Canadian Tablets: Psychotropic and central nervous system drugs
Psychotropic and central nervous system drugs
Phenothiazines
Thioridazine
This neuroleptic used in the treatment of schizophrenia is well known for its sexual side effects at doses as low as 30 mg/day. In men, thioridazine was first reported to interfere with ejaculation in 1961. Since then numerous case reports and a few studies describe decreased libido, difficulty achieving and maintaining erections and inability to achieve orgasm. The drug has even been used therapeutically in an attempt to treat hypersexuality and premature ejaculation. 
Kotin and colleagues performed a large study investigating thioridazineinduced sexual dysfunction in sexually active schizophrenics. Thioridazine produced some form of sexual dysfunction in 60% of patients; 44% of thioridazine-treated patients developed difficulties achieving erection compared with 19% in patients treated with other major tranquilisers. In addition, 35% of thioridazine patients had difficulty in maintaining erection (controls 11%). Half of the thioridazine group noted changes in ejaculation, whilst this was not noted in any controls. The majority of the 28 patients with altered ejaculation had no ejaculate at orgasm, the remainder reported reduced ejaculate volume. No tests were performed to see if these men had retrograde ejaculation, but this phenomenon has been previously suggested in thioridazine-treated patients. Only one report, however, has given even indirect evidence for retrograde ejaculation; a single patient complained of passing ‘white urine’ following orgasm without ejaculation. Two men in the series described by Kotin and co-workers (1976) also reported pain on orgasm and one of the authors who voluntarily took a test dose of the drug and masturbated 4 hours later described a tearing suprapubic pain at orgasm, but no ejaculate was produced.
Several cases of priapism have also been described. This is thought to be related to a-adrenergic blockade. One study showed that serum levels of testosterone and LH are lower in patients on thioridazine than in controls.
In women, thioridazine has been reported to be associated with orgasmic dysfunction. An early study reported that amenorrhoea occurred in up to 50% of patients, but this effect is reversible and normal menstruation returned after discontinuation of thioridazine. The datasheet also mentions hyperprolactinaemia resulting in galactorrhoea, oligomenorrhoea and amenorrhoea.
Chlorpromazine
Chlorpromazine is a widely used neuroleptic. Clinically, there is little evidence of sexual dysfunction with chlorpromazine. At 125mg/day, chlorpromazine has no more sexual side-effects than placebo. However, a case of ejaculatory failure has been reported at 1200mg/day, as well as decreased libido and decreased erectile ability. Libido, erection and orgasm returned at 400 mg/day (
Buffum, 1982). Several cases of priapism have been reported at doses of 100 mg/day and above (Buffum, 1986). In one unusual case, priapism developed after a patient inserted a crushed chlorpromazine tablet into the urethral meatus of his penis. One man developed priapism 5 days after a single 200 mg intramuscular dose.
Priapism is usually thought to be caused by a-adrenergic blockade but the authors of this case report argued that it may also represent a hypersensitivity reaction. Other mechanisms suggested include dopamine blockade leading to spasm of the ischiocavernous muscles and compression of the corpora cavernosa. The effects of chlorpromazine on sexual function usually appear to be reversible and dose related.
Fluphenazine
Fluphenazine has been used specifically for its libido-reducing properties in sexual offenders, although paradoxically two cases of hypersexuality were reported in males treated with 12.5 mg fluphenazine decanoate every 3 weeks. 
Reduction in sexuality was found in 65 to 75% of both deviant and normal males at doses of 25 mg/day. In a study including schizophrenic patients treated with fluphenazine, 54% of male patients reported sexual dysfunction, including erectile dysfunction and anorgasmia. Decreased quantity of ejaculate was noted in 46%. In the same study, 30% of females reported abnormal sexual function mainly related to orgasmic difficulties. One study looked at hormone levels in 24 male schizophrenic patients on long-term fluphenazine treatment. Two thirds had decreased libido or erectile difficulties. The prolactin levels were two to four times greater in treated patients compared with untreated healthy controls. The prolactin concentration in impotent patients tended to be higher than the nonimpotent group, but the difference was not statistically significant. Priapism has also been described as a complication of fluphenazine.
Perphenazine
Perphenazine caused interference with emission and ejaculation in 64% of a group of 14 patients. In some patients the effects lasted for several months after discontinuation of treatment. 
Other antipsychotics
Haloperidol. Haloperidol belongs to the butyrophenone group and as it does not produce the autonomic effects of phenothiazines it rarely produces sexual dysfunction. One case of pain on ejaculation has been reported (Berger, 1979) as has a case of impotence.
Flupenthixol. A case report describes a 30-year-old schizophrenic who had experienced inability to ejaculate for several years on various neuroleptics and was latterly taking flupenthixol. This inability was reversed within a few days by the administration of cyproheptadine.
Pimozide. Pimozide is a neuroleptic belonging to the diphenylbutylpiperidine group. It is a selective dopamine antagonist and is known to be less sedating than other compounds. A case of impotence and ejaculatory inhibition was reported at 12 to 16 mg/day.
Trifluoperazine. Reports of interference with emission and ejaculation were shown in one early study of five patients. Another study showed no adverse effects on ejaculation. Delayed female orgasm has been recorded.
Sulpiride. Sulpiride is a substituted benzamide that interacts with dopamine receptors. One study investigated prolactin levels in two groups of patients treated with sulpiride. Patients with anxiety disorders were treated with doses up to 200 mg per day and schizophrenic patients up to 600 mg per day. Patients on higher doses had higher prolactin levels. Four of the six patients taking 600 mg per day developed impotence compared with one of seven patients on the lower dose. Restoration of potency was observed after reduction or discontinuation of treatment. This study strongly suggests that in this group of patients the sexual side effect of the neuroleptic was related to hyperprolactinaemia.
Remoxipride. Remoxipride is a new molecule also belonging to the substituted benzamide group. It is selective for central dopaminergic receptors. No published reports of effects on sexual activity are available Risperidone.
Risperidone is a new antipsychotic, belonging to the benzisoxazole derivatives. Erectile, ejaculatory and orgasmic dysfunction are all mentioned in the data sheet as side effects. Clozapine. At least three recent case reports have described priapism as a complication of the new atypical antipsychotic agent clozapine.
Others. Butaperazine, chlorprothixene, mesoridazine and thiothixene have also been noted for causing sexual dysfunction. These drugs are not licensed in the UK.
