Neuroleptic drugs prolactin

Dopamine A few studies have examined the dopaminergic effects of LSD. The affinity of LSD for D2 receptors is similar to its affinity for 5-HT2 sites, and it has a slightly lower affininty for D1 receptors (Watts et al. 1995). LSD has partial agonist effects at D2 receptors as seen in the inhibition of prolactin release (Giacomelli et al. 1998). Neuroleptic drugs are also used clinically to terminate an LSD experience. Thus, the effects of LSD on dopaminergic function may contribute to its hallucinogeinc effects. 

Neuroendocrine effects of neuroleptic drugs include a rise in growth hormone, inappropriate ADH and prolactin secretion, and disturbances of sex hormones (SEDA-7, 67). Galactorrhea (SEDA-20, 43) and gynecomastia can follow the rise in prolactin. 

A correlation between serum concentrations of neuroleptic drugs and prolactin has been claimed (746,747). In 55 patients who had been taking neuroleptic drugs for more than 10 years, higher doses of medication were associated with increased rates of both hyperprolactinemia and bone mineral density loss, as shown by dual X-ray absorptiometry of their lumbar and hip bones (748). 

There is concern that neuroleptic drugs may increase the risk of breast cancer because of raised prolactin concentrations. For a long time, findings did not confirm this association (752), but a Danish cohort study of 6152 patients showed a slight increase in the risk of breast cancer among schizophrenic women (753). 

In eight patients receiving neuroleptic drugs, serum prolactin concentrations were grossly raised (754). The... 

Some patients who take clozapine take another neuroleptic drug, and the consequences of this practice in terms of prolactin have been studied in five patients (758). After the addition of haloperidol (4 mg/day) to clozapine the mean prolactin concentration increased from 9.7 ng/ml to 16 ng/ml at week 4 and 19 ng/ml at week 6. Each subject had an increase in the percentage of D2 receptor occupancy, and the group mean increased from 55% at baseline to 79% at week 4 the increased prolactin concentrations correlated with receptor occupancy. 

There was a significant rise in baseline serum prolactin concentration in 10 patients after they had taken risperidone for a mean of 12 weeks compared with 10 patients who were tested after a neuroleptic drug-free wash-out period of at least 2 weeks (1014). A non-significant increase in serum prolactin has also been observed in an open comparison of risperidone with other neuroleptic drugs in 28 patients (1015). However, in a meta-analysis of two independent studies (n = 404), prolactin was greatly increased by risperidone (mean change 45-80 ng/ml), a larger effect than with olanzapine and haloperidol (1016). 

The authors suggested that men with primary hypothyroidism may be particularly sensitive to neuroleptic drug-induced increases in prolactin concentrations. 

Pollock A, McLaren EH. Serum prolactin concentration in patients taking neuroleptic drugs. Clin Endocrinol (Oxf) 1998 49(4) 513-6. 

Since neuroleptic drugs raise prolactin concentrations, there is concern that this may increase the risk of breast cancer. Although studies have failed to show an association, it would be best to avoid neuroleptic drugs in a patient with a hormone-dependent breast tumor. 

A correlation between serum concentrations of neuroleptic drugs and prolactin has been claimed (421,422). 

In eight patients receiving neuroleptic drugs, serum prolactin concentrations were grossly raised (428). The time-course of the prolactin increase was examined in 17 subjects whose prolactin concentrations rose during the first 6-9 days of treatment with haloperidol (429). The increase was followed by a plateau that persisted, with minor fluctuations, throughout the 18 days of observation. 

Patients whose prolactin concentrations increased above 77 ng/ml (n = 2) had hypothyroidism, and it is known that TRH (thyrotropin) stimulates the release of prolactin (430). It was concluded that all patients should have had TSH determinations at the start of therapy with neuroleptic drugs. 

Estrogen-containing formulations can further promote neuroleptic drug-induced prolactin stimulation (623). 

The mechanisms of weight gain are not known. Olanzapine, for example, affects at least 19 different receptor sites, may have reuptake inhibition properties, and may affect hormones such as prolactin. Animal models do not help to elucidate mechanisms, since they have not shown clear results some studies have shown weight gain with neuroleptic drugs in rats and others have not. 

The effects of neuroleptic drugs on fertility are not clear many of the data are controversial, often being based on animal studies, for example reduction in male rat copulation by chlorpromazine. However, oligospermia, polyspermia, necrospermia, and reduced sperm motility have been reported with various phenothiazines and butyro-phenones these are likely to improve after withdrawal (473). Furthermore, fertility may be impaired by neuroleptic drugs, since they increase prolactin concentrations and can cause amenorrhea (4). 

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