Raloxifene for schizophrenia and symptoms of hyperprolactinaemia?

To the Editor

Hyperprolactinaemia, a common adverse effect of antipsychotic medication, is a condition of elevated serum prolactin with multiple health consequences including sexual dysfunction, galactorrhoea and amenorrhoea that can result in osteoporosis.

Hyperprolactinaemia was identified in Suzy, a 44-year-old woman with comorbid schizophrenia and pituitary microadenoma. The stable 3 mm adenoma, diagnosed 7 years previously, was treated with bromocriptine which appeared to induce her first psychotic episode. Key psychotic symptoms are frequent auditory and somatic hallucinations, delusional thinking and mild paranoia. Suzy also reported depression and memory difficulties. Previous antipsychotic treatment included olanzapine and clozapine, with unwanted side effects and perceived lack of symptom improvement. Suzy’s current treatment comprises zuclopenthixol decanoate injection 200 mg/fortnight, which has a propensity for prolactin elevation, and quetiapine 50 mg/day.

Suzy reported 4 years of amenorrhoea since commencing the zuclopenthixol depot. Prior to this, serum prolactin levels were stable at 1502 mU/L and her periods were largely regular. Current serum prolactin level was 2270 mU/L (adjusted reference range: 109–557 mU/L). Minimal galactorrhoea has been reported.

In line with emerging evidence of the psychoprotective effects of raloxifene (a selective oestrogen receptor modulator) for women with schizophrenia (Kulkarni et al., 2016), Suzy was trialled on 120 mg/day raloxifene for 12 weeks. She reported menstruating after 8 weeks of treatment with a progesterone level of 23 nmol/L, suggesting that ovulation had occurred. Menstruation occurred in the context of ongoing zuclopenthixol use and only a slight drop in prolactin level to 2217 mU/L (2202 mU/L after 12 weeks of raloxifene). Amenorrhoea resumed with cessation of raloxifene.

Twelve weeks of raloxifene treatment improved Suzy’s psychotic symptoms (7-point change, Positive and Negative Syndrome Scale), mood (6-point change, Montgomery–Åsberg Depression Rating Scale) and cognitive functioning (8-point total scale change, Repeatable Battery for the Assessment of Neuropsychological Status).

This is the first case to report resumption of menses with raloxifene in a woman with hyperprolactinaemia resulting from pituitary microadenoma plus antipsychotic use. While little is known about the effects of raloxifene in premenopausal women, it does appear to cause ovarian stimulation (Premkumar et al., 2007). Raloxifene has been shown to decrease prolactin levels in postmenopausal women (Cheng et al., 2004); however, this did not appear to be the case in our premenopausal patient. As patients taking prolactin-elevating antipsychotics are at high risk of bone mineral density depletion from hyperprolactinaemia-induced hypogonadism, raloxifene (currently indicated for the prevention and treatment of postmenopausal osteoporosis) may promote bone strength while reducing psychotic illness severity. Additional work is required to determine the effects of raloxifene in this patient group.