Antipsychotics

Dopamine is a physiological inhibitor of prolactin secretion; antagonism of the D₂ dopamine receptor by antipsychotics can therefore increase circulating prolactin and in some cases cause hyperprolactinaemia.

Left undiagnosed, raised prolactin concentration can have serious consequences, which can affect men as well as women. Excessive prolactin can cause menstrual disturbances including amenorrhoea, reduced fertility, galactorrhoea, gynaecomastia, breast pain, sexual adverse effects such as loss of libido and erectile dysfunction, and, over the long term, reduced bone mineral density and osteoporosis.

Antipsychotics vary in their risk for elevating prolactin—for example, butyrophenones (eg haloperidol), phenothiazines (eg chlorpromazine and trifluoperazine), amisulpride, and risperidone are associated with higher risk of raising prolactin, but the risk is much smaller with aripiprazole and clozapine.

Factors which increase risk

Women of child-bearing age may be at greater risk of hyperprolactinaemia than those who are post-menopausal.

Raised concentration of prolactin before starting antipsychotic treatment or the existence of prolactin-dependent tumours increases the risk of prolactin-induced harm.

Risk-reduction measures

Antipsychotics which raise prolactin concentration should not be used in those with prolactin-dependent tumours.

In addition to measuring prolactin concentration, the patient should be monitored for features of hyperprolactinaemia. As part of medication review, compassionate and frank enquiry about sexual adverse events should be included, for men and women. Patients should be asked about galactorrhoea and gynaecomastia since they may be reluctant to raise these sorts of problems.

Antipsychotic treatment should be chosen carefully for those at higher risk of osteoporosis (eg alcoholism, anorexia nervosa, smoking, immobility, corticosteroid¹ use, menopause).

Treatment

In patients who develop hyperprolactinaemia, treatment should be switched to a drug that does not increase prolactin concentration. Reversal of hyperprolactinaemia will affect fertility and it may be necessary to review contraceptive arrangements.

For difficult cases, specialist advice is needed and in some cases it may be necessary to add drugs that decrease prolactin concentration.

This learning module discusses noteworthy risks for antipsychotics. Summaries of product characteristics and the BNF should be consulted for a fuller account of the adverse effects and warnings for individual antipsychotics.