Selective Serotonin Reuptake Inhibitor Toxicity Medication

Updated: Apr 24, 2018
  • Author: Tracy A Cushing, MD, MPH, FACEP, FAWM; Chief Editor: Michael A Miller, MD  more...
  • Print

Medication Summary

Pharmacologic treatment of serotonin syndrome (SS) is largely based on anecdotal case reports and on animal models. Supportive care remains the basis of treatment; however, severe cases may benefit from the following interventions:

  • Adsorbent antidotes - Activated charcoal

  • Serotonin antagonists - Cyproheptadine

  • Sedatives and anticonvulsants - Lorazepam, diazepam, midazolam

  • Antihypertensives - Nitroprusside, esmolol

  • Paralytic neuromuscular blockade - Rocuronium, vecuronium


Antidotes, Other

Class Summary

These agents inhibit gastrointestinal absorption of certain toxic agents or irritants. Cyproheptadine, chlorpromazine, and risperidone have been reported to possibly be useful in serotonin syndrome (SS) through blockage of postsynaptic serotonin receptors. No formalized dosing regimens have been established; the following recommendations are based on case reports and reviews of serotonin toxicity treatment.

Activated charcoal (Actidose-Aqua, Actidose with Sorbitol, EZ-Char, Requa Activated Charcoal)

Activated charcoal is used as an emergency treatment for poisoning caused by drugs and chemicals, preventing absorption of a drug by adsorbing the drug in the intestine. The network of pores present in activated charcoal absorbs 100-1000 mg of drug per gram of charcoal. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption.

Theoretically, by constantly bathing the gastrointestinal tract with charcoal, the intestinal lumen serves as a dialysis membrane for reverse absorption of drug from intestinal villous capillary blood into the intestine. Activated charcoal does not dissolve in water.

For maximum effect, administer charcoal (1g/kg) within 30-60 minutes after poison ingestion. The addition of sorbitol results in hyperosmotic laxative action, which causes catharsis, further inhibiting intestinal absorption of toxic substances.


Cyproheptadine is a first-generation H1-receptor antagonist in blood vessels, the gastrointestinal tract, and the respiratory tract, with some anticholinergic and antiserotoninergic properties. It has been shown in animal studies and case reports to reduce symptoms of SS. [25] It may be helpful in mild-to=moderate cases of SS.

Chlorpromazine (Thorazine)

Chlorpromazine is a dopamine antagonist developed initially as a typical antipsychotic, but it also has some antiserotonergic properties. Case reports have described chlorpromazine improving the symptoms of SS. [26]

Following charcoal administration, chlorpromazine is a better choice in treating toxicity because it can be administered intravenously while cyproheptadine is not available in an intravenous form. However, it is best to avoid chlorpromazine if the drugs inducing serotonin toxicity have significant cardiogenic or epileptogenic properties.

Risperidone (Risperdal)

Risperidone is a 5-HT2a antagonist, used mainly as an atypical antipsychotic in the treatment of schizophrenia because of its antidopaminergic properties. In animal models, risperidone has been shown to completely inhibit the onset of symptoms of SS. Other potent 5-HT2a antagonists, such as ritanserin and pipamperone, have been shown to prevent the onset of SS when given in prophylactic doses. However, medications with specific 5-HT1a antagonism, such as propranolol, have not been shown to prevent SS, suggesting that perhaps the 5-HT2a receptor is the more important receptor implicated in the pathophysiology of SS. [27, 28]


Anxiolytics, Benzodiazepines

Class Summary

Benzodiazepines are considered a mainstay of serotonin syndrome (SS) treatment, particularly as a therapy for neuromuscular symptoms and seizures. They are also excellent for controlling agitated behavior.

Lorazepam (Ativan)

Lorazepam is a sedative with rapid onset and a relatively long half-life. By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, it may depress all levels of the central nervous system (CNS), including the limbic and reticular formation. Lorazepam's anticonvulsant effects last longer than those of diazepam or midazolam (4-6 h).

Diazepam (Valium, Diastat)

Diazepam modulates postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. It appears to act on part of the limbic system, thalamus, and hypothalamus to induce a calming effect. Diazepam has also been found to be an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders.

Diazepam rapidly distributes to other body fat stores. Twenty minutes after the drug's initial IV infusion, diazepam's serum concentration drops to 20% of maximum concentration. Individualize the dosage and increase it cautiously to avoid adverse effects.

Clonazepam (Klonopin)

Clonazepam is a benzodiazepine with anticonvulsant properties that may be useful in the setting of myoclonus.



Class Summary

Antihypertensives are used for the treatment of autonomic instability and malignant hypertension as evidenced by end-organ damage to the brain, heart, and/or kidneys.

Nitroprusside (Nitropress)

Nitroprusside produces arterial and venous vasodilation. It decreases afterload and preload and may produce a reflex tachycardia.

Esmolol (Brevibloc)

Esmolol is a cardioselective beta- 1-receptor blocker with a short duration of action that decreases both afterload and cardiac output in the setting of tachycardia/hypertension, and it is easily titratable.


Neuromuscular Blockers, Depolarizing

Class Summary

To control hyperreflexia, clonus, and hyperthermia, total neuromuscular paralysis may be required. Succinylcholine should be avoided in serotonin syndrome (SS), given the risk of hyperkalemia secondary to rhabdomyolysis.

Rocuronium (Zemuron)

Rocuronium is a nondepolarizing neuromuscular blocking agent with rapid to intermediate onset (depending on dose) and intermediate duration. It competes for cholinergic receptors at the motor end-plate to antagonize the action of acetylcholine, which in turn blocks neuromuscular transmission. Acetylcholinesterase inhibitors such as neostigmine and edrophonium antagonize action.


Vecuronium is a prototypic, nondepolarizing neuromuscular blocking agent that reliably results in muscular paralysis. For intubation and maintenance of paralysis, a continuous infusion may be used.

Infants are more sensitive to neuromuscular blockade activity and, although the same dose is used, recovery is prolonged by 50%. Vecuronium is not recommended for use in neonates.