increased the AUC of sildenafil by about... 

For sexual dysfunction, can augment with bupropion, sildenafil, vardenafil, or tadalafil, or switch to a non-SSRI such as bupropion or mirtazapine... 

B Sexual dysfunction is generally believed to be a dose-dependent side effect with SSRIs and may be relieved or prevented with lower doses. Although RH may run the risk of relapse at a lower dose, many patients will achieve a therapeutic response at lower doses. If this approach is unsuccessful, bupropion is an excellent antidote and may also provide additional antidepressant effects (i.e., augmentation). Sildenafil has actually been found to reverse SSRI-induced sexual dysfunction but is an expensive alternative with potential cardiovascular complications that should only be considered after other measures fail. 

A4 Barbiturates, carbamazepine, corticosteroids, efavirenz, phenytoin, rifampin, troglitazone Antiarrhythmics, antidepressants, azole antifungals, benzc iazepines, calcium channel blockers, cyclosporine, delavirdine, doxorubicin, efavirenz, erythromycin, estrogens, HIV protease inhibitors, nefazodone, paclitaxel, proton pump inhibitors, HMG-CoA reductase inhibitors, rifabutin, rifampin, sildenafil, SSRIs, tamoxifen, trazodone, vinca anticancer agents... 

Retrospective analysis of clinical study data su ested that SSRIs and tricyclic antidepressants did not alter sildenafil pharmacokinetics. However, in one study fluvoxamine was found to modestly increase the levels and vascular effects of sildenafil. 

The manufacturer notes that population pharmacokinetie analysis of elin-ical study data indieate that inhibitors of cytochrome P450 isoenzyme CYP2D6 such as SSRIs and tricyclic antidepressants do not have any effect on the pharmacokinetics of sildenafil. However, in a double-blind, placebo-controlled study in healthy subjects, pre-treatment with fluvox-amine 50 mg daily for 3 days then 100 mg daily for 6 days increased the AUC of sildenafil 50 mg by 40%. This resulted in an inerease in the vascular effects of sildenafil. ... 

Sildenafil is principally metabolised by cytochrome P450 isoenzyme CYP3A4, and to a lesser extent by CYP2C9. Fluvoxamine probably raises sildenafil by inhibition of both of these isoenzymes. Grouping all SSRIs and tricyclics together in a retrospective analysis would not be a sensitive enough technique to have picked up this modest effect of fluvoxamine. 

There have been two reports of the management of SSRI-induced sexual adverse effects. First, in an 8-week prospective double-blind placebo-controlled trial of sildenafil 50-100 mg/day in 98 previously sexually functioning premenopausal women whose major depression had remitted on SSRIs, but who were also experiencing sexual dysfunction, sildenafil was associated... 

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