Dear Editor:

I read with great interest the recent article by Buttar et al1 detailing fatal consequences of the chronic neuroleptic malignant syndrome (NMS) from the United States. The authors prescribed the challenges of treating psychiatric patients with the possibility of NMS. They also indicated that ethnic groups concerning metabolic enzyme polymorphisms for antipsychotics, such as Asians and African Americans, seem to be at higher risk for NMS. I strongly agree with the article because I recently experienced a Japanese patient with schizophrenia who developed severe chronic NMS during telepsychiatry in the COVID-19 pandemic.

A 69-year-old Japanese male patient, under remote treatment by his attending psychiatrist for schizophrenia, was referred to our emergency room (ER) due to high fever of 39.5°C and muscle rigidity. The patient had been regularly treated by psychiatrists face to face for more than 20 years. However, the patient received medication through remote medicine (telepsychiatry) for 10 months because of the COVID-19 pandemic. At the time of referral, the patient was being treated with 9mg oral haloperidol once daily. On arrival, the patient was drowsy, temporal, and spatial disoriented, with no signs of compartment syndrome. In the ER, a series of examinations were performed, which suggested a diagnosis of multiple organ dysfunction syndrome (MODS).2 The laboratory results had shown creatine kinase (CK) levels > 30,000U/L (reference range 60–150U/L), leucocytosis 21,000/μmL, hemoconcentration (hemoglobin 16g/dL), renal dysfunction (serum creatinine, 2.1mg/dL; potassium, 5.8mmol/L), and liver dysfunction (serum alanine transaminase, 321U/L; γ-glutamyl transpeptidase, 88U/L). The computed tomography examination revealed no acute pathological modification. In the presence of severe rhabdomyolysis with subsequent MODS, the patient was admitted directly into the intensive care unit as a diagnosis of NMS. From the time of admission and over the following days, the patient received volume resuscitation and prophylactic antimicrobial regimen.

According to our hospital’s protocol, bacteriologic and viral screening were performed, and all the results were negative. After seven days of intensive care, the patient’s renal function progressively improved, as the serum CK values gradually decreased. But the patient’s muscle rigidity and the difficulty in swallowing lasted for another 10 days. After recovery, the patient said during telepsychiatry he was already finding it difficult to move due to muscle rigidity, which suggested the possibility of chronic course of NMS. Haloperidol was not readministered. Instead of antipsychotic medication, we considered alternative therapies, such as psychological interventions, behavioral interventions, and supportive environments, but due to the difficulty in utilizing effective resources under the COVID-19 pandemic, we adopted regular office visits.

The NMS is a rare and potentially fatal adverse drug reaction.3 Acute NMS is commonly known, but the chronic course of NMS is less known. Buttar et al listed high-risk patients for NMS, such as people treated with first generation antipsychotics and Asian and African population, that matched for the patient. Our case illustrates the difficulty of suspecting NMS symptoms in telepsychiatry. The COVID-19 pandemic triggered changes across healthcare systems, with many sectors seeing significant drops in patient visits. Although rapid transition to telepsychiatry allowed for the continued delivery of mental healthcare,4 valuable information from face-to-face examination is capable of being overlooked. Telepsychiatry can have unintended consequences, such as missing signs and symptoms that are obvious and easily recognizable in a face-to-face examination. However, these limitations do not diminish the value of telepsychiatry, which has become increasingly popular in recent years.5 Telepsychiatry can overcome these disadvantages by asking not only about psychiatric symptoms but also about physical symptoms. Moreover, our case supports the importance of checking of CK levels, that can only be obtained by patient visits. CK levels might need to be tested more routinely in some patients on antipsychotic medications who are at a high risk for NMS. However, the cost of making this a routine, standardized assessment is enormous and might not be cost-effective as a recommended monitoring test for all patients

The timing of this test could be at initiation, dosage increases, and at the appearance of general malaise or muscle rigidity. Therefore, it is important to first assess the patient’s general condition, including difficulty walking, lack of energy, falls, and decreased food intake. It has been suggested that COVID-19 infection might make patients more susceptible to developing NMS.6 Clinicians should be alert for the development of NMS during COVID-19 pandemic, as well as for behavioral changes seen in patients with COVID-19.


  1. Buttar K, Trigoboff E, Grace JJ. Neuroleptic malignant syndrome: Can be an unrecognized chronic fatal disease. Innov Clin Neurosci. 2020;17:10–12.
  2. Wang H, Ma S. The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome. Am J Emerg Med. 2008;26(6):711–715.
  3. Berman BD. Neuroleptic malignant syndrome: a review for neurohospitalists. Neurohospitalist. 2011;1(1):41–47.
  4. Sasangohar F, Bradshaw MR, Carlson MM, et al. Adapting an outpatient psychiatric clinic to telehealth during the COVID-19 pandemic: a practice perspective. J Med Internet Res. 2020;22(10):e22523.
  5. Looi JC, Allison S, Bastiampillai T, et al. Australian private practice metropolitan telepsychiatry during the COVID-19 pandemic: analysis of Quarter-2, 2020 usage of new MBS-telehealth item psychiatrist services. Australas Psychiatry. 2020 Dec 6:1039856220975294.
  6. Kajani R, Apramian A, Vega A, et al. Neuroleptic malignant syndrome in a COVID-19 patient. Brain Behav Immun. 2020;88:28–29.

With regards,

Takahiko Nagamine, MD, PhD

Department of Emergency Medicine and Psychiatric Internal Medicine at Sunlight Brain Research Center in Yamaguchi, Japan

Funding/financial disclosures. The authors have no conflict of interest relevant to the content of this letter. No funding was received for the preparation of this letter.