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
Incident data |
Description |
|---|---|
| Year: 2025 Age group: adult Sex: female Active substances: Aripiprazole, haloperidol, levomepromazine Indication: Bipolar affective disorder (manic episode) ADR: Neuroleptic malignant syndrome Outcome: recovered |
During hospitalisation in a psychiatric ward due to a manic episode, the dose of aripiprazole was increased from 12.5 mg daily to 30 mg daily within a few days. Levomepromazine was continued and haloperidol was newly administered on two consecutive days. The patient developed a clinical deterioration characterised by muscular rigidity and reduced mobility. Vital signs showed tachycardia and elevated blood pressure with markedly increased creatine kinase (CK) levels. Subsequently, also fever and generalised rigidity of the limbs occurred. Because of the suspicion of neuroleptic malignant syndrome, the antipsychotic treatment was discontinued, and the patient was transferred to an intensive care unit. Treatment with lorazepam was initiated. The patient showed rapid clinical improvement with decreasing CK levels and resolution of muscular rigidity. She was transferred back to the psychiatric ward after two days without reintroduction of 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.
[5] Guinart D, Misawa F, Rubio JM, Pereira J, de Filippis R, Gastaldon C, et al. A systematic review and pooled, patient-level analysis of predictors of mortality in neuroleptic malignant syndrome. Acta Psychiatr Scand. 2021;144(4):329–41.
Reporting adverse drug reactions
Electronic reports via the ElVis portal
Note for marketing authorisation holders
If articles in this section refer to individual cases, these cases are already recorded in the Swiss spontaneous reporting system and have been transmitted to all responsible institutions. We ask affected marketing authorisation holders not to report these cases again (“back report”) to Swissmedic.