Serotonin Syndrome Versus NMS (Neuroleptic Malignant Syndrome)

Serotonin Syndrome Versus NMS Similarities

Over the past few decades, attention has been drawn to two uncommon but potentially fatal adverse responses to psychiatric drugs: serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS). These two drug-induced illnesses have certain clinical traits or presentations in common. Due to variations in their administration and therapy, it is imperative to distinguish between these significant illnesses. It’s crucial to spread knowledge of the similarities and differences in how they show themselves.

Although it can sometimes happen after starting a single serotonergic medication, SS typically develops from concurrently using several serotonergic medicines. Serotonin syndrome may also be triggered by drug interactions that cause the central nervous system (CNS) to produce too much serotonin.

There is a range of theories on how SS functions. Serotonin levels may increase due to medications that cause a rise in release, decreased uptake or metabolism of serotonin, or excess serotonin precursors or agonists. Several medications and drug classes have been linked to occurrences of SS, including TCAs, SSRIs, SNRIs, MAOIs, triptans, nefazodone, buspirone, mirtazapine, carbamazepine, tramadol, linezolid, MDMA (ecstasy), dextromethorphan, St. John’s wort, lithium, methadone, cocaine, levodopa, reserpine, and amphetamines. The frequency of SS resulting from using these agents is mainly unknown.

The use of neuroleptic agents precipitates NMS. The incidence of NMS varies with a range of 0.02–2.4% in patients being treated with neuroleptics. These agents include dopamine antagonists such as antipsychotics and antiemetics. Also, abrupt withdrawal of dopamine agonists, for instance, those used in managing Parkinson’s disease, may produce signs and symptoms correlating with NMS. Interestingly, NMS does not necessarily correspond with high doses of antipsychotics, as it can also occur with lower doses.

Neuroleptic Malignant Syndrome Vs Serotonin Syndrome Risk Factors

The solitary risk factor identified in SS is the concurrent use of serotonergic agents. A list of agents associated with SS can be found in the table below within the article. The individual risk with each serotonergic medication listed in the table is mainly unknown.

However, avoiding the concomitant use of multiple serotonin-enhancing medications can help minimize the risk of developing SS. Talarico et al presented two cases of SS due to drug interactions involving citalopram with two CYP 2D6 inhibitors, cimetidine, and topiramate. Each patient’s symptoms resolved within a week of discontinuing the offending agents.

Another risk for SS may be with illicit drugs, mainly when used in patients concurrently taking a serotonin-enhancing drug. One case, reported by Joksovic, showed that “bath salts,” a synthetic derivative of cathinone, induced a state of serotonin toxicity. Cathinone is a naturally occurring psychostimulant. These synthetic cathinones are believed to enhance the release of monoamines and block their reuptake, resulting in symptoms consistent with SS.

Additionally, the use of cocaine in patients taking antidepressants, specifically SSRIs, was found to be one of the most common causes of serotonin toxicity. MDMA used concomitantly with other drugs has been connected with many fatalities. MDMA exerts its effects by increasing neurotransmitters in the CNS, serotonin, norepinephrine, and dopamine. Combining MDMA with other serotonin-modifying agents increases the risk of fatalities due to serotonin toxicity.

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26,733

There were 26,733 exposures to SSRIs reported in 2004, of which 7.5 percent involved serotonin syndrome.

Source: Toxic Exposure Surveillance System

5 and 11.6%

The mortality rate of NMS is between 5 and 11.6 percent, while the mortality rate of SS is less than 1 percent.

Source: Birmes P, Coppin D, Schmitt L, Lauque D. Serotonin syndrome: a brief review. 

Main Differences Between Serotonin Syndrome Vs NMS

Neuroleptic malignant syndrome (NMS) and serotonin syndrome (SS) are both rare but potentially life-threatening conditions that can occur due to the use or withdrawal of certain medications that affect the brain. However, they have different causes, clinical features, and time courses.

NMS is usually triggered by using dopamine antagonists, such as antipsychotics or antiemetics, or the abrupt withdrawal of dopamine agonists, such as those used for Parkinson’s disease. NMS reduces dopamine activity in the brain, leading to muscle rigidity, fever, altered mental status, and autonomic instability.

NMS typically develops over days to weeks after exposure to the causative agent. SS is usually caused by using serotonin agonists, such as antidepressants, triptans, or recreational drugs, or excess serotonin precursors, such as tryptophan or St. John’s wort.

SS increases serotonin activity in the brain, leading to neuromuscular hyperreactivity, such as tremors, hyperreflexia, myoclonus, fever, altered mental status, and autonomic instability. SS typically develops over 24 hours after exposure to the causative agent. Both conditions require prompt recognition and treatment to prevent severe complications and death.

Neuroleptic Malignant Syndrome Vs Serotonin Syndrome Vs Malignant Hyperthermia

Neuroleptic malignant syndrome (NMS), serotonin syndrome (SS), and malignant hyperthermia (MH) are all rare but potentially life-threatening conditions that can cause hyperthermia and muscle rigidity, among other symptoms. However, they have different causes, clinical features, and treatments that require differentiation.

NMS is usually triggered by the use or withdrawal of medications that affect dopamine activity in the brain, such as antipsychotics or antiemetics. NMS reduces dopamine activity in the brain, leading to muscle rigidity, fever, altered mental status, and autonomic instability. NMS typically develops over days to weeks after exposure to the causative agent. SS is usually caused by the use or withdrawal of medications that affect serotonin activity in the brain, such as antidepressants, triptans, or recreational drugs.