Serotonin-Syndrome T88.7

Serotonin syndrome, also called serotonin toxicity, is a drug-induced potentially fatal complication, as a result of an adverse drug reaction, drug interaction, or overdose with one or more serotonergic pharmaceuticals, e.g., antidepressants, psychostimulants, and sometimes "ignored" serotonergic medication by recreational drugs (Mastroianni A et al. 2017).

Excessive synaptic stimulation of 5-HT2A receptors leads to autonomic and neuromuscular dysfunction with potentially life-threatening consequences. The clinical picture is caused by drugs that affect serotonin metabolism or act as serotonin receptor agonists. Monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and serotonin norepinephrine reuptake inhibitors are the drugs most commonly associated with serotonin syndrome. In most cases, these are 2 drugs that increase serotonin in different ways; the most common combination is a monoamine oxidase inhibitor with a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor.

Serotonin syndrome typically consists of a clinical triad of altered mental status, autonomic dysfunction, and neuromuscular agitation. Symptoms of serotonin syndrome include:

• Autonomic autonomic symptoms: e.g., pulse increase, sweating, nausea, diarrhea, rapid breathing, headache, pupillary dilation.
• Central nervous excitation symptoms: e.g. agitation, hallucinations, disturbances of consciousness, incoordination.
• Neuromuscular symptoms: e.g. convulsions, seizures, increased reflexes, tremor.

However, the syndrome is characterized by a great clinical heterogeneity, which may make the diagnosis difficult in practice. Symptoms can be mild and of short duration, but a prolonged course with life-threatening complications and lethal outcome are also possible.

The diagnosis can be made in patients with a history of exposure to a serotonergic drug who present with one or more of the following symptoms: spontaneous clonus, inducible clonus with agitation and diaphoresis, ocular clonus with agitation and diaphoresis, tremor and hyperreflexia, hypertension, temperature above 38 C with ocular or inducible clonus.

The diagnosis can be made in patients with a history of exposure to a serotonergic drug who present with one or more of the following symptoms: spontaneous clonus, inducible clonus with agitation and diaphoresis, ocular clonus with agitation and diaphoresis, tremor and hyperreflexia, hypertension, temperature above 38 C with ocular or inducible clonus.

Treatment is symptomatic and supportive. Therapy consists of immediate discontinuation of serotonergic agents, hydration, and supportive care to control blood pressure, hyperpyrexia, and respiratory and cardiac complications.

Sedation is best supported with benzodiazepines.

Refractory cases may respond to the antidote cyproheptadine, which must be administered orally or by gavage (the efficacy of cyproheptadine is unproven, but several case reports support its use in patients who do not respond to sedation and supportive care). (Wang RZ et al. 2016).

1. Bartlett D (2017) Drug-induced serotonin syndrome. Crit Care Nurse 37:49-54.
2. Mastroianni A et al. (2017) Serotonin syndrome due to co-administration of linezolid and methadone. Infez Med 25:263-266.
3. Tormoehlen LM et al (2018) Neuroleptic malignant syndrome and serotonin syndrome. Handb Clin Neurol 157:663-675.
4. Wang RZ et al. (2016) Serotonin syndrome: preventing, recognizing, and treating it. Cleve Clin J Med 83:810-817.