SSRI Toxicity

Introduction

SSRIs are frequently prescribed and are often taken in overdose. Generally these agents have a good safety profile and overdoses can be managed well with appropriate supportive care. Serotonin toxicity is possible with a large single ingestion, but is more common with a combination of serotonergic agents. Serotonin toxicity is potentially life threatening and is discussed separately in the Serotonin Toxicity module. The SSRIs which are available in Australia are citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline.

Toxicokinetics1

SSRIs are well absorbed and have a large volume of distribution, with significant protein binding. They undergo hepatic metabolism. They have long half lives and active metabolites. They take many weeks to reach a steady state.

Risk Assessment

Symptoms in overdose are typically mild and are manifestations of serotonin excess, including nausea, vomiting and dizziness. Uncommonly serotonin toxicity can occur and should be actively looked for.

Citalopram and escitalopram are special cases as they are associated with bradycardia and QT prolongation. An ECG must be performed in all patients presenting following a citalopram or escitalopram ingestion.

Management

Supportive care is the mainstay of therapy. Management of serotonin toxicity is considered elsewhere.

Decontamination

Given the relatively benign course of an isolated SSRI ingestion, activated charcoal is typically not indicated. However given the potential cardiotoxicity of citalopram and escitalopram, activated charcoal is recommended if the patient consents.2

Activated Charcoal in Citalopram Overdose2

Citalopram SDAC table

For escitalopram substitute 300mg of escitalopram for 600mg citalopram and 400mg of escitalopram for 1000mg citalopram.  All citalopram and escitalopram overdoses should be discussed with the toxicology team to determine parameters for cardiac monitoring if necessary.

Supportive Measures includes nursing in a quiet environment, with attention to symptom control such as anti-emetics and benzodiazepines.

Disposition

The majority of patients are suitable for discharge from a medical perspective if they are asymptomatic 4 to 6 hours following the overdose.  Symptoms of serotonergic excess warrant a short stay admission under the toxicology unit until symptoms settle.

Additional Information

  • Mirtazapine is a unique newer antidepressant with serotonin reuptake inhibition as well as ?2 receptor antagonism, leading to increased neuronal noradrenaline and serotonin. In overdose mirtazapine is relatively benign causing a tachycardia and mild sedation.3,4 Interestingly it has serotonin receptor blocking action and some use it as a treatment for serotonin toxicity.

Further Reading

References

  1. Nelson L et al. Goldfrank’s Toxicologic Emergencies. 9th 2010. McGrawHill Medical: Sydney.
  2. Isbister, G. K., and V. V. Kumar. “Indications for Single-Dose Activated Charcoal Administration in Acute Overdose.” Curr Opin Crit Care 17, no. 4 (2011): 351-7.
  3. Waring WS, Good A and Bateman DN. “Lack of significant toxicity after mirtazepine overdose: A five year review of cases admitted to a regional toxicology unit.” Clin Tox 2007; 45:45-50
  4. Berling I and Isbister G. “Mirtazepine overdose is unlikely to cause major toxicity.” Clin Toxicol 2013; DOI: 10.3109/15563650.201