Can alprazolam cause hyperprolactinemia?/nAn isolated hyperprolactinemia is being investigated in a

Fråga: Can alprazolam cause hyperprolactinemia?

An isolated hyperprolactinemia is being investigated in a woman treated with alprazolam (Xanor) and possibly an analgesic agent (unspecified).

Sammanfattning: Benzodiazepines can cause hyperprolactinemia, although the mechanism is poorly understood. There are a few published cases where patients treated with alprazolam developed this condition. Furthermore, a single dose of alprazolam doubled serum prolactin levels 2-8 hours after administration in healthy subjects.

Notably, opiates could also increase prolactin levels, wherefore the nature of the patient´s analgesic might be of interest.

Svar: Several drugs can cause elevated prolactin levels. The mechanisms include hypothalamic dopamine depletion (reserpine, methyldopa), dopamine receptor antagonism (neuroleptics), serotonin reuptake inhibition (antidepressants), histamine receptor antagonism (cimetidine, ranitidine) and direct stimulatory effects on the pituitary prolactin-producing cells (opiates) (1,2). For other drug classes, such as benzodiazepines, the mechanisms involved are unknown (1). Typically, the prolactin level is normalised within a few weeks following withdrawal of the causing drug (3).

In Drugline, a case of hyperprolactinemia during alprazolam treatment is described. The woman in question was also treated with citalopram and tramadol (4).

In Swedis, there are no reports of alprazolam-induced prolactin elevations (5). The WHO adverse drug reactions´ database contains twenty such reports. It should be noted, though, that the causal relationship to alprazolam treatment has not been evaluated in some of these reports (6).

In Medline, two publications addressing the subject were identified. The first of these described two women who developed symptomatic hyperprolactinemia during treatment with alprazolam 2.4 and 3.2 mg/d, respectively. The prolactin levels were approximately 2-4 times the upper limit of the normal range, and were normalised following dose reduction to 0.8 and 2.4 mg/d, respectively (7).

In the second study, ten healthy males were given a single dose of 3 mg alprazolam or placebo in a cross-over fashion. As compared to placebo, alprazolam caused a statistically significant 100 percent increase in prolactin levels 2-8 hours after administration (8). 1 Lee A, editor. Adverse drug reactions. London: Pharmaceutical Press; 2001. p. 129-30. 2 Brody S, Obstetrik och gynekologi. Klinisk praxis och teoretisk bakgrund. 9th ed. Falköping: Almqvist & Wiksell; 1993. p. 612. 3 Davies DM, Ferner RE, de Glanville H, editors. Davie´s textbook of adverse drug reactions. 5th ed. Philadelphia: Lippincott-Raven Publishers; 1998. p. 393-4

4 Drugline no 14432 (year 1997)
5 Swedis (The Swedish Drug Information System) (cited 2003-06-05)
6 Vigibase: WHO:s adverse drug reactions database (cited 2003-06-05)

7 Shioiri T, Kita N, Takahashi S. Two cases of alprazolam-unduced hyperprolactinemia in patients with panic disorder. Int Clin Psychopharmacol 1996;11:149-52. 8 Zemishlany Z, McQueeney R, Gabriel SM, Davidson M. Neuroendocrine and monoaminergic responses to acute administration of alprazolam in normal subjects. Neuropsychobiology 1990;23:124-8.