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As wisely outlined by Rosie Sayers,(1) breastfeeding is best for the child and the mother. The recommendation by WHO to breastfeed in the first six months means that the off-label use of domperidone (to increase breast milk flow) by mothers will increase. La Leche League endorses this. In Australia, 5% of new mothers use domperidone. It is important, therefore, for family physicians to be aware of the domperidone withdrawal syndrome, and to advise that the withdrawal of domperidone be gradually tapered.
The failure to taper domperidone when stopping breastfeeding can sometimes be disastrous. In one example, a 41-year-old woman (patient wishes to remain anonymous, but has given information and consent for publication) delivered a baby by caesarian section at University College London Hospital, in February 2012. Six weeks after delivery her physician prescribed domperidone (10 mg TID) to increase her breast milk. Ten months later, in January 2013, she abruptly stopped domperidone and breastfeeding in order to conceive another child.
She immediately developed severe insomnia for 3 to 4 days at a time. She developed akathisia, severe anxiety, and difficulty swallowing. She was very depressed and felt she was 'putrefying inside', developing a delusion she had lost her internal organs. She suffered severe cognition and memory problems; she wandered for two hours in a supermarket unable to shop. Previously active as a lawyer with no earlier psychiatric history, she now lost all motivation and stopped taking care of herself. She planned suicide. On March 22, 2013, she was prescribed olanzapine 'for the psychosis', but only took an occasional dose. She was separately assessed by nine consultant psychiatrists, but no clear diagnosis was established. Ten months after stopping domperidone she was still having withdrawal side effects.
While domperidone readily blocks dopamine D2 receptors in the gastrointestinal system, it has been reported to be unable to permeate the blood-brain barrier.(2) However, there are reports of domperidone eliciting adverse motor side-effects,(3) indicating it can enter the brain. Domperidone is a potent antagonist of dopamine D2 receptors with an affinity for the D2 receptor twice that of haloperidol.(4) Therefore, if it enters the brain, the effects of long-term domperidone are expected to be similar to those of long-term haloperidol, including an increase in dopamine D2 or D2High receptors, associated with behavioural dopamine supersensitivity.(4)
The time course, the psychotic symptoms, and the basic pharmacology all indicate that the patient developed 'dopamine supersensitivity psychosis'(5) after stopping the long-term use of the domperidone antipsychotic.
Psychosis, insomnia, intense anxiety, and tachycardia caused by the sudden withdrawal of domperidone are not unusual.(6) Breastfeeding websites reveal disturbing stories of women who became extremely anxious, depressed, and psychotic upon sudden withdrawal of domperidone.
In this patient, the withdrawal reaction lasted ten months.
References
1. Sayers R. Breast is best: just maybe in private? Brit J Gen Pract 64(618) DOI: 10.3399/bjgp14X676573.
2. Laduron PM, Leysen JE. Domperidone, a specific in vitro dopamine antagonist, devoid of in vivo central dopaminergic activity. Biochem Pharmacol 1979; 28: 2161-2165.
3. Barone JA. Domperidone: a peripherally acting dopamine-2-receptor antagonist. Ann Pharmacother 1999; 33: 429-440.
4. Seeman P. All roads to schizophrenia lead to dopamine supersensitivity and elevated dopamine D2High receptors. CNS Neurosci Therap 2011; 17: 118- 132.
5. Chouinard G, Chouinard VA. Atypical antipsychotics: CATIE study, drug-induced movement disorder and resulting iatrogenic psychiatric-like symptoms, supersensitivity rebound psychosis and withdrawal discontinuation syndromes. Psychother Psychosom 2008; 77: 69-77.
6. Papastergiou J, Abdallah M, Tran A, Folkins C. Domperidone withdrawal in a breastfeeding woman. Can Pharm J (Ott) 2013; 146: 210-212.
Conflict of Interest:
None declared