Serotonin syndrome

Serotonin syndrome is a potentially life-threatening drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs. The excess serotonin activity produces a spectrum of specific symptoms including cognitive, autonomic, and somatic effects. The symptoms may range from barely perceptible to fatal. Numerous drugs and drug combinations have been reported to produce serotonin syndrome.

Signs and symptoms

Symptom onset is usually rapid, often occurring within minutes, and include the following:

• Cognitive: headache, agitation, hypomania, confusions, hallucinations, coma
• ANS: shivering, sweating, hyperthermia, hypertension, tachycardia, nausea, diarrhea
• SNS: twitching, tremors

Pathophysiology

Serotonin is a neurotransmitter involved in multiple states including aggression, pain, sleep, appetite, anxiety, depression, migraine, and vomiting. In humans the effects of excess serotonin were first noted in 1960 in patients receiving a MAOI and tryptophan. The syndrome is caused by increased serotonin in the central nervous system. Other neurotransmitters may also play a role; NMDA receptor antagonists and GABA have been suggested as affecting the development of the syndrome.

Causes

A large number of medications either alone in high dose or in combination can produce serotonin syndrome.

Class	Drugs
Antidepressants	MAOIs, TCAs, SSRIs, SNRIs, bupropion, nefazodone, trazodone, mirtazapine
Opioids	tramadol, pethidine, fentanyl, pentazocine, buprenorphine, oxycodone, hydrocodone
CNS stimulants	MDMA, MDA, phentermine, diethylpropion, amphetamine, sibutramine, methylphenidate, methamphetamine, cocaine, dextromethorphan
5-HT1 agonists	triptans
Psychedelics	5-Methoxy-diisopropyltryptamine, LSD
Herbs	St John's Wort, Syrian rue, Panax ginseng, Nutmeg, Yohimbe
Others	tryptophan, L-Dopa, valproate, buspirone, lithium, linezolid, 5-hydroxytryptophan, chlorpheniramine, risperidone, olanzapine, ondansetron, granisetron, metoclopramide, ritonavir

Diagnosis and treatment

Diagnosis of serotonin syndrome includes observing the symptoms produced and a thorough investigation of the patient's history. The syndrome has a characteristic picture but can be mistaken for other illnesses in some people, particularly those with neuroleptic malignant syndrome. No laboratory tests can currently confirm the diagnosis. Treatment consists of discontinuing medications which may contribute and in moderate to severe cases administering a serotonin antagonist. An important side-treatment includes controlling agitation with benzodiazepine sedation.

See Also

• Serotonin