Neuroleptic Malignant Syndrome

Neuroleptic malignant syndromeNeuroleptic malignant syndrome (NMS) is a relatively rare, but life-threatening disorder associated with the use of psychotropic drugs, mainly neuroleptics, and antipsychotics. NMS is observed not only in psychiatric practice, but it can also occur in patients with any pathology and in healthy individuals in cases of prescribing antipsychotics.

Also, NMS can be observed when prescribing other dopamine-inhibiting drugs or when interrupting the use of dopamine agonists (in the latter case, according to some authors, we should not talk about the true malignant antipsychotic syndrome, but about NMS-like syndrome). In addition to antipsychotics, the neuroleptic malignant syndrome can occur as a result of taking drugs such as metoclopramide, desipramine, dothiepin, phenelzine, reserpine, amoxapine, cocaine, amphetamine.

The disorder was first described by J. Delay and co-authors in 1960 in patients receiving haloperidol, although similar observations have been observed before – since 1956, almost immediately after the introduction of antipsychotics into clinical practice.

Risk factors

Almost all antipsychotics, including atypical ones, can be the cause of MNS, but haloperidol, fluphenazine, and chlorpromazine are most often mentioned as the causes of MNS.

External risk factors, including those associated with antipsychotic therapy parameters, include:

  • high doses of antipsychotics, especially starting
  • rapid increase in antipsychotic load (doses of antipsychotic)
  • initial use of a high potency drug or transition to it 
  • prolonged use of drugs
  • intramuscular injection
  • joint use of predisposing drugs, such as lithium, anticholinergics, some antidepressants, clarithromycin 
  • withdrawal of antiparkinsonian drugs
  • past electroconvulsive therapy
  • inadequate control of neuroleptic extrapyramidal symptoms
  • high temperature and humidity

Factors associated with the physiological condition of patients include: 

  • dehydration of the body (the most important condition for the development of NMS)
  • physical exhaustion, including alimentary
  • alcoholism 
  • iron deficiency 
  • organic brain diseases with brain failure, such as mental retardation, post-traumatic encephalopathy, persistent extrapyramidal disorders, dementia (including the outcome of HIV infection), especially dementia with Levi bodies
  • organic lesions in the past – birth trauma, asphyxia, traumatic brain injury, infectious diseases of the central nervous system, toxemia of pregnancy in the mother, etc.
  • past NMS episodes, as well as the presence in the history of other side effects of antipsychotic therapy
  • a history of catatonia 
  • a history of allergic reactions
  • psychomotor agitation 
  • the postpartum period 
  • intercurrent infection
  • disturbances of water-electrolyte balance
  • thyroid dysfunction
  • hyperergic background with neurovegetative and allergic reactions 

Symptoms and signs of neuroleptic malignant syndrome

Symptoms of neuroleptic malignant syndrome usually include:

  • very high fever (102 to 104 degrees F)
  • irregular pulse
  • accelerated heartbeat (tachycardia)
  • increased rate of respiration (tachypnea)
  • muscle rigidity
  • altered mental status
  • autonomic nervous system dysfunction resulting in high or low blood pressure
  • profuse perspiration
  • excessive sweating.

Other symptoms may include liver or kidney failure, abnormally high potassium levels (hyperkalemia), major destruction of skeletal muscle tissue (rhabdomyolysis) or blood clots in veins and arteries.


The diagnosis of NMS is based on presence of signs and symptoms. At least five of the symptoms may testify that it is NMS.

Since the clinic of NMS is extremely polymorphic, the diagnosis of this disorder can be difficult even for experienced specialists. There are no generally accepted clear diagnostic criteria for malignant antipsychotic syndrome, various authors offer different diagnostic criteria. DSM-IV-TR provides the following diagnostic criteria :

  1. Muscle stiffness and fever developed during antipsychotic therapy.
  2. Sweating, dysphagia, tremor, impaired urination, altered consciousness, mutism, tachycardia, increased or lability of blood pressure, leukocytosis, increased serum CPK.

Symptoms of groups A and B should not be caused by other causes (C): neurological diseases, taking other drugs. As well as psychoses with catatonic symptoms (D). For the diagnosis of NMS, it is necessary to have both signs from group A and at least two signs from group B in the presence of conditions C and D. The diagnosis of NMS is a “diagnosis of exclusion”: it is made after exclusion of another pathology, which can lead to a similar clinical picture. To confirm this disease, in addition to a thorough clinical examination and a careful study of the anamnesis (including family history), the following additional studies are necessary.


Treatment of neuroleptic malignant syndrome comprises of withdrawal of neuroleptic medicines beneath a doctor’s supervision, quick measures to reestablish fitting water and supplement levels, and steps to lower the individual’s body temperature. Medicines endorsed as treatment may incorporate skeletal muscle relaxants, such as dantrolene; stimulators of dopamine generation and action, such as bromocriptine; and/or ceaseless perfusion of central apprehensive framework depressants, such as diazepam. Complications that will result from neuroleptic harmful disorder, such as kidney insufficiency, deficiency of oxygen reaching the tissues (hypoxia), and/or decreased alkalinity of the blood and tissues (acidosis) can be extremely serious and must be treated promptly. Once patients have recuperated from neuroleptic disorder, almost 87% will be able to endure an antipsychotic at some point in the future. 


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