Drug-induced sexual dysfunction is a common problem occurring during treatment of a variety of illnesses, including depression, schizophrenia, hypertension and diabetes mellitus. Antidepressants, among all psychotropics, are most likely to cause sexual dysfunction, and orgasm disturbances (delayed ejaculation or anorgasmia) are the type most commonly associated with them. The association of antidepressants and decreased libido must be viewed cautiously, since 50% to 90% of untreated patients with depression experience decreased libido. In fact, many patients with depression experience increased libido when they are successfully treated with an antidepressant. Similarly, although antidepressants have been reported to cause arousal disturbances, erectile dysfunction is more likely to be related to depression or secondary to drug-induced ejaculatory delay. Indeed, the relationship between sexual dysfunction and depression seems to be bidirectional, in that the presence of either one of these conditions may trigger or exacerbate the other, and the treatment of one condition may improve the other. Treatment-emergent sexual dysfunction can be an added source of distress for patients with depression, which, if left untreated, may prolong or worsen the illness, compromise treatment outcome, affect quality of life, and lead to noncompliance with treatment. The overall prevalence rate of sexual dysfunction in medicated patients with major depressive disorder is estimated to be more than 50%. Tricyclic antidepressant-related sexual dysfunction is particularly high, although the lack of available standardized assessment measures, when these drugs were in development, limits comparison with current agents. Limited evidences suggested that amitriptyline, clomipramine and imipramine are more often associated with alterations in orgasm, desire and even arousal. Among monoamine oxidase inhibitors, moclobemide is associated with low incidence of sexual dysfunction.
Selective serotonin reuptake inhibitors (selective serotonin reuptake inhibitors) have been associated with adverse effects on all three phases of sexual function, although their most prominent effect is delayed orgasm/ejaculation and anorgasmia. selective serotonin reuptake inhibitors have also been reported to cause decreased libido. The consensus from a series of well-designed comparative studies is that up to 60% of patients receiving selective serotonin reuptake inhibitors report some form of treatment emergent sexual dysfunction. Interestingly, in a recent large series of patients with sexual dysfunction, the use of selective serotonin reuptake inhibitors, but not other antidepressants or benzodiazepines, negatively affected almost all the components of the sexual response cycle. Moreover, the use of selective serotonin reuptake inhibitors was associated with a mild hyperprolactinemia. The effects of selective serotonin reuptake inhibitors on arousal and orgasm may be mediated by stimulation of serotonergic projections from medullary raphe nuclei to the spinal cord. The decrease of libido may be due to decreased dopaminergic activity mediated by stimulation of serotoninergic projections from midbrain raphe nuclei to the mesolimbic dopamine system. In particular, although these effects seem to be related to the stimulation of serotonin, especially on 5HT2 receptors, other mechanisms are likely to be involved. For example, the high rate of sexual dysfunction associated with paroxetine ( i.e. anorgasmia and erectile dysfunction) may be attributed also to cholinergic receptor blockade and nitric oxide synthase-inhibiting effects.
Reboxetine, a norepinephrine transporter inhibitor, has demonstrated superiority in sexual function outcomes compared with different selective serotonin reuptake inhibitors (i.e. citalopram, paroxetine and fluoxetine). There is some evidence that noradrenergic effects may mitigate the serotonin influence on sexual function. Indeed, treatment-emergent sexual dysfunction with duloxetine and venlafaxine, two common serotonin noradrenaline reuptake inhibitors, has been demonstrated to be significantly lower, when compared with other selective serotonin reuptake inhibitors. Mirtazapine-induced sexual dysfunction are significantly less common than with selective serotonin reuptake inhibitors, serotonine/noradrenaline reuptake inhibitors, and Tricyclic antidepressant. Mirtazapine stimulates noradrenergic and serotoninergic activity through its agonist effect on postsynaptic receptor 5-HTia and concurrent antagonist effect on 5-HT2 and 5-HT3 receptors; the 5-HT2 blockade prevents serotonin -mediated adverse effects on sexual function.
With its dual inhibition of norepinephrine and dopamine reuptake, bupropion is devoid of any direct effects on the serotonin system and has the potential to positively affect arousal and desire. In fact, it has been demonstrated that bupropion resulted in less sexual dysfunction than fluoxetine, paroxetine, or sertraline, with regard to orgasm dysfunction. sexual dysfunction is considered as one of the most common reasons for patients’ dropping out of treatment with antidepressant. Patients should be counseled about the potential for antidepressant-induced changes in their sexual function and told that such changes can be managed. Options include waiting for tolerance to develop, decreasing the dosage, giving drug holidays, augmenting therapy with an additional drug, and switching to an alternative antidepressant less likely to cause sexual dysfunction. Nevertheless, no trials assessing management for antidepressant-induced sexual dysfunction were found showing a benefit of psychological interventions, mechanical devices, or changes to antidepressant medication regimen. There is some evidence that for men with antidepressant- induced erectile dysfunction, the addition of sildenafil is of benefit in improving sexual function, while at the present, it is unclear if the addition of bupropion or buspirone is of benefit.
There are only sporadic reports of the impact of mood stabilizing agents on sexual function. Lithium carbonate resulted in reduced sexual interest and increased erectile difficulties in 20% of bipolar and schizoaffective male patients, although there was no correlation between lithium level and loss of overall satisfaction during sexual activity.
Many anticonvulsivants, such as carbamazepine and valproate, are commonly used as mood stabilizers and, as better specified in a previous chapter, they may lead to sexual dysfunction through complex and still poorly understood mechanisms.
Benzodiazepines act to increase the inhibitory process of the central nervous system primarily though γ-aminobutyric acid, a chief inhibitory neurotransmitter. Although the overall risk of SD with BDZ is relatively low, high dose BDZ therapy has been associated with an increased incidence of SD. In contrast, anxiolytics which act primarily on 5-HT1A, such as buspirone, are associated with improved sexual function.
Decreased libido is very common with the older conventional antipsychotic drugs (e.g., haloperidol, fluphenazine, and chlorpromazine), since they are potent dopamine blockers also increasing prolactin levels, with 30% to 60% of patients experiencing disturbances in sexual function . Among the newest atypical antipsychotic drugs, risperidone is most likely to cause elevations in prolactin levels and hyperprolactinemic symptoms such as gynechomastia , erectile dysfunction, and decreased libido. On the contrary, hyperprolactinemia is rarely associated with quetiapine, ziprasidone, aripriprazole, or clozapine . Moreover, risperidone has also been associated to ejaculatory dysfunction, such as retrograde ejaculation . Interestingly, because of their increased serotoninergic effects, atypical antipsychotics may cause additional adverse effects on arousal and orgasm function.