Serotonin syndrome
Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs.[1] The symptoms can range from mild to severe, and are potentially fatal.[4][5][2] Symptoms in mild cases include high blood pressure and a fast heart rate; usually without a fever.[2] Symptoms in moderate cases include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea.[1][2] In severe cases, body temperature can increase to greater than 41.1 °C (106.0 °F).[2] Complications may include seizures and extensive muscle breakdown.[2]
Not to be confused with SSRI discontinuation syndrome.Serotonin syndrome
Serotonin toxicity, serotonin toxidrome, serotonin sickness, serotonin storm, serotonin poisoning, hyperserotonemia, serotonergic syndrome, serotonin shock
High body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, diarrhea[1][2]
Within a day[2]
Selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamine, methylene blue, pethidine (meperidine), tramadol, dextromethorphan, ondansetron, cocaine[2]
Based on symptoms and medication use[2]
Unknown[3]
Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs.[2] This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-hydroxytryptophan, St. John's wort, triptans, MDMA, metoclopramide, or cocaine.[2] It occurs in about 15% of SSRI overdoses.[3] It is a predictable consequence of excess serotonin on the central nervous system.[6] Onset of symptoms is typically within a day of the extra serotonin.[2]
Diagnosis is based on a person's symptoms and history of medication use.[2] Other conditions that can produce similar symptoms such as neuroleptic malignant syndrome, malignant hyperthermia, anticholinergic toxicity, heat stroke, and meningitis should be ruled out.[2] No laboratory tests can confirm the diagnosis.[2]
Initial treatment consists of discontinuing medications which may be contributing.[1] In those who are agitated, benzodiazepines may be used.[1] If this is not sufficient, a serotonin antagonist such as cyproheptadine may be used.[1] In those with a high body temperature, active cooling measures may be needed.[1] The number of cases of SS that occur each year is unclear.[3] With appropriate medical intervention the risk of death is low, likely less than 1%.[7] The high-profile case of Libby Zion, who is generally accepted to have died from SS, resulted in changes to graduate medical school education in New York State.[6][8]
Symptom onset is usually relatively rapid, SS encompasses a wide range of clinical findings. Mild symptoms may consist of increased heart rate, shivering, sweating, dilated pupils, myoclonus (intermittent jerking or twitching), as well as overresponsive reflexes.[6] (Many of these symptoms may be side effects of the drug or drug interaction causing excessive levels of serotonin rather than an effect of elevated serotonin itself.) Tremor is a common side effect of MDMA's action on dopamine, whereas hyperreflexia is symptomatic of exposure to serotonin agonists. Moderate intoxication includes additional abnormalities such as hyperactive bowel sounds, high blood pressure and hyperthermia; a temperature as high as 40 °C (104 °F). The overactive reflexes and clonus in moderate cases may be greater in the lower limbs than in the upper limbs. Mental changes include hypervigilance or insomnia and agitation.[6] Severe symptoms include severe increases in heart rate and blood pressure. Temperature may rise to above 41.1 °C (106.0 °F) in life-threatening cases. Other abnormalities include metabolic acidosis, rhabdomyolysis, seizures, kidney failure, and disseminated intravascular coagulation; these effects usually arising as a consequence of hyperthermia.[6][9]
The symptoms are often present as a clinical triad of abnormalities:[6][10]
Prognosis[edit]
Upon the discontinuation of serotonergic drugs, most cases of SS resolve within 24 hours,[6][9][70][71] although in some cases delirium may persist for a number of days.[29] Symptoms typically persist for a longer time frame in patients taking drugs which have a long elimination half-life, active metabolites, or a protracted duration of action.[6]
Cases have reported persisting chronic symptoms,[72] and antidepressant discontinuation may contribute to ongoing features.[73] Following appropriate medical management, SS is generally associated with a favorable prognosis.[74]
Epidemiology[edit]
Epidemiological studies of SS are difficult as many physicians are unaware of the diagnosis or they may miss the syndrome due to its variable manifestations.[6][75] In 1998 a survey conducted in England found that 85% of the general practitioners that had prescribed the antidepressant nefazodone were unaware of SS.[41] The incidence may be increasing as a larger number of pro-serotonergic drugs (drugs which increase serotonin levels) are now being used in clinical practice.[66] One postmarketing surveillance study identified an incidence of 0.4 cases per 1000 patient-months for patients who were taking nefazodone.[41] Additionally, around 14–16% of persons who overdose on SSRIs are thought to develop SS.[44]