Selective Serotonin Reuptake Inhibitor Toxicity Treatment & Management

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


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.