Prolactin and antipsychotic medications: mechanism of action.
Until the introduction of the first atypical antipsychotic, clozapine, in 1975, hyperprolactinemia was assumed to be an inevitable consequence of treatment with any antipsychotic agent. Now we know that atypical antipsychotics such as clozapine, olanzapine, quetiapine, sertindole, and ziprasidone are not associated with significant prolactin increase. These new antipsychotics appear to spare dopamine blockade within the brain's tubero-infundibular tract, a dopamine pathway that also controls prolactin secretion. Since the release of prolactin is tonically inhibited by the hypothalamus, with dopamine acting as the prolactin release-inhibiting factor, any disruption of the connection between the hypothalamus and the pituitary gland is associated with hyperprolactinemia. Other factors that can increase prolactin secretion are also reviewed (e.g. estrogens, thyroid-releasing factor, vasoactive intestinal peptides, opioids, surgery, illness such as epilepsy or herpes zoster infection, and psychic or physical stress). Prolactin levels are at their highest 1-2 hours before waking, and early waking interrupts its secretion. The major effects of hyperprolactinemia in women are amenorrhea, cessation of normal cyclic ovarian function, loss of libido, occasional hirsutism, and increased long-term risk of osteoporosis. The effects in men are impotence, loss of libido, and hypospermatogenesis. Current data indicate that conventional antipsychotics, as well as high doses of risperidone (> 6 mg/day), increase prolactin levels to a range associated with sexual dysfunction in nonpsychiatric patients. The lack of prolactin elevation reported with the atypical antipsychotics is believed to be due to their much greater specificity, which results in less blockade of dopamine receptors in the tubero-infundibular pathway.
Petty
R G
RG
University of Pennsylvania, Department of Psychiatry, Philadelphia, PA 19104-4283, USA. petty@bblmail.psycha.upenn.edu
D000568:Amenorrhea / Q000209:etiology; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000139:chemically induced* / Q000150:complications; D008297:Male; D011388:Prolactin / Q000502:physiology*; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced
D014150:Antipsychotic Agents; D004967:Estrogens; D011388:Prolactin; D004298:Dopamine