Neuroleptic Malignant Syndrome (NMS) vs Serotonin Syndrome

In this article, we will take a close look at two serious neurological conditions: Serotonin Syndrome and Neuroleptic Malignant Syndrome. We will understand their causes, symptoms, and the crucial role of accurate diagnosis and treatment. The discussion will also touch on medical terms like hyperthermia, altered mental status, and autonomic instability.
Klara Hatinova

Klara Hatinova

Klara is postgraduate researcher in experimental psychology at the
University of Oxford.

A blue image with text saying "Serotonin Syndrome vs NMS"

What Is Serotonin Syndrome?

Serotonin syndrome is a potentially life-threatening condition that can occur due to an excess of serotonin, a chemical your neurons produce, in your brain. It's most often caused by excessive use of antidepressants or combining specific antidepressants, such as Zoloft and Prozac, Zoloft and Ashwagandha or Lexapro and Zoloft [1, 2, 3]. Notably, taking Lexapro and Wellbutrin together does not increase the risk of serotonin syndrome, which is why they are often prescribed together.

Symptoms of serotonin syndrome start suddenly or up to 24h after taking a high dose of serotonin-increasing medications. Common symptoms include: [3, 4, 5]

  • Altered mental status: including agitation, restlessness or confusion.
  • Increased neuromuscular activity: tremor or dyskinesia, dystonia or muscle rigidity or clonus (rapid and unexpected muscle contraction)
  • Autonomic Instability: fever or elevated body temperature, sweating, increased heart rate and blood pressure.

Serotonin syndrome is diagnosed using using the Hunter Serotonin Toxicity Criteria. A positive diagnosis requires the presence of more than one of the following:

  • clonus with agitation or diaphoresis or clonus in the eyes
  • tremor and hyperreflexia
  • hypertonia
  • temperature above 100.4 degrees F (38 degrees C), although this in itself is not sufficient to recognize serotonin syndrome, as elevated temperature is also a symptom of combining other drugs, such as Percocet with alcohol.
  • gastrointestinal side effects and nausea [6].

Therefore the presence of clonus is a prominent feature of serotonin syndrome.

Despite the potential severity of serotonin syndrome and the rising use of antidepressants, it is often overlooked. Up to 85% of physicians are unaware of this syndrome as a side effect of serotonergic drugs, which highlights the need to increase awareness to minimise the risks of serotonin syndrome, especially when prescribing and combining antidepressants [7].

What is NMS or Neuroleptic Malignant Syndrome?

Neuroleptic Malignant Syndrome (NMS) is a serious and potentially life-threatening condition resulting from using neuroleptic drugs, also known as antipsychotics [8]. These include clozapine and olanzapine, drugs commonly used in the treatment of psychiatric disorders such as schizophrenia or bipolar disorder [9, 10].

NMS is characterised by a combination of:

  • diffuse muscular rigidity, which can cause severe discomfort and limit mobility [11].
  • hyperthermia, or high body temperature, which can be dangerous if not properly managed [12].

These are symptoms similar to serotonin syndrome. Serotonin syndrome and NMS also share other symptoms, including:

  • altered mental status, in severe cases loss of consciousness [13]
  • irregular heart rate
  • autonomic symptoms, including autonomic dysfunction [14]

If you examine the blood profile of patients with NMS, you may also find increased levels of creatine kinase, a marker of muscle damage [12].

In contrast to serotonin syndrome, awareness of NMS is high in the medical community, especially since neuroleptic drugs are being used more sporadically.

The incidence of NMS is estimated between 0.2% and 3.2%, with the higher prevalence referring to in-patient samples in psychiatric hospitals. Furthermore, there are now new-generation antipsychotic drugs which significantly reduce the risks of NMS [11].

Klara Hatinova

Klara Hatinova

Klara is a postgraduate researcher in experimental psychology at the University of Oxford. She has worked across a spectrum of hot topics in neuroscience, including her current project measuring reinforcement learning strategies in Parkinson’s disease. Previously, she studied the efficacy of psilocybin as a therapy for critical mental health conditions and examined molecular circadian rhythms of migraine disorders. She completed her undergraduate degree in Neuroscience at the University of Glasgow and participated in a year abroad at the University of California, where she worked on a clinical trial for spinal cord injury.