Potential risk of psychiatric withdrawal events with domperidone for stimulation of lactation

Domperidone is a selective dopamine receptor antagonist approved locally for the treatment of delayed gastric emptying, gastro-oesophageal reflux, oesophagitis, and nausea and vomiting. The approved recommended dose for adults is 30 mg/day, which can be increased to a maximum of 40 mg/day. The maximum treatment duration generally ranges from one to four weeks depending on the indication but may be extended upon re-assessment of the patient’s need for continued treatment.

Domperidone has also been used off-label to promote lactation when deemed medically necessary by doctors. The prescribed dose and duration of treatment is based on the assessment of the individual patient’s situation. Domperidone-containing products have been registered in Singapore since 1989 and there are currently nine products registered.

Overseas reports of psychiatric withdrawal events with domperidone for stimulation of lactation

A small number of cases of psychiatric adverse events following sudden discontinuation or tapering of domperidone for stimulation of lactation have been reported overseas. These included nine cases identified by Health Canada and six cases by the US Food and Drug Administration (FDA).^1,2 These cases reported various adverse events such as agitation, anxiety, confusion, depression and insomnia. In most of these cases, the patients had been taking daily doses greater than 30mg and for longer than four weeks prior to the sudden discontinuation or tapering attempt.

It should be noted that the number of cases is small, and the onset of psychiatric symptoms could be independently associated with the cessation of breastfeeding or the emotional distress resulting from lactation difficulties, rather than being directly linked to domperidone discontinuation. These limit the assessment of a causal relationship between domperidone withdrawal and the reported psychiatric events. Nevertheless, there is a biological plausibility for the association. One postulated mechanism involves the abrupt decrease in plasma prolactin levels, which follows prolonged hyperprolactinaemia induced by long-term domperidone treatment.³ This could produce a sudden rise in dopaminergic activity and precipitate dopamine-mediated psychiatric events. Another hypothesis is that the higher doses of domperidone used for stimulation of lactation may result in significant penetration of the blood-brain-barrier, which is not generally associated with on-label doses.⁴

Local situation

As at 31 October 2024, HSA has not received any local adverse event report of psychiatric withdrawal events following domperidone use in stimulation of lactation from healthcare professionals. However, there was one medically unverified report from a consumer who reported that she experienced psychiatric events (including anxiety and depression) upon discontinuation of domperidone prescribed after delivery to help with breastfeeding. The dose and duration of domperidone prescribed was not provided and it was noted that she had a medical history of depression before pregnancy.

HSA’s advisory

Healthcare professionals may wish to consider the above information in their management of patients prescribed with domperidone for stimulation of lactation. They are also encouraged to report suspected serious adverse events related to domperidone to the Vigilance and Compliance Branch of HSA.

References     

1. https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SSR1691692252806

2. https://www.fda.gov/drugs/information-drug-class/information-about-domperidone

3. Can Pharm J (Ott) 2013;146:210-2. doi:10.1177/1715163513492928

4. Breastfeed Med 2022;17:1018-24