Are there any differences between antidepressants with regard to their liability to cause hyperprol

Fråga: Are there any differences between antidepressants with regard to their liability to cause hyperprolactinemia?

Sammanfattning: Selective serotonin reuptake inhibitors are probably more liable to cause prolactin elevation compared to other classes of antidepressants. Theoretically, the risk should be lower with predominantly noradrenergic drugs such as reboxetine and mirtazapine, although there are indications that these drugs may also have some influence on prolactin secretion.

Svar: Drug-induced hyperprolactinemia usually involve inhibition of dopaminergic neurotransmission (predominantly neuroleptics) or interference with serotonin re-uptake or the sensitivity of postsynaptic serotonin receptors (1). Hence, it is not surprising that hyperprolactinemia is more common in treatment with selective serotonin reuptake inhibitors (SSRI:s) than with tricyclics and monoamino-oxidase inhibitors with less serotonergic profiles (2). The frequency of hyperprolactinemia in SSRI-treated patients is not well defined, though. In the Swedish catalogue of approved medical products (FASS), it is mentioned as a side-effect of only two SSRI:s (paroxetin and sertralin), supposedly occurring at a frequency of less than 1 per 1000 treated patients (3). However, in several studies where prolactin levels have been monitored, treatment with various SSRI:s have uniformly brought about some degree of prolactin elevation (4).

Amongst the SSRI:s, sertraline has the strongest antagonistic effect on dopamine reuptake, and this could theoretically counteract its serotonin-mediated prolactin-stimulating effects. This notion is supported by very low reported frequencies of amenorrhea and galactorrhea in patients treated with sertraline, compared to other SSRI:s. However, there are no studies directly comparing different SSRI:s in this regard. (5)

Theoretically, predominantly noradrenergic antidepressants such as reboxetine, mirtazapine and maprotiline could be less prone to cause hyperprolactinemia. However, animal studies suggest that noradrenergic neurotransmission may be of some importance in the regulation of prolactin secretion and in healthy males, reboxetine caused an acute increase in prolactin levels compared to placebo (6). Furthermore, galactorrhea is a known albeit rare side effect of maprotiline (7), and there is at least one case report of gynecomastia and galactorrhea in a mirtazapine-treated patient (8), indicating that these noradrenergic drugs may not be completely devoid of effects on prolactin secretion. Lee A, editor. Adverse drug reactions. London: Pharmaceutical Press; 2001. p. 129. Drugline no 17131 (year 1999) Fass 2005. Stockholm: Läkemedelsindustriföreningen, LIF; 2005 (The Swedish catalogue of approved medical products) Emiliano AB, Fudge JL. From galactorrhea to osteopenia: rethinking serotonin-prolactin interactions. Neuropsychopharmacol 2004;29:833-46. Goodnick PJ, Chaudry T, Artadi J, Arcey S. Women´s issues in mood disorders. Exp Opin Pharmacother 2000;1(5):903-16. Schule C, Bhagai T, Schmidbauer S, Bidlingmaier M, Strasburger CJ, Laakmann G. Reboxetine acutely stimulates cortisol, ACTH, growth hormone and prolactin secretion in healthy male subjects. Psychoneuroendocrinol 2004;29:184-200. Ludiomil. Summary of product characteristics (SPC) (Novartis) Lynch A, Madjlessi A. Gynecomastia-galactorrhea during treatment with mirtazapine. Presse Med 2004;33(7):458. (abstract)