Men's Health Education: The Effects of Commonly Used Antipsychotic Drugs (Phenothiazines) on Sexual Function

Antipsychotic Drugs

This class of drugs, formerly known as "maiortranquilizers" or "neuroleptics," is also called "antipsychotic drugs" because it is primarily used clinically to treat schizophrenia. It is also effective against mania.

Antipsychotic drugs are mainly used to control schizophrenia. Although these drugs have been recognized as essential medications for treating acute and chronic schizophrenia, they are not effective in correcting the underlying mental abnormalities. Antipsychotic drugs can reduce symptoms such as agitation, hostility, aggression, hyperactivity, thought and perception disturbances, depressed mood, and paranoid behavior. Most of these drugs can reduce seizures and psychomotor activity, and can also affect the regulation of extrapyramidal function.

1. Phenothiazines
Phenothiazines are a class of compounds consisting of two benzene rings linked by sulfur and nitrogen atoms. Based on their side chains, phosphodiesterase inhibitors (PSIs) can be further divided into dimethylamines (such as chlorpromazine), piperazines (such as perphenazine, fluphenazine, and trifluoperazine), and piperidines (such as thioridazine).

①Chlorpromazine
Chlorpromazine is a representative drug of the phenothiazine class and is the most widely used in clinical practice. Chlorpromazine has as many as 50 chemical and trade names, the most commonly used being: Wintermin, chlorpromazine, clonidine, largactil, aminazine, thorazine, RP4560, CPZ, etc.

Clinically, chlorpromazine is mainly used to treat various types of schizophrenia. It is effective for acute cases, but it does not cure the condition; long-term use is necessary to maintain efficacy and reduce relapse. In addition, chlorpromazine can also be used to treat mania and other psychoses accompanied by agitation, tension, and delusions.

The mechanism of action of chlorpromazine in treating psychosis is currently believed to be through blocking dopamine (DA) receptors in the mesolimbic system and mesocortical pathway, thereby exerting its antipsychotic effect. Blocking DA receptors in the substantia nigra-striatal pathway is the cause of extrapyramidal reactions.

Chlorpromazine has a significant α-receptor blocking effect, reversing the pressor effect of adrenaline. It also inhibits the vasomotor center and directly inhibits vascular smooth muscle, thus dilating blood vessels and lowering blood pressure. Therefore, high doses in psychotic patients can cause orthostatic hypotension. Chlorpromazine has a strong adrenergic blocking effect (α-receptor blocking) and a weaker cholinergic blocking effect (M-receptor blocking). It also has endocrine activity; by acting on the hypothalamus, it increases prolactin levels in the bloodstream and inhibits gonadotropin secretion. Analyzing the various mechanisms by which drugs cause sexual dysfunction, the aforementioned effects can lead to various clinical manifestations of sexual dysfunction in patients taking these medications. Clinical observations have confirmed this; for example, the drug can prevent ovulation, cause menstrual irregularities, induce galactorrhea (approximately 1%–2%), gynecomastia in men (approximately 0.9%, related to dosage and duration of use, such as >300mg, daily dose, more than 20 days, etc.), and testicular atrophy. Decreased libido is common, occurring in approximately 10%–20% of cases, perhaps reflecting the sedative effect of these drugs, or the occurrence of other sexual dysfunctions such as impotence may be related to drug dosage.

Phenothiazine antipsychotics, represented by chlorpromazine, are similar to most other antipsychotics in that they readily cause sexual dysfunction in patients at therapeutic doses. The mechanism by which chlorpromazine causes sexual dysfunction is mainly related to its central inhibitory effects, antihistamine effects, α-receptor blocking effects, inhibition of testosterone levels, and significant increase in PRL levels.

② Thioridazine (also known as thioridazine, thioridazine, Mallorol, Malloryl) belongs to the phenothiazine class, the same as chlorpromazine, but differs from chlorpromazine by having a piperidine alkyl group at the 10-position of its tricyclic structure. Thioridazine was the first antipsychotic drug reported to cause impotence or erectile dysfunction. Kotin et al. investigated 87 psychiatric patients and found that 60% of those taking thioridazine experienced sexual dysfunction, compared to 25% of those taking other antipsychotic drugs. Furthermore, among patients taking this medication, the incidence of impotence and erectile dysfunction (priapism) was 44% and 35%, respectively; while among patients taking other antipsychotics, the incidence of these disorders was 19% and 11%, respectively. Some reports indicate that impotence can occur with a daily dose of 20 mg of thioridazine, often occurring early in the course of treatment (e.g., within 24 hours).

③ Other phenothiazine drugs

Perphenazine, fluphenazine, and trifluoperazine are all piperazine derivatives of the phenothiazine class. They share the characteristics of strong antipsychotic effects, significant extrapyramidal side effects, and relatively weak sedative effects. Fluphenazine and trifluoperazine are the most commonly used and have better efficacy; perphenazine is less effective. Their antihypertensive effects are weaker than those of chlorpromazine and thioridazine. The usual antipsychotic dosages are: fluphenazine 2.5–20 mg/day; trifluoperazine 6–20 mg/day; and fluphenazine 8–32 mg/day.

These three drugs all have varying degrees of impact on sexual function. For example, fluphenazine can cause impotence. Blair and Simpson studied the effects of antipsychotic drugs, including fluphenazine, trifluoperazine, and butaperazine, on ejaculation in 35 patients with chronic schizophrenia. They found that ejaculation volume was affected to varying degrees after treatment compared to before treatment, and the ejaculatory dysfunction was intermittent and transient. There is no necessary causal relationship with drug dosage, as the reported drug dosages are all within the normal therapeutic range. Trifluoperazine can also cause sexual pleasure disturbances. During the use of antipsychotic drugs, libido is often reduced, partly due to their central inhibitory effects.

2.Butyrophenones

Butyrophenones have a completely different chemical structure from phenothiazines, but their effects are basically similar. Haloperidol is a representative drug in this class.

Haloperidol

Haloperidol, also known as haloperidol, haloperidol, haloperidol, Serenelfi, Serenace, Aloperidin, Aldol, Halol Vesalium, Pernox, R-1625, etc., has a similar mechanism of action to phenothiazines and can also block DA receptors. It is characterized by its strong antipsychotic effect; for example, if the oral equivalent dose of chlorpromazine is 100mg, then haloperidol is 2mg, almost 50 times stronger (equivalent to fluphenazine), and very similar to phenothiazine derivatives (such as fluphenazine). It also has a significant impact on sexual function. Because this drug can also block dopamine (DA) in the central nervous system, it can increase prolactin (PRL), and common side effects include galactorrhea and gynecomastia (male-female breast development). 10%–20% of men taking this drug experience impotence; female patients may experience menstrual irregularities. Interestingly, small doses of haloperidol can increase testosterone production, but large doses can inhibit testosterone production. There are also reports of it causing sexual dysfunction, decreased libido, and other sexual problems. Reducing anxiety generally enhances sexual function, while the sedative effect usually reduces sexual response and libido.