For how long may galactorrhea persist after discontinuation of neuroleptics?/nBackground: A 18-year

Fråga: For how long may galactorrhea persist after discontinuation of neuroleptics?

Background: A 18-year-old woman developed bilateral galactorrhea in February 1997, regarded as a side effect to treatment with perfenazine (Trilafon). Since then, she has tried several different neuroleptics with persistence of galactorrhea. Treatment with haloperidol was stopped and during the past three months she has only taken alimemazine (Theralen) twice a week and sertraline (Zoloft) 100 mg daily. In July unilateral galactorrhea still remains.

Sammanfattning: Galactorrhea has been reported as a side effect due to treatment with different neuroleptics including perphenazine as well as the selective serotonin reuptake inhibitors. If other medical causes to galactorrhea have been excluded in the present case, neuroleptics should be considered as a probable cause of the galactorrhea. However, this usually lasts only a few weeks after drug discontinuation. In the present case treatment with haloperidol was stopped three months ago, which makes haloperidol less likely as a cause to the prolonged galactorrhea. Alimemazin has not been connected with galactorrhea, but a causal-effect relationship can not be excluded during continuous therapy. However, daily treatment with sertraline 100 mg is another possible cause to the prolonged galactorrhea as described above. First, it is suggested to decrease the dose of sertraline or to try another antidepressant. Second, alimemazin treatment could be stopped, in order to eliminate the symptoms.

Svar: Galactorrhea is a well-known side effect of neuroleptics due to blockade of dopamin receptors which increase the release of prolactin, thus stimulating milk secretion (1). This side effect appears to be dose-dependent and diminishes with dose-reduction (2,3). The files of the Swedish Adverse Drug Reaction Advisory Committee (SADRAC) contain many such reports in connection with neuroleptics. In most of these cases galactorrhea lasted a few weeks, but in one case galactorrhea lasted as long as two months after drug discontinuation. Although, alimemazine has not been reported to SADRAC, it cannot be excluded that alimemazine may cause galactorrhea since this side effect is well-documented for other phenothiazines (4).

On the other hand we found three reports in SADRAC concerning galactorrhea during sertraline treatment. In one report galactorrhea ceased after lowering the daily dose from 200 mg to 150 mg. A letter describing this rare side effect of selective serotonin reuptake inhibitors was recently published (5). In that case galactorrhea developed after a dose increase from 100 mg to 150 mg daily. Sertraline was promptly discontinued and the symptoms disappeared about three weeks later(5). Instead paroxetine 20 mg/day was tried without the development of galactorrhea. Although galactorrhea associated with sertraline treatment seems to be dose-dependent, it cannot be excluded that paroxetine might also precipitate galactorrhea if the dose had been increased. The mechanism has been suggested as an elevation of prolactin level by serotonergic activation of prolactin-releasing factors such as thyrotropin-releasing hormone and gamma-aminobutyric acid, and/or mediated by serotonergic inhibition of prolactin inhibitor factors such as dopamine (5). This dopamine theory is also supported by the fact that all the SSRI´s may occasionally give rise to extrapyrimidal symptoms (6).

Galactorrhea in connection to the other SSRI´s eg citalopram, fluoxetine, fluvoxamine and paroxetine has previously been reported (7-10). The register of SADRAC contains ten more reports on galactorrhea where citalopram or paroxetine may have contributed to the symptoms. An updated Medline search revealed no new information.

We recommend this case to be reported to SADRAC. 1 Drugline nr 06122 (year 1988) 2 Drugline nr 12688 (year 1995) 3 The Swedish Adverse Drug Reactions Advisory Committee´s adverse reactions databse 4 Drugline nr 06320 (year 1988) 5 Peterson KA, Armstrong S, Moseley J: Sertraline and galactorrhea (letter). J Clin Psychopharmacol 1996; 16: 333-334 6 Avery´s, Drug Treatment, 1997; 4th ed: 1425 7 Drugline nr 13248 (year 1997) 8 Drugline nr 13126 (year 1996) 9 Drugline nr 13501 (year 1996) 10 Drugline nr 12137 (year 1995)