Psychotropics and Male Reproduction

Psychotropic drugs, including antidepressants, antipsychotics, and anticonvulsants, all have negative effects on sexual function and semen quality. These adverse events vary among men and are less pronounced for some medications, allowing their effects to be managed to some extent. Use of specific serotonin reuptake inhibitors (SSRIs) is prevalent in men of reproductive age; and application to treat premature ejaculation increases the number of young men on SSRI therapy. Oxidative damage to sperm can result from prolonged residence in the male reproductive tract. The increase in ejaculatory latency seen with SSRIs likely underlies some of their negative effects on semen quality, including higher sperm DNA fragmentation, seen in all SSRIs evaluated thus far. These medications increase prolactin (PRL) levels in some men, and this is often credited with inhibitory effects on male reproduction; however, testosterone levels are generally normal, reducing the likelihood of direct HPG axis inhibition by PRL. The tricyclic antidepressants have also been shown to increase PRL levels in some studies but not in others. The exception is the tricyclic antidepressant clomipramine, which profoundly increases PRL levels and may depress semen quality. Other antidepressants modulating synaptic levels of serotonin, norepinephrine, and/or dopamine may have toxicity similar to SSRIs, but most have not been evaluated. In limited studies, norepinephrine-dopamine reuptake inhibitors (NDRIs) and serotonin agonist/reuptake inhibitors (SARIs) have had minimal effects on PRL levels and on sexual side effects. Antipsychotic medications increase PRL, decrease testosterone, and increase sexual side effects, including ejaculatory dysfunction. The greatest evidence is for chlorpromazine, haloperidol, reserpine, risperidone, and thioridazine, with less effects seen with aripiprazole and clozapine. Remarkably few studies have looked at antipsychotic effects on semen quality, and this is an important knowledge gap in reproductive pharmacology. Lithium increases PRL and LH levels and decreases testosterone although this is informed by few studies. The anticonvulsants, many used for other indications, generally decrease free or bioavailable testosterone with variable effects on the other reproductive hormones. Valproate, carbamazepine, oxcarbazepine, and levetiracetam decrease semen quality; other anticonvulsants have not been investigated for this adverse reaction. Studies are required evaluating endpoints of pregnancy and offspring health for psychotropic medications.