Catatonia Induced by D2 Receptor Antagonist Antiemetics in a Patient With Multiple Sclerosis

Catatonia is believed to result from disruption of the cortico-striato-thalamo-cortical circuits, involving an imbalance in dopaminergic neurotransmission.¹ Given this, dopamine blockade via D2 receptor (D2R) antagonist antipsychotics has been implicated in precipitation of this syndrome.² Similarly, metoclopramide—a D2R antagonist antiemetic—has been associated with neuroleptic malignant syndrome,^3,4 considered a type of malignant catatonia by some experts,¹ and catalepsy, a sign of catatonia, in animal models.⁵ Here, we describe a rare case of catatonia correlated with abuse of D2R antagonist antiemetic medications.

Case Report

We present the case of a 52-year-old man with relapsing-remitting multiple sclerosis (MS) and hypertension treated with fingolimod 0.5 mg/day and telmisartan 80 mg/day. He was also being treated for insomnia with quetiapine 300 mg/day, cyamemazine 100 mg/day, mirtazapine 15 mg/day, pregabalin 50 mg/day, and lorazepam 1 mg/day, with no other relevant psychiatric or medical history.

The patient developed nausea with no other clinical symptoms and began taking metoclopramide and domperidone erratically, exceeding recommended doses for approximately 2 weeks. Subsequently, he exhibited behavioral changes described by his family as repetitive purposeless movements, mutism, fixed gaze, and reduced cooperation. Two days after symptom onset, he was brought to the emergency department presenting nonpurposeful excessive motion with frequent stereotypies interspersed with periods of sitting abnormally still (for less than 1 minute), while verbally unresponsive to most questions and showing minimal interaction with stimuli, decreased blinking, occasional echolalia, ambitendency, and perseveration of movements (16 points on the Bush-Francis Catatonia Rating Scale⁶). There was no autonomic abnormality, fever, or rigidity.

Initial examination was conducted by the internal medicine and neurology departments. Blood and urine analyses were unremarkable. Brain magnetic resonance imaging showed no new lesions beyond those previously documented: significant supratentorial and infratentorial lesion load and no gadolinium-enhancing or diffusion-restricted lesions. Lumbar puncture showed normal cytochemical and microbiological cerebrospinal fluid parameters, with negative antineuronal antibodies.

A lorazepam challenge test of 2.5 mg orally was performed, yielding a positive response. The patient was subsequently prescribed lorazepam 1 mg every 6 hours, leading to complete symptom resolution within 12 hours. Upon discharge, he was advised to discontinue antiemetics and continue lorazepam 1 mg twice daily. Six months later, he remained asymptomatic with no recurrence of catatonia.

Discussion

This is the first published case, to our knowledge, linking catatonia to D2R antagonist antiemetic medications. Psychiatric causes were excluded, as the patient exhibited no new or worsening psychopathology, and other medical causes, including MS relapse, were ruled out by the absence of new laboratory or imaging abnormalities. Additionally, he had not started any new medication other than metoclopramide and domperidone.

Metoclopramide is known to cause several central nervous system adverse effects, including extrapyramidal symptoms, through its ability to cross the blood-brain barrier (BBB) and block central dopaminergic pathways. These properties have been associated with neuroleptic malignant syndrome and catalepsy.^3–5 We propose that excessive use led to central dopaminergic imbalance, thereby precipitating catatonia.^1,2 The drug’s central effects were likely exacerbated by increased BBB permeability due to MS, which occurs even in the absence of enhancing lesions.^7,8

We also propose domperidone as a contributing agent. Despite being primarily a peripheral dopamine D2R antagonist with minimal central nervous system penetration and rare associated adverse effects, BBB compromise, as in this case, may have permitted greater central exposure and subsequent adverse effects, as documented elsewhere.⁹

Although the patient had been taking quetiapine 300 mg/day with no previously reported adverse effects, its contribution to the episode should also be considered. Like other D2R antagonist antipsychotics, quetiapine has been associated with catatonia, with 2 case reports suggesting a probable causal relationship.^10,11 These occurrences are rare compared with high-potency first-generation antipsychotics, possibly reflecting quetiapine’s relatively low D2R affinity. However, cumulative dopaminergic blockade resulting from the combination of quetiapine and excessive antiemetic doses may have increased susceptibility to the development of the present episode.

This case highlights the potential for metoclopramide and domperidone—D2R antagonist antiemetics—to induce catatonia, at least as contributing agents, warranting careful consideration and monitoring of their use in patients with neurological vulnerabilities or receiving concomitant antipsychotic treatment. Clinicians should remain vigilant for behavioral or motor changes, particularly when BBB integrity might be compromised, such as in MS. Prompt recognition and treatment can result in rapid symptom resolution and prevent serious complications.

Article Information

Published Online: June 4, 2026. https://doi.org/10.4088/PCC.25cr04173
© 2026 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2026;28(3):25cr04173
Submitted: December 21, 2025; accepted February 23, 2026.
To Cite: Silva FS, Lemos MG, Baronet P. Catatonia induced by D2 receptor antagonist antiemetics in a patient with multiple sclerosis. Prim Care Companion CNS Disord 2026;28(3):25cr04173.
Author Affiliations: Department of Psychiatry, Unidade Local de Saúde de Santa Maria, Lisbon, Portugal (all authors).
Corresponding Author: Francisco S. Silva, MD, Serviço de Psiquiatria e Saúde Mental, Piso 4 | Unidade Local de Saúde Santa Maria – Avenida Professor Egas Moniz, 1649-035 Lisbon, Portugal ([email protected]).
Financial Disclosure: None.
Funding/Support: None.
Patient Consent: Consent was received from the patient to publish the case report, and information has been de-identified to protect patient anonymity.
ORCID: Francisco S. Silva: https://orcid.org/0000-0001-7943-4562; Magda G. Lemos: https://orcid.org/0000-0002-5284-9909