The question concerns a 20-year-old woman who has been treated with citalopram 20 mg per day, since

Fråga: The question concerns a 20-year-old woman who has been treated with citalopram 20 mg per day, since April 1995. About two weeks ago, the daily dose was increased to 30 mg. Yesterday (950711), the patient noticed galactorrhea. Other medication: contraceptives (since many years) and a single dose of 5 mg of Esucos (dixyrazin) one week ago. Could the galactorrhea be caused by citalopram?

Sammanfattning: No published reports concerning galactorrhea caused by citalopram have been found in the literature, but this adverse effect has been reported for other SSRIs, such as sertraline, fluoxetine and fluvoxamine. The increase in prolactin levels is suggested to be mainly caused by serotonergic inhibition of dopamine release from tuberoinfundibular dopamine neurons. Resolvement of galactorrhea after discontinuing the drug would certainly suggest a causal relationship with citalopram, but in this particular case, the patients´ condition may not allow a dechallenge.

Svar: Galactorrhea is known as an adverse effect of several groups of psychotropic drugs, including antipsychotics, tricyclic antidepressants and clomipramine. No published reports regarding galactorrhea caused by citalopram could be found. However, we did find some case reports concerning other so-called selective serotonin reuptake inhibitors (SSRIs).

One case report (1) concerned a 37-year-old woman who was treated with fluoxetine 20 mg/day for depression. After one week, the treatment was switched to sertraline 50 mg/day, which was increased to 100 mg/day after two weeks. Approximately five weeks after starting the sertraline treatment, the patient reported the onset of galactorrhea. The symptom ceased 21 days after discontinuing sertraline treatment. The case report did not mention a rechallenge. Another report (2) concerns two cases of breast discomfort and enlargement without galactorrhea in two women taking sertraline. In both cases the symptoms occurred six weeks after the sertraline dose had increased from 50 mg to 100 mg/day. The symptoms resolved in both cases after discontinuing the drug.

According to reference (1), the premarketing prevalence rate of galactorrhea following fluoxetine administration was 0.07 per cent. In addition, in a post-marketing follow-up a total of 204 cases of galactorrhea (in an estimated 3.4 million patients) were reported to the manufacturer.

There are also a few case reports with respect to fluvoxamine (3,4). One case concerned a 38-year-old woman who developed amenorrhea and galactorrhea after treatment with 150 mg fluvoxamine for six weeks (3). During the same period, the patient was maintained on loxapine, oxazepam and zopiclone (drugs she had used for a long time). The loxapine dose was decreased from 150 mg to 75 mg daily. The patient´s prolactin level was 80 ug/L (reference value 4-30 ug/L). The symptoms resolved within a month after fluvoxamine was discontinued. Reference (4) concerns a similar case-report of a 28-year-old woman with symptoms of galactorrhea and high prolactin levels after being treated with fluvoxamine 150 mg/day for one month. The symptoms resided after the dose was reduced to 50 mg/day.

The serotonergic regulation of prolactin release in seven estrogen-withdrawn, postmenopausal women was investigated after administration of 60 mg fluoxetine per day for 7 days (5). The mean 24-hour-serum prolactin concentrations increased significantly, from 9.6 to 11.1 ug/L, and so did the (calculated) maximal prolactin peak height and the mass of prolactin secreted per 24 hours. Prolactin pulse frequency was not affected. As estradiol has been implicated in stimulation of prolactin release, it was suggested that the prolactin response in women taking fluoxetine who are not estrogen-deficient may even be more pronounced (5). Serotonin probably does not stimulate the pituitary directly and is not a prolactin-releasing factor (PRF) itself (6). The increase is probably (partly) due to inhibition by serotonin of dopamine release from tuberoinfundibular dopamine neurons. However, other mechanisms may be involved as well, such as an activation of prolactin releasing factors by serotonin, such as GABA, TRH, VIP or neurotensin (4).

No cases of galactorrhea caused by citalopram are known to the manufacturer (7). One report concerning this side-effect has been received by the Swedish Adverse Drug Reactions Advisory Committee (SADRAC). As the present patient has only taken a single dose of Esucos, a drug that may cause galactorrhea a causal relationship with citalopram is possible. We recommend this case to be reported to SADRAC.