LETTER TO EDITOR
Neuroleptic malignant syndrome after abrupt
discontinuation of neuroleptic and anticholinergic
drugs
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E xtrapyramidal and autonomic symptoms changed
degrees of consciousness, and aberrant laboratory
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results are the hallmarks of the relatively uncommon but
severe neuroleptic adverse response known as neuroleptic
malignant syndrome (NMS). The disease’s dysautonomia
symptoms and systemic consequences directly cause death.
Mortality is now estimated to be between 10 and 20 percent,
down from the early reports in the 1960s, which put it
at 76 percent.[1,2] NMS has a 0.02–3% prevalence among
patients treated with neuroleptic agents.[3] Withdrawal
NMS is an even rarer condition. The pathophysiology of
withdrawal‑related NMS symptoms may be connected to
cholinergic rebound, and withdrawal‑related NMS may be
a result of a dopaminergic system imbalance.
A 55‑year‑old female patient with schizophrenia was
taking risperidone 4 mg/day, trihexyphenidyl 2 mg/day,
and lorazepam 2 mg/d for the last 2 years, regularly. Her
medicine supply was over 3 days back and the patient missed
her follow‑up visit, resulting in the abrupt discontinuation
of her medications. The patient initially complained
of tremors in her limbs 2 days back, followed by fever,
stiffness in her limbs, and slowness in movement, which
developed over the next 2 days. The patient presented to
the emergency department with altered sensorium and
the above complaints. On examination, the patient was
in altered sensorium and disoriented to time, place, and
person, and mild pallor and icterus were present. On
Glasgow coma scale patient had score of 10/15 (Eye - 4,
Verbal - 4, Motor - 4), her blood pressure was 170/106 mm
of Hg; pulse was 109/ minute; and body temperature was
101°F; her systemic examination revealed lead pipe rigidity
of grade 4 on modified Ashworth scale and patient had
brisk (+3) deep tendon reflexes on Bilateral knee and elbow.
Laboratory investigation revealed hemoglobin of
9.9 gm/dl, serum sodium of 123.4 mmol/L, serum potassium
of 4.03 mmol/L, serum chloride of 89.9 mmol/L, Creatine
Phosphokinase - N Acetyl Cysteine of 2000 U/L, and 24‑hour
urine myoglobin of 87.07 ng/ml, and magnetic resonance
imaging (MRI) of the brain revealed no abnormality.
With a diagnosis of NMS, she was started with amantadine
200 mg/day, bromocriptine 5 mg/day, and an injection
of diazepam 30 mg/day along with supportive treatment
S277 © 2023 Industrial Psychiatry Journal | Published by Wolters Kluwer - Medknow
for electrolyte imbalance. Based on clinical response, the
decision was made to gradually increase bromocriptine to
7.5 mg/day, amantadine to 400 mg/day, and inj. diazepam to
40 mg/day over the next 2 days. The patient responded well
and all the laboratory investigations on day 6 of admission
came back normal, with rigidity of 1+ (on the modified
Ashworth scale). The score on the modified Simpson
Angus scale on day 6 was 22 (severe degree of movement
disorder), which decreased during treatment. Bromocriptine
and injection diazepam were gradually decreased to stop on
discharge, and amantadine was decreased to 200 mg/day
till discharge and gradually stopped during the next 4 weeks
on subsequent follow‑up visits, where we found the score
on the modified Simpson Angus scale had dropped to 4.
In our patient, the abrupt withdrawal of the anticholinergic
medication concomitantly with the neuroleptic medication
caused an impairment in the dopamine and acetylcholine
balance, where the cholinergic tone overrides the
dopaminergic tone. Previous case reports have postulated
that dopaminergic imbalance rather than dopaminergic
blockade might be the cause of NMS.[4] Most neuroleptic
drugs possess central and peripheral antimuscarinic
properties, so it is tempting to postulate that cholinergic
rebound causes withdrawal symptoms on discontinuation.[5]
Although the precise function of many drugs is still up for
discussion, our example suggests that a dopamine agonist
(such as bromocriptine, amantadine, levodopa, ropinirole,
and apomorphine) may help treat NMS.
Declaration of patient consent
The authors certify that they have obtained all appropriate
patient consent forms. In the form, the patient has given
her consent for her images and other clinical information
to be reported in the journal. The patient understands that
her name and initials will not be published and due efforts
will be made to conceal identity, but anonymity cannot be
guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
 Letter to Editor

Sameer Bhargava, Khushboo Bairwa, Yogesh Motwani 1990;81:168‑9.

5.
Department of Psychiatry, JNUIMSRC, Jaipur, Rajasthan, India
Address for correspondence:
Dr. Sameer Bhargava,
Department of Psychiatry, JNUIMSRC, Jaipur, Rajasthan, India.
E‑mail: Sameerbhargava25@gmail.com
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Gardos G, Cole JO, Tarsy D. Withdrawal syndromes
associated with antipsychotic drugs. Am J Psychiatry
1978;135:1321‑4.
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Received: 30 December 2022 the identical terms.

Revised: 31 July 2023
Accepted: 12 August 2023 Access this article online
Published: 30 November 2023
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REFERENCES Website: www.industrialpsychiatry.org
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How to cite this article: Bhargava S, Bairwa K, Motwani Y. Neuroleptic
Psychiatry 1985;142:1137‑45.
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4. Spivak B, Weizman A, Wolovick L Hermesh H, Tyano S,
anticholinergic drugs. Ind Psychiatry J 2023;32:S277-8.
Munitz H. Neuroleptic malignant syndrome during abrupt
© 2023 Industrial Psychiatry Journal | Published by Wolters Kluwer - Medknow
reduction of neuroleptic treatment. Acta Psychiatr Scand

Volume 32 | Supplement Issue 1 | November 2023 S278 Industrial Psychiatry Journal