Probable Galactorrhea Associated with Sequential Trials of Escitalopram and Duloxetine in an Adolescent Female

To the Editor:

Medication-induced galactorrhea is typically accompanied by elevated prolactin concentrations. Prolactin concentrations in women are generally considered normal when <28.3 μg/L; however, antipsychotic drugs have caused galactorrhea at values as low as 25 μg/L (Grigg et al. 2017). As a limited number of reports describe galactorrhea in patients treated with escitalopram or duloxetine, we describe the first cases in an adolescent.

A 16-year-old female was admitted for inpatient hospitalization for depression and multiple suicide attempts. The patient had no medical comorbidities, symptoms of Cushing's disease, or excess of growth hormone. She previously experienced spontaneous galactorrhea with risperidone, leading to wetting of her underwear, which remitted after discontinuation. Two weeks before hospital admission, the patient was started on escitalopram 10 mg daily. On hospital day 2, the patient reported small amounts of milky discharge, approximately the size of a pinhead, on expression of the right nipple that had begun within the past 2 weeks. Breast examination was unremarkable, urine pregnancy screening was negative, thyroid-stimulating hormone was 1.64 mIU/L, serum creatinine was 0.76 mmol/L, and morning prolactin concentration was 29.8 μg/L. Brain imaging was not performed as the prolactin concentration was only slightly elevated. Escitalopram was discontinued and galactorrhea subsided after 2 days. Eight days after escitalopram discontinuation, duloxetine was initiated at 20 mg daily, which was titrated to 40 mg daily after 5 days. Two days after the dosage increase, the patient again reported pinhead-sized right-sided nipple discharge on expression. Upon this discovery, the duloxetine dose was reduced to 20 mg daily. A prolactin concentration was drawn the next morning and returned at 26.0 μg/L. After 5 days of the lower dose of duloxetine, the galactorrhea resolved and the patient was discharged on this dose.

In general, galactorrhea is associated with elevated prolactin concentrations, but a limited number of reports describe antidepressant-related galactorrhea with euprolactinemia. Most recently, a 24-year-old female taking escitalopram 10 mg daily reported bilateral swelling and tenderness in breasts accompanied by white milky discharge after 1 month of treatment. All laboratory results and imaging were determined to be within normal limits. Escitalopram was discontinued and galactorrhea resolved over 3 months (Pathania et al. 2018). In addition, a 28-year-old female taking duloxetine 30 mg daily experienced bilateral galactorrhea after 10 weeks of treatment. All possible medical causes were ruled out and the patient's prolactin concentration was 8.05 μg/L. Three days after duloxetine discontinuation, the galactorrhea resolved (Demirci et al. 2015).

Galactorrhea with mildly elevated prolactin occurred in our patient after treatment with escitalopram and duloxetine. The exact mechanism of antidepressant-induced galactorrhea is unknown. It has been suggested that elevated prolactin concentrations occur due to serotonin-mediated blockade of the tuberoinfundibular dopaminergic pathway or by direct serotonergic stimulation of the paraventricular hypothalamic nucleus (Demirci et al. 2015; Pathania et al. 2018). We calculated Naranjo adverse event scores of 5 (probable adverse event) for both medications (Naranjo et al. 1981) (Table 1). We do not have absolute certainty that there is not an alternative explanation as brain imaging and microscopy of the discharge were not performed. Nonetheless, clinicians should be aware that galactorrhea could occur with escitalopram or duloxetine in the absence of largely elevated prolactin concentrations.