Treatment of Neuroleptic Malignant Syndrome with Electroconvulsive Therapy in an Adolescent with Psychosis

To the Editor:

Neuroleptic malignant syndrome (NMS) is a life-threatening neurologic complication associated with the use of neuroleptic agents, and is characterized by fever, rigidity, autonomic nervous system dysfunction, mental status change, mutism, leukocytosis, and elevated creatine kinase. NMS can occur after the use of any atypical antipsychotic including clozapine (Erol et al. 2013).

Many patients with NMS improve spontaneously with the cessation of the neuroleptic, or respond to treatment with a dopamine agonist and a muscle relaxant. A proportion of patients show an incomplete response and should receive a course of electroconvulsive therapy (ECT). The case reports suggest that ECT is effective in the treatment of NMS (Hermesh et al. 1987), and the response to ECT appears to be faster than that to drugs, although no direct comparison exists (Trollor and Sachdev 1999). In a recent review, Luchini et al. stated that ECT should be considered as first-line treatment in patients with malignant catatonia and NMS, and, in general, in all catatonic patients who are refractory or partially responsive to benzodiazepines, and early intervention with ECT is encouraged to avoid undue deterioration of the patient's medical condition (Luchini et al. 2015). ECT may be a suitable alternative to neuroleptics in patients who are psychotic and have developed NMS. In addition, ECT may be a good choice because it may be difficult to differentiate NMS from lethal catatonia, and the life-saving role of ECT in the treatment of lethal catatonia is well described (Trollor and Sachdev 1999). However, there are unrealistic fears regarding ECT in adolescents.

Here, we report on an adolescent referred for psychotic symptoms who developed NMS after treatment with olanzapine, haloperidol, and quetiapine, who was then treated successfully with ECT.

Case Report

AB was a 17-year-old girl who was referred to an adult psychiatry clinic by her family because of her paranoid delusions. Her family said that for the last month, the girl had been afraid of going to school, claiming that someone was following her and that everyone in the school was malicious. She did not want to eat her meals because she thought they were poisoned. She insisted that someone had made changes to the identity cards of all family members. She was hospitalized with a diagnosis of acute psychosis in a psychiatry unit and olanzapine i.m. 20 mg/day was started. After 6 days, because of her hostile behavior, 15 mg/day i.m. haloperidol and 7.5 mg/day lorazepam were added to olanzapine. Three weeks later, the patient was transferred to our child and adolescent inpatient unit because of treatment resistance. On the 1st day at our clinic, she had a flat affect, marked rigidity with lead-pipe appearance, and marked parkinsonian symptoms. Altough haloperidol was stopped and biperiden was added, there was minimal change in her extrapyramidal sypmtoms. It was decided to replace olanzapine with quetiapine and olanzapine was stopped gradually. Quetiapine 300 mg/day was started and increased to 600 mg/day in six days. The patient's rigidity continued, and there was an increase in both her psychotic symptoms and her anxiety. She became apathic and confused, and her movements were slower. Both urinary and fecal incontinance emerged. Her body temperature, blood pressure, and per minute heart beat became unstable, with a slight increase. Her body temperature fluctuated between 36 and 37.9°C throughout the day. Laboratory findings revealed leukocytosis (13100/mm³) and serum creatine kinase (CK) elevation (1547 U/L). NMS was suspected; therefore, antipsychotic treatment was stopped and a neurology consultation was made. ECT was prescribed on an emergency basis because of the patient's deteriorating physical and mental health. Her mental state and autonomic symptoms improved considerably after the fifth bilateral ECT. After 12 sessions of bilateral ECT, her psychotic symptoms dissappeared and her medical condition was satisfactory. Her rigidity decreased markedly. No complications of ECT were observed.

Discussion

NMS has been reported to be primarily associated with antipsychotics and polypharmacy (Su et al. 2014). In this case, it is not clear which agent – olanzapine, haloperidol, quetiapine, or all of them together – caused NMS; however, using initially high doses of the i.m. forms of multiple antipsychotics seems to be a risk factor.

ECT was planned initially for treatment of both NMS and the increased psychotic symptoms. Ghaziuddin et al. reported the safe use of ECT in a very similar case with delayed diagnosis of NMS (Ghaziuddin et al. 2002). In a review including 55 adult and adolescent NMS cases treated by ECT, ECT was reported to be relatively safe and effective in many individuals with NMS, even when drug therapy had failed (Trollor and Sachdev 1999). The autonomic dysfunction in NMS increases the likelihood of cardiovascular problems with ECT. However, the patient presented here tolerated ECT well, with no adverse effects, and her autonomic dysfunction disappeared after a few ECT sessions.

In conclusion, ECT seems to be an effective and relatively safe alternative treatment when antipsychotics result in NMS in adolescents.