Prescribing to preserve or restore sexual function
Side effects associated with psychotropics, and treatments shown to alleviate them
SSRIs have been associated with ED and ejaculatory disturbances. A high serotonin-to-dopamine reuptake inhibition ratio associated with these agents may contribute to ED. Paroxetine has a higher serotonin-to-dopamine reuptake inhibition ratio—and is associated with a higher incidence of sexual dysfunction—than other SSRIs.7
Elevated central serotonin concentrations associated with SSRIs may also inhibit orgasm. SSRIs have been used to prolong orgasm in patients experiencing premature ejaculation.8
Venlafaxine, a serotonin/norepinephrine reuptake inhibitor, exhibits similar effects on sexual function as SSRIs, probably via the same serotonin/dopamine reuptake mechanisms. The lowest effective dosage can still cause sexual dysfunction but may reduce the likelihood.
TCAs. Tricyclic antidepressants may have fewer effects on sexual function than SSRIs. The mechanisms by which TCAs decrease libido and cause ED seem to be mediated through their CNS sedative and local anticholinergic effects.
MAOIs. Monoamine oxidase inhibitors have fewer effects on sexual function than SSRIs or TCAs, but these agents are rarely used to treat depression because of their adverse effects and drug-drug interactions.
Other antidepressants. Trazodone and nefazodone exhibit similar mechanisms of antidepressant action as SSRIs, but neither agent causes significant ED or ejaculatory disturbances. Priapism has been described with use of these agents, however.
Avoid using nefazodone in patients with hepatic dysfunction and in those who have taken an MAOI within 14 days.
Mirtazapine, a novel antidepressant with antiserotonergic actions, and bupropion, a dopamine and norepinephrine reuptake inhibitor, are not associated with significant sexual dysfunction compared with placebo. These agents are good alternatives to SSRIs9-11 and may alleviate sexual dysfunction when used to augment SSRIs.12,13
Lithium has been shown to decrease libido and cause ED. Lithium-mediated CNS sedation contributes to decreased libido; other mechanisms of lithium’s sexual side effects are not known. It is unclear whether lower dosages reduce the likelihood of sexual dysfunction.
Anticonvulsants. In two small studies, phenytoin increased sex hormone-binding globulin, resulting in lower free testosterone levels, which may lead to sexual dysfunction.18,19 Barbiturates have been shown to decrease libido, probably because of CNS sedation. Carbamazepine and gabapentin exhibit antiandrogenic effects, leading to various types of sexual dysfunction. These effects have not been observed with oxcarbazepine, however.
Lamotrigine may be an effective alternative in patients exhibiting sexual dysfunction with gabapentin.20
Typical antipsychotics can impair all aspects of sexual function:14
- CNS sedation and hyperprolactinemia account for decreased libido.
- Local anticholinergic effects may cause ED. Thus, the greater the anticholinergic effects, the presumably higher the incidence of ED.
- Alpha-receptor blockade and inhibition of inner urethral sphincter closure may cause retarded and retrograde ejaculation, respectively.
Of the conventional antipsychotics, thioridazine is associated with the highest incidence of sexual dysfunction.15
Table 3
Side effects, drug interactions associated with PDE-5 inhibitors
| Drug | Adverse effects | Drug interactions |
|---|---|---|
| Sildenafil | Dyspepsia, flushing, headache, hypotension, myocardial infarction (rare), nasal congestion, rash, visual disturbances | CYP-2C9 inducers and inhibitors (minor alterations in sildenafil plasma concentration) CYP-3A4 inducers and inhibitors (major alterations in sildenafil plasma concentration) Dihydrocodeine (rare priapism) Nitrates (severe hypotension) |
| Tadalafil* | Headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, pain in limb, visual disturbances | CYP-3A4 inhibitors (increase tadalafil exposure) Alpha blockers other than tamsulosin (hypotension) Nitrates (severe hypotension) |
| Vardenafil* | Dizziness, dyspepsia, headache, hypotension | CYP-3A4 inducers and inhibitors (altered vardenafil plasma concentration) Nitrates (severe hypotension) |
| * Tadalafil and vardenafil are still undergoing post-marketing surveillance. This explains in part why fewer adverse effects and drug-drug interactions have been reported with these agents than with sildenafil. | ||
Atypical antipsychotics exhibit fewer adverse effects on sexual function than their typical counterparts, but the mechanisms that mediate these effects are the same.
Of these agents, risperidone causes the greatest prolactin elevation.16 Aripiprazole may also be associated with minimal sexual dysfunction.17 Other atypicals decrease prolactin levels or raise them transiently,16,17 so consider switching to one of these agents if a patient experiences ED.
Anxiolytics. Benzodiazepines, with their CNS sedative effects, are associated with decreased libido. Their potential for abuse may augment this effect. Buspirone, a novel anxiolytic that exhibits serotonergic and dopaminergic effects, is not associated with significant sexual dysfunction and may be a viable alternative.
Others. Amphetamines can increase the local sympathetic-to-parasympathetic activity ratio, resulting in ED. This effect is more pronounced with long-term use, though it is also seen with short-term use.
ED also has been reported in patients taking disulfiram, though it is unclear whether the drug or long-term alcohol use caused the dysfunction.
Drug treatment of ED
Because primary ED is a quality-of-life issue and not a health risk, few comparative trials have tested medications that improve erectile function. Thus, ED drug treatment may require trials of two or more agents.
Adverse effects and drug-drug interactions of selected agents used for ED treatment are listed in Tables 3 and 4.
