Selective Serotonin Reuptake Inhibitor Toxicity 

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

Overview

Background

Selective serotonin reuptake inhibitors (SSRIs), widely prescribed medications for the treatment of depression, obsessive-compulsive disorder, bulimia, anorexia nervosa, panic disorder, anxiety, and social phobia, have a high therapeutic to toxicity ratio. However, although they are associated with less toxicity than tricyclic antidepressants (TCAs), they are often involved in co-ingestions that can precipitate the potentially lethal serotonin syndrome (SS). (See Etiology.) 

SS represents a constellation of signs and symptoms that manifest in the neuromuscular, autonomic nervous, and gastrointestinal systems, in which concentrations of serotonin receptors are highest. SS represents the most severe end of a spectrum of serotonin excess and is characterized by mental status changes, neuromuscular hyperactivity, and autonomic instability. (See Prognosis and Presentation.)[1, 2]

The majority of antidepressants prescribed in the United States are from the SSRI family.[3, 4] Commonly prescribed SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), and fluvoxamine (Luvox). SSRI toxicity and other adverse drug reactions can occur with overdose, in combination with other medications, or, infrequently, at therapeutic doses. (See Etiology.)

SS is often caused by combinations of SSRIs with other proserotonergic agents, including:

  • Monoamine oxidase inhibitors (MAOIs)

  • TCAs

  • Trazodone (Desyrel)

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)

  • Norepinephrine-dopamine reuptake inhibitors

  • Lithium

  • Opioids

  • Amphetamine/stimulants - Including methylphenidate (Ritalin); 3,4 methylenedioxymethamphetamine (MDMA, Ecstasy); cocaine; and herbal dietary supplements or nutraceuticals (St. John's wort, ginseng, and S-adenosyl-methionine)

All of these affect the production, release, or breakdown of serotonin at the presynaptic cleft, thereby increasing its levels and toxicity. Less frequently, SS can be precipitated by an overdose of a single SSRI.

Venlafaxine (Effexor) and duloxetine (Cymbalta) are serotonin-norepinephrine reuptake inhibitors (SNRIs) that are also associated with serotonin toxicity, as is the tetracyclic drug mirtazapine (Remeron), an alpha-2 adrenergic heteroreceptor blocking agent that causes increased norepinephrine and serotonin release in addition to blocking serotonin receptors.

Trazodone is a tetracyclic drug that blocks serotonin reuptake and also has an antagonistic effect at the serotonin 5HT2 receptor site.

Bupropion (Wellbutrin), a norepinephrine-dopamine reuptake inhibitor classified as neither an SSRI nor a TCA, is another commonly prescribed antidepressant that can precipitate SS; it is commonly involved in fatal antidepressant overdoses.

Several opioids are serotonergic and have been associated with SS. These include meperidine (Demerol), tramadol (Ultram), dextromethorphan, and pentazocine.

Numerous reports have described SS precipitated by combination of serotonergic drugs with the antimicrobial agent linezolid, which exhibits monoamine oxidase (MAO)-type effects.[5]

Pharmacokinetics

SSRIs are metabolized in the liver by cytochrome P-450 mixed function oxidase (MFO) microsomal enzymes. They are highly bound to plasma proteins and have a large volume of distribution. Peak plasma levels are reached in 2 to 10 hours. Half-lives for SSRIs are variable, but most have a half-life of 20 to 24 hours.[6] A notable exception is fluoxetine (Prozac) and its active metabolite, norfluoxetine, which have half-lives of 2 to 4 days and 8 to 9 days, respectively.

Hence, addition of serotonergic medications to a patient's regimen must not occur until 2 to 3 weeks after discontinuation of an SSRI. Some recommend a 5-week "wash-out" period for fluoxetine prior to initiation of an MAOI. (See Treatment.)[7, 8]

Complications

Complications of SSRI toxicity can include the following:

  • Seizures

  • Arrhythmia

  • Rhabdomyolysis

  • Disseminated intravascular coagulation

  • Acute renal failure

  • Respiratory failure

Etiology

Serotonin, or 5-hydroxytryptamine (5HT), is a neurotransmitter found in the central and peripheral nervous system. Serotonin is produced in the brainstem’s raphe nuclei from L-tryptophan and is then stored in presynaptic vesicles. Neuronal activation causes release of 5HT into the synapse. Excess serotonin is taken back up into presynaptic vesicles by an active transport mechanism or it is locally metabolized by monoamine oxidase (MAO) to 5-hydroxyindoleacetic acid. Systemic metabolism is through MFOs of the liver.

Inhibition of particular MFOs by other medications or plant materials (eg, grapefruit) may cause increased drug effect from decreased metabolism.[6]

SS is most often caused by simultaneous ingestion of 2 or more proserotonergic medications, which may be associated with therapeutic error, idiopathic response, or intentional overdose.[9, 10]

A recently increased dose of a chronic medication or a new addition to an extensive medication regimen is an important component of the history that may provide the diagnosis. Use of over-the-counter medications or dietary supplements in addition to prescribed serotonergic medications is also an important etiology.

Seven distinct 5HT receptors, which can be further divided into specific subtypes, exist and produce a wide variety of physiologic effects. This diverse activity gives rise to the multiple signs and symptoms of serotonin toxicity.[11, 12]

Mechanisms of serotonin increase

Excess serotonergic activity can be precipitated through any of the following mechanisms[13] :

  • Direct 5HT-receptor stimulation - Buspirone (BuSpar), triptans (Imitrex, Amerge, Zomig, others), lithium, carbamazepine (Tegretol), lysergic acid diethylamide (LSD), mescaline-containing cacti (peyote and others)

  • Direct 5HT release from stored vesicles - Amphetamines, MDMA, cocaine, reserpine, levodopa, MAOIs, codeine, dextromethorphan, pentazocine

  • Increased availability of 5HT precursors - L-tryptophan

  • Decreased 5HT reuptake - SSRIs, trazodone (Desyrel), nefazodone, venlafaxine (Effexor), TCAs, dextromethorphan, tramadol (Ultram), meperidine (Demerol), cocaine, Hypericum species (St. John's wort), amphetamines, carbamazepine (Tegretol), methadone, linezolid

  • Decreased 5HT degradation - MAOIs, St. John's wort

Receptor locations and symptoms

Large dosages or combinations of any of the drugs in the above lists can produce serotonin toxicity or SS. The physiologic manifestations of SS are largely due to stimulation of 5HT1a and 5HT2 receptors, with the symptoms of serotonin toxicity arising from the specific location of the 5HT receptors in the body.[8]

For example, serotonergic projections to the thalamus and cortex result in effects on sleep-wake cycles, mood, thermoregulation, appetite, pain perception, and sexual function. Excess 5-HT in these pathways causes the mental status changes, confusion, agitation, ataxia, and fever associated with SSRI toxicity and SS. Toxicity of descending pathways to the brainstem and medulla results in hyperreflexia, myoclonus, and tremor. Seizures are rare in SSRI overdose, with the exception of citalopram, which has an increased risk of inducing seizures in both adults and children.[14, 15]

Autonomic nervous system effects include diaphoresis, mydriasis, hypertension, tachycardia, hyperthermia, piloerection, and muscular rigidity.

Cardiovascular effects most commonly include sinus tachycardia, flushing, hypertension, and in rare cases, hypotension. Dose-dependent QT prolongation has been reported with citalopram (Celexa).[15, 16] Because of the risk for QT prolongation, revised prescribing information was announced in August 2011.[17] Citalopram is contraindicated in individuals with congenital long QT syndrome, and the dose should not exceed 40mg daily.[18]

Due to the high levels of serotonin in gastric and intestinal mucosal enterochromaffin cells, the most common minor adverse effects of SSRI therapy are gastrointestinal; eg, abdominal cramping, nausea, and diarrhea. SSRIs have also been shown to moderately increase the risk of upper gastrointestinal bleeding.[19]

Epidemiology

Occurrence in the United States

Data from the 2013 Annual Report of the American Association of Poison Control Centers' National Poison Data System (AAPCC-NPDS) revealed approximately 2.2 million toxic exposures and 2,113 fatalities.[20] Antidepressants were involved in 4.2% of all exposures, ranking 5th for the most frequently cited substance class. SSRIs were mentioned in 2.2% of all exposures, accounting for 47,336 cases.

Of SSRI exposures without co-ingestion, 50% did not develop any signs or symptoms and 32% had a minor, self-limiting reaction. Moderate effects necessitating treatement were present in 17% of exposures, while 1% had a major, life-threatening effect and 0.05% resulted in death.[20]

Age-related demographics

Based on data from identifiable cases, 41% of SSRI exposures occurred in persons 20 years or older with rates comparable in children 5 years or younger (25%) and in teenagers aged 13 to 19 years (28%). The majority of SSRI exposures were unintentional (51%), while 45% were intentional and 4% were due to adverse reactions from prescribed use.

Side effects from SSRIs are not age specific, however elderly persons may be more susceptible by taking a wide variety of medications that alter cytochrome P-450 MFO metabolism.

Prognosis

Most cases fully resolve without residual deficits if supportive care has been provided. The prognosis is generally favorable. Most fatalities occur within the first 24 hours. Patients who remain asymptomatic for 6-8 hours after ingestion are unlikely to require further treatment.

AAPCC-NPDS 2013 data showed that of 2,113 fatalities attributed to toxic exposures, SSRIs were present in 92 of these cases, while only 6 deaths were attributable to SSRI exposure without co-ingestion. SSRIs have a wide therapeutic index, with most fatalaties resulting from co-ingestion of other substances.[20]

Patient Education

All patients started on SSRIs by psychiatrists or primary care physicians should be educated about symptoms of serotonin toxicity and SS.

Patients should be counseled about potential interactions among any medications they take—including over-the-counter medications (particularly dextromethorphan-containing cold remedies), illicit drugs (especially amphetamines, MDMA, cocaine, and mescaline), and herbal dietary supplements/nutraceuticals (eg, St. John's wort, ginseng, and S-adenosyl-methionine)—that might affect the patient's tissue concentrations of serotonin.

 

Presentation

History

Serotonin toxicity is most likely to develop following the initiation of a new serotonergic medication or the increase in dosage of a previously prescribed SSRI.[12]

Symptom onset from SSRI toxicity presents within 2-8 hours after acute ingestion, or it may occur over several days if serotonin syndrome (SS) develops from the initiation of a new therapy or the addition of a second serotonergic agent.

A history of mental illness, particularly affective disorders, and prior suicide attempts should be elicited.

Serotonin syndrome diagnostic criteria

Diagnostic criteria for SS were developed in 1991 by Sternbach et al to assist in diagnosis.[1] The Sternbach criteria include the following:

  • Symptoms coincide temporally with the addition of a serotonergic agent to a patient's regimen or with an increase in the dose of a previously prescribed serotonergic agent

  • At least 3 of the following physical findings are present: agitation, ataxia, diaphoresis, diarrhea, hyperreflexia, mental status changes, myoclonus, shivering, tremor, or hyperthermia

  • A neuroleptic agent has not been recently added to the patient's regimen or increased in dose, if previously prescribed

  • Other etiologies, such as infection, intoxication, metabolic derangements, substance abuse, and withdrawal, have been ruled out

These criteria have been modified over time to account for symptoms associated with more mild cases, but they provide a framework for the history and physical examination to aid in diagnosis.

Newer diagnostic criteria include the Hunter Serotonin Toxicity Criteria, which were established based on single-agent SSRI overdoses, as well as on combinations of serotonergic drugs. This decision rule is based more on the presence of neuromuscular findings (clonus, hyperreflexia, tremor, diaphoresis, hyperthermia) than on altered mental status and was found to have a sensitivity of 84% and a specificity of 97% in predicting SS.[21]

Mild cases of SS, due to vague symptomatology, may often go unrecognized.

Physical Examination

Signs of excess serotonin can range from subtle tremor to frank coma.[22] Mental status changes, autonomic instability, and neuromuscular agitation are the primary findings used to delineate Sternbach's criteria. However, more specific signs and physical findings have become recognized as reliable predictors of serotonin toxicity; several decision rules have been established to help clinicians identify patients with possible SS.

Neuromuscular findings

Neuromuscular findings, such as clonus, hyperreflexia, muscular rigidity, and ataxia, may be present, as well as myoclonic jerks, teeth chattering, and resting tremor. The clonus is spontaneous, inducible, or ocular. Hyperreflexia is often more pronounced in the lower extremities. Muscular rigidity may mask clonus. Among these findings, clonus is the most useful in diagnosing SS.

Mental status findings

Mental status findings may be subtle, including such symptoms as pressured speech, restlessness, and confusion. More severe cases may manifest with agitation, hypomania, coma, or seizures.

Autonomic findings

Autonomic instability includes diaphoresis; hyperthermia, which is exacerbated by prolonged muscular rigidity or seizure activity; tachycardia; mydriasis; and blood pressure lability including hypertension and hypotension. Electrocardiographic changes such as QTc prolongation have been reported specifically in citalopram ingestions.

Peripheral findings

Peripheral findings may include increased gastrointestinal motility (eg, diarrhea or hyperactive bowel sounds), coagulopathy (disseminated intravascular coagulation in severe cases), and increased vascular tone.

Serotonin toxicity versus other toxicities

Physical examination findings are helpful in distinguishing serotonin toxicity from other toxic ingestions (although ingestion of multiple agents in suicide attempts can make physical findings less reliable).

Neuroleptic malignant syndrome, associated with dopamine antagonists, has a slower onset of symptoms than SS and is associated with bradykinesia and "lead-pipe" muscular rigidity, rather than hyperkinesias and tremors.

Anticholinergic toxicity involves dry, erythematous skin; enlarged pupils (mydriasis); decreased bowel sounds; and normal reflexes, in contrast to serotonin toxicity, which includes diaphoresis, increased bowel sounds, diarrhea, and hyperreflexia.

 

DDx

Diagnostic Considerations

Other conditions to be considered include the following:

  • Malignant hyperthermia

  • Delirium tremens

  • Anticholinergic toxicity

  • Antidepressant toxicity

  • Antihistamine toxicity

  • Carbamazepine toxicity

  • Cocaine toxicity

  • MDMA toxicity

  • Methamphetamine toxicity

  • MAOI toxicity

  • Neuroleptic agent toxicity

  • Phencyclidine toxicity

  • Sympathomimetic toxicity

Differential Diagnoses

 

Workup

Approach Considerations

Diagnosis of serotonin toxicity begins with a detailed history of the patient's medications, of changes to regimen, and of possible overdose; queries into the availability of serotonergic drugs; and a careful physical examination. Laboratory tests used in the diagnosis of serotonin toxicity may include the following:

  • Serum and urine toxicology screen - Opiates/opioids (meperidine), salicylates, acetaminophen, TCAs, amphetamines, phencyclidine (detection of dextromethorphan by cross-reactivity), and cocaine

  • Total creatine phosphokinase

  • Urine myoglobin

  • Basic electrolytes, including calcium, magnesium, and phosphorus levels, as well as lactate and ketone levels - to evaluate for metabolic acidosis

  • Blood urea nitrogen (BUN) and creatinine levels

  • Serum pH level

  • Liver function tests

  • Complete blood count and blood cultures if febrile

  • Prothrombin time/activated partial thromboplastin time in severe cases; disseminated intravascular coagulation panels, if necessary

  • Pregnancy testing, if indicated

  • Electrocardiography - To determine rhythm, morphology, and intervals, particularly in suspected co-ingestions

Imaging studies

Imaging studies include chest radiograph after intubation or in any patient with hypoxia or aspiration. Head computed tomography (CT) scanning can be conducted in any patient with suspected trauma, new-onset seizures, or hypertension and localizing neurologic findings

Procedures

Intubation should be considered in any unstable patient or any patient with altered mental status who cannot protect his or her airway. Lumbar puncture is indicated in any patient with fever and altered mental status.

 

Treatment

Approach Considerations

All patients with significant ingestions requiring intubation or vasopressors, those with a temperature higher than 40⁰C, or those with electrocardiographic changes/dysrhythmias should be admitted to an intensive care unit. Moderate toxicity can be safely observed in the hospital for 24 hours, and mild cases can be safely discharged (if asymptomatic) from the emergency department once cleared by Psychiatry in cases of intentional overdose and after 6 to 8 hours of observation.

Inpatient care should include ongoing fluid resuscitation and appropriate treatment of rhabdomyolysis, disseminated intravascular coagulation, and renal or hepatic dysfunction, as well as psychiatric evaluation.

Symptomatic patients with citalopram/escitalopram overdose may require admission to a monitored bed for 24 hours because of the risk of delayed toxicity, which can cause prolonged QTc interval and consequent cardiac dysrhythmias (eg, torsades de pointes).

Consultations

The following consultations can aid in patient care:

  • Medical toxicologist

  • Poison Control Center at (800) 222-1222 (US and territories only)

  • Psychiatrist

Prehospital Care

Prehospital care includes airway management and arrhythmia treatment per advanced cardiac life support (ACLS) protocols; consider naloxone, 50 mL of D50W, and thiamine 100 mg IV, as well as a fingerstick glucose level for altered mental status. If given, naloxone should be gradually titrated, starting with 0.05 or 0.1 mg, and repeated if needed, to avoid rapid precipitation of opioid withdrawal.

Of critical importance is obtaining history from any bystanders or family members and collecting ancillary materials, such as pills, empty pill bottles or medication packets, and suicide notes. Out-of-hospital management guidelines are available from the AAPCC.[23]

Emergency Department Care

As with all care in the emergency department, immediate evaluation and stabilization of the patient's airway, breathing, and circulation is paramount, even without knowledge of the ultimate diagnosis. Treatment of serotonin syndrome (SS) is primarily supportive. The initial severity of presentation helps guide appropriate emergency department care.

Mild cases

Care for mild cases includes a review of laboratory results, as indicated; the administration of IV fluids for dehydration/hypotension, provision of benzodiazepines (for agitation/restlessness), and avoidance of all serotonergic medications.

Moderate cases

Treat hyperthermia with cooling blankets, fans, ice packs, and IV fluids. Antipyretics are not indicated, as the mechanism for temperature alteration is centrally mediated. Administer activated charcoal if a potentially lethal amount or combination of proserotonergic agents has been ingested and if the presentation is within 1 to 2 hours. Treat neuromuscular abnormalities with benzodiazepines.

Severe cases

Patients with hyperthermia, depressed mental status, and vital sign abnormalities should be treated aggressively. All patients should be treated as above, with the addition of airway protection and ventilation if needed. Paralysis and mechanical ventilation may be necessary to avoid worsening muscle rigidity and increasing hyperthermia in any patient with a temperature higher than 41⁰C.

Patients with severe hyperthermia that is unresponsive to aforementioned measures should be cooled as quickly as possible, to prevent development of disseminated intravascular coagulation and multiorgan failure. Avoid succinylcholine as a paralytic in any patient with possible rhabdomyolysis to prevent the development of hyperkalemia.

Severely ill patients can be treated pharmacologically with 5HT antagonists, such as cyproheptadine.[24, 25] Although the drug’s efficacy has not been established in randomized clinical trials, it has shown benefit in animal models and case reports. It is available only in oral form, which can be crushed and infused via nasogastric tube at a dose of 4 mg every hour for 3 doses. Caution should be exercised in hyperthermic patients, because cyproheptadine has anticholinergic properties and theoretically can worsen hyperthermia.

Autonomic instability with episodes of hypertension and/or tachycardia requires treatment with short-acting agents amenable to titration, such as nitroprusside and esmolol.

Deterrence and Prevention

Patients taking SSRIs and MAOIs should be cautioned about taking over-the-counter medications or supplements with serotonergic activity. They should be closely monitored if dosages are adjusted or medications are added to their pharmacotherapeutic regimen.

Patients who require ongoing treatment with a serotonergic agent should be restarted on or introduced to serotonergic medications gradually in the future (after a wash-out period) if they have developed serotonin syndrome. They should report a serotonin syndrome reaction to all healthcare providers in the future.

A minimum of 2 weeks should elapse between termination of an SSRI or MAOI and initiation of a new one. Drugs with a longer half-life (ie, fluoxetine) require up to 5 weeks of wash out. Elderly patients and those taking liver MFOs may require an extended wash-out period as well.

 

Medication

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

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.

Vasodilators

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

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.

 

Questions & Answers

Overview

What are selective serotonin reuptake inhibitors (SSRIs)?

What is serotonin syndrome (SS)?

What causes serotonin reuptake inhibitor (SSRI) toxicity?

What are the causes of serotonin syndrome (SS)?

Which serotonin-norepinephrine reuptake inhibitors (SNRIs) are associated with serotonin syndrome (SS)?

What is the role of trazodone in the etiology of serotonin syndrome (SS)?

What is the role of bupropion (Wellbutrin) in the etiology of serotonin syndrome (SS)?

Which opioids are associated with serotonin syndrome (SS)?

Which antimicrobial agents are associated with serotonin syndrome (SS)?

What is the pharmacokinetics of selective serotonin reuptake inhibitor (SSRI) toxicity?

What are the complications of selective serotonin reuptake inhibitor (SSRI) toxicity?

What is the role of serotonin in the pathogenesis of selective serotonin reuptake inhibitor (SSRI) toxicity?

What causes serotonin syndrome (SS)?

What is the importance of medication history in determining the etiology of selective serotonin reuptake inhibitor (SSRI) toxicity?

What is the cause of the multiple signs and symptoms of selective serotonin reuptake inhibitor (SSRI) toxicity?

What are the mechanisms of serotonin increase in selective serotonin reuptake inhibitor (SSRI) toxicity?

What are the physiologic manifestations of serotonin syndrome (SS)?

What are the autonomic nervous system effects of selective serotonin reuptake inhibitor (SSRI) toxicity?

What are the cardiovascular system effects of selective serotonin reuptake inhibitor (SSRI) toxicity?

What are the GI effects of selective serotonin reuptake inhibitor (SSRI) toxicity?

What is the incidence of selective serotonin reuptake inhibitor (SSRI) toxicity in the US?

How does the incidence of selective serotonin reuptake inhibitor (SSRI) toxicity vary by age?

What is the prognosis of selective serotonin reuptake inhibitor (SSRI) toxicity?

What causes fatality in selective serotonin reuptake inhibitor (SSRI) toxicity?

What should be included in patient education about selective serotonin reuptake inhibitor (SSRI) toxicity?

Presentation

When is selective serotonin reuptake inhibitor toxicity most likely to develop?

What should be the focus of patient history in the evaluation of selective serotonin reuptake inhibitor (SSRI) toxicity?

What are the diagnostic criteria for serotonin syndrome (SS)?

What is the Hunter Serotonin Toxicity Criteria for the diagnosis of selective serotonin reuptake inhibitor (SSRI) toxicity?

What are the signs and symptoms of serotonin syndrome (SS)?

What are the general signs of excess serotonin in selective serotonin reuptake inhibitor (SSRI) toxicity?

What are the neuromuscular findings suggestive of selective serotonin reuptake inhibitor (SSRI) toxicity?

What are the mental status findings suggestive of selective serotonin reuptake inhibitor (SSRI) toxicity?

What are the autonomic findings suggestive of selective serotonin reuptake inhibitor (SSRI) toxicity?

What are the peripheral findings suggestive of selective serotonin reuptake inhibitor (SSRI) toxicity?

How is selective serotonin reuptake inhibitor (SSRI) toxicity distinguished from other toxic ingestions?

How is neuroleptic malignant syndrome distinguished from selective serotonin reuptake inhibitor (SSRI) toxicity?

How is anticholinergic toxicity distinguished from selective serotonin reuptake inhibitor (SSRI) toxicity?

DDX

Which conditions should be included in the differential diagnosis for selective serotonin reuptake inhibitor (SSRI) toxicity?

What are the differential diagnoses for Selective Serotonin Reuptake Inhibitor Toxicity?

Workup

What is the role of lab testing in the diagnosis of selective serotonin reuptake inhibitor (SSRI) toxicity?

What is the role of imaging studies in the workup of selective serotonin reuptake inhibitor (SSRI) toxicity?

Which procedures are used in the workup of selective serotonin reuptake inhibitor (SSRI) toxicity?

Treatment

What are the treatment options for selective serotonin reuptake inhibitor (SSRI) toxicity?

What is included in inpatient care for selective serotonin reuptake inhibitor (SSRI) toxicity?

How is symptomatic citalopram/escitalopram overdose managed?

Which specialist consultations can aid in patient care for selective serotonin reuptake inhibitor (SSRI) toxicity?

Which organization has issued guidelines for prehospital management of selective serotonin reuptake inhibitor (SSRI) toxicity?

What is included in prehospital care for selective serotonin reuptake inhibitor (SSRI) toxicity?

What is the initial emergency department (ED) care for selective serotonin reuptake inhibitor (SSRI) toxicity?

What is included in the emergency department (ED) care of mild selective serotonin reuptake inhibitor (SSRI) toxicity?

What is included in the emergency department (ED) care of moderate selective serotonin reuptake inhibitor (SSRI) toxicity?

What is the protocol for severe emergency department care for patients with selective serotonin reuptake inhibitor toxicity?

How is severe hyperthermia in selective serotonin reuptake inhibitor (SSRI) toxicity managed?

What are the pharmacological treatment options for severe selective serotonin reuptake inhibitor (SSRI) toxicity?

What is the role of nitroprusside and esmolol in the treatment of selective serotonin reuptake inhibitor (SSRI) toxicity?

How is selective serotonin reuptake inhibitor (SSRI) toxicity prevented in patients taking monoamine oxidase inhibitors (MAOIs)?

How is selective serotonin reuptake inhibitor (SSRI) toxicity prevented in patients who require ongoing treatment with a serotonergic agent?

How is selective serotonin reuptake inhibitor (SSRI) toxicity prevented when switching medications?

Medications

What are the pharmacologic treatment options for selective serotonin reuptake inhibitor (SSRI) toxicity?

Which medications in the drug class Neuromuscular Blockers, Depolarizing are used in the treatment of Selective Serotonin Reuptake Inhibitor Toxicity?

Which medications in the drug class Vasodilators are used in the treatment of Selective Serotonin Reuptake Inhibitor Toxicity?

Which medications in the drug class Anxiolytics, Benzodiazepines are used in the treatment of Selective Serotonin Reuptake Inhibitor Toxicity?

Which medications in the drug class Antidotes, Other are used in the treatment of Selective Serotonin Reuptake Inhibitor Toxicity?