Neuroleptic malignant syndrome associated with antipsychotic treatment

Neuroleptic malignant syndrome (NMS) is a potentially life-threatening adverse drug reaction associated with antipsychotic treatment. It is characterised by high fever, muscular rigidity, autonomic instability (like irregular pulse or blood pressure) and altered mental status. Laboratory abnormalities such as elevated creatine kinase (CK) are commonly observed.

Neuroleptic malignant syndrome associated with antipsychotic treatment

Summary and recommendation

The pathophysiology of NMS is thought to involve a reduction in central dopaminergic activity, as well as dysregulation of the autonomic nervous system. Identified risk factors include male sex, dehydration, hypoxia, polypharmacy, pharmacokinetic interactions, rapid dose escalation, and renal impairment [1].

The incidence of NMS in patients of all age groups receiving antipsychotic treatment is estimated to range from 0.02% to 3% [2]. In general, all antipsychotics have the potential to induce NMS. First-generation antipsychotics are most frequently implicated and are associated with higher severity and incidence compared to second-generation agents. High-potency antipsychotics, such as haloperidol, are considered particularly high-risk, both as monotherapy and in combination with other medications [3].

Early recognition is crucial, as prompt discontinuation of the suspected medicinal product(s) and initiation of supportive therapy can lead to rapid clinical improvement. In contrast, unrecognised NMS may be fatal or result in permanent sequelae [4, 5].

Healthcare professionals should remain vigilant for the risk of NMS, particularly in the context of dose escalation or combination antipsychotic therapy. Patients receiving antipsychotic treatment should be closely monitored for early signs and symptoms of this condition.

Statutory duty of healthcare professionals to report adverse drug reactions (ADRs)

In Switzerland, healthcare professionals who are authorised to dispense or administer medicinal products are obligated to report severe and/or previously unknown side effects. Reports to Swissmedic can be entered and sent in the Electronic Vigilance Reporting Portal “ElViS”.

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References

[1] Tse L, Barr AM, Scarapicchia V, Vila-Rodriguez F. Neuroleptic malignant syndrome: a review from a clinically oriented perspective. Curr Neuropharmacol. 2015;13(3):395–406.

[2] Simon L, Hashmi MF, Callahan AL. Neuroleptic malignant syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024 [publication mise à jour le 19 avril 2024 ; citée en avril 2026]. Consultation : https://www.ncbi.nlm.nih.gov/books/NBK482282/

[3] Wijdicks EFM, Ropper AH. Neuroleptic Malignant Syndrome. N Engl J Med. 2024 Sep 26;391(12):1130-1138. doi: 10.1056/NEJMra2404606. PMID: 39321364.

[4] Oruch R, Pryme IF, Engelsen BA, Lund A. Neuroleptic malignant syndrome: an easily overlooked neurologic emergency. Neuropsychiatr Dis Treat. 2017 Jan 16;13:161-175. doi: 10.2147/NDT.S118438. PMID: 28144147; PMCID: PMC5248946.