Understanding Serotonin Syndrome and Neuroleptic Malignant Syndrome
Key Takeaway
Serotonin syndrome is typically caused by an excess of serotonin, while Neuroleptic Malignant Syndrome is often a reaction to antipsychotic drugs, although the symptoms can overlap.
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].
Serotonin Syndrome and Neuroleptic Malignant Syndrome
Now that we understand what serotonin syndrome and NMS are, it is important to discuss their similarities and differences, as well as whether it is possible to have both serotonin syndrome and NMS.
Both serotonin syndrome and NMS are conditions on the same spectrum of syndromes relating to motion and mental state. As such, their comparison is well-defined in the literature.
However, serotonin syndrome is a result of drug toxicity (the dose being too high), whereas NMS is a sign of idiosyncratic drug reaction, that is, a drug reaction that occurs rarely and cannot be reliably predicted [15].
Serotonin syndrome and Neuroleptic Malignant Syndrome (NMS) are two potentially life-threatening conditions that can occur due to the use of certain medications, particularly psychotropic drugs. They share many clinical features, making them difficult to distinguish, but they are caused by distinct pathologies [15, 8, 16].
SS is typically associated with an excess of serotonin in the body, often due to the use of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs). Patients with serotonin syndrome have lower fevers but more gastrointestinal side effects and muscle spasms. In contrast, NMS patients present with higher fevers and muscle rigidity [15, 8, 16].
Patients with serotonin syndrome have lower fevers but more gastrointestinal side effects and muscle spasms.
Can I Get Serotonin Syndrome and NMS?
In some cases, patients may present with symptoms of both serotonin syndrome and NMS, particularly if they are taking a combination of serotonergic and dopaminergic medications [10]. This can be exacerbated by specific SSRIs, such as fluoxetine, which has a longer half-life than Lexapro. The overlap in the symptomatology between serotonin syndrome and NMS also makes accurate diagnosis difficult [17, 10].
Treatment of Serotonin Syndrome and NMS
Treatment for both serotonin syndrome and NMS primarily involves discontinuing the serotonergic drug or dopamine antagonist, respectively, combined with specialist care and detoxification procedures. These may include professionally administered electrolytes, intubation or sedation to relieve kinetic side effects. Additional medication may be administered if these do not relieve the symptoms. However, it's important to accurately diagnose the condition, as using incorrect medications could enhance drug interactions and exacerbate the symptoms [16].
