How to diagnose and manage a sertraline overdose?

Sertraline Overdose: Diagnosis and Management

Initial Assessment and Clinical Presentation

In sertraline overdose, focus on identifying the classic triad of symptoms: somnolence, vomiting, and tachycardia, which are the most common presenting features, though serious toxicity is rare even with large ingestions. 1

Key Diagnostic Features

Most patients with isolated sertraline overdose remain asymptomatic or develop only minor symptoms. The clinical presentation depends on the amount ingested and presence of co-ingestants:

• Isolated sertraline overdose (most common): Somnolence, vomiting, tachycardia, nausea, dizziness, agitation, and tremor are the predominant findings 1, 2
• Asymptomatic presentation: Approximately 40-65% of patients with isolated sertraline overdose develop no symptoms at all 2, 3
• Neurological symptoms: Lethargy, tremor, agitation, confusion, and rarely seizures or coma 1, 2
• Cardiovascular effects: Tachycardia is most common; bradycardia, hypertension, hypotension, QT-interval prolongation, and rarely Torsade de Pointes can occur 1
• Gastrointestinal symptoms: Nausea, vomiting, diarrhea 1, 2

Critical Life-Threatening Complications to Screen For

Serotonin syndrome is the most dangerous complication and must be actively assessed, particularly if the patient is on other serotonergic medications. 4

Assess for the serotonin syndrome triad within 24-48 hours of ingestion:

• Mental status changes: Confusion, agitation, anxiety 4
• Neuromuscular hyperactivity: Tremors, clonus (most specific finding), hyperreflexia, muscle rigidity 4
• Autonomic hyperactivity: Hypertension, tachycardia, arrhythmias, tachypnea, diaphoresis, shivering, vomiting, diarrhea 4
• Advanced symptoms: Fever, seizures, arrhythmias, unconsciousness, rhabdomyolysis 4, 5

Specific Physical Examination Findings

• Check for clonus (spontaneous, inducible, or ocular) - this is the most specific finding for serotonin syndrome 4
• Assess deep tendon reflexes for hyperreflexia 4
• Monitor vital signs continuously for tachycardia, hypertension, fever, and tachypnea 1, 2
• Evaluate mental status for confusion, agitation, or decreased level of consciousness 1, 2

Laboratory and Monitoring Workup

Obtain the following studies in all suspected sertraline overdoses:

• ECG: Monitor for QT-interval prolongation, bundle branch block, bradycardia, and arrhythmias 1
• Continuous cardiac monitoring: Essential for detecting arrhythmias, particularly in the first 24-48 hours 4
• Creatine kinase (CK): Screen for rhabdomyolysis, especially if serotonin syndrome is suspected 5
• Basic metabolic panel: Assess renal function and electrolytes 5
• Liver function tests: Check for hepatotoxicity in severe cases 1

Note: Sertraline plasma concentrations are not clinically useful for acute management, as they do not correlate well with toxicity and results are not available in time to guide treatment 6

Management Algorithm

Immediate Stabilization (First 30 Minutes)

Ensure adequate airway, oxygenation, and ventilation as the absolute first priority. 1

1. Airway management: Secure airway if patient has altered mental status or is at risk for aspiration 1
2. Vital signs: Monitor cardiac rhythm and vital signs continuously 1
3. IV access: Establish for fluid resuscitation and medication administration 1

Gastrointestinal Decontamination

Perform gastric lavage with a large-bore orogastric tube (with appropriate airway protection) only if the patient presents within 1-2 hours of ingestion or is symptomatic. 1

• Do NOT induce emesis - this is contraindicated 1
• Administer activated charcoal (1 g/kg, maximum 50 g) if patient presents within 1-2 hours of ingestion and can protect their airway 1
• Gastric lavage should only be performed soon after ingestion or in symptomatic patients with appropriate airway protection 1

Specific Treatment Based on Clinical Presentation

For Asymptomatic or Mildly Symptomatic Patients

Observe for a minimum of 6 hours with continuous cardiac monitoring, as most symptoms develop within the first 3-4 hours. 2, 3

• Supportive care: IV fluids, antiemetics for nausea/vomiting 1, 2
• Disposition: If patient remains asymptomatic after 6 hours with normal vital signs and ECG, consider discharge with psychiatric follow-up 2, 3
• Pediatric patients: Children with small ingestions (<10 mg/kg) who remain asymptomatic after 4-6 hours can potentially be managed at home with close parental supervision 3

For Moderate to Severe Toxicity

Admit all patients with significant symptoms for 24-hour observation in a monitored setting. 1, 2

• Benzodiazepines: First-line for agitation, tremor, or seizures (lorazepam 1-2 mg IV or diazepam 5-10 mg IV) 5
• Treat seizures: Benzodiazepines are first-line; avoid phenytoin as it may worsen symptoms 1
• Manage arrhythmias: Standard ACLS protocols; avoid QT-prolonging agents 1
• Treat hypertension/tachycardia: Short-acting beta-blockers or benzodiazepines 5

For Suspected Serotonin Syndrome

Immediately discontinue all serotonergic agents and initiate hospital-based treatment with continuous cardiac monitoring. 4

Treatment protocol:

1. Discontinue sertraline and ALL serotonergic medications immediately 4
2. Supportive care: IV fluids, cooling measures for hyperthermia, continuous cardiac monitoring 4
3. Benzodiazepines: For agitation and muscle rigidity (diazepam 5-10 mg IV or midazolam 2-5 mg IV/SC) 5
4. Cyproheptadine: 12 mg PO initially, then 2 mg every 2 hours (maximum 32 mg/day) until symptoms improve 5
5. Severe cases: May require ICU admission, mechanical ventilation, and neuromuscular paralysis for severe hyperthermia and rhabdomyolysis 5
6. Avoid physical restraints: These can worsen hyperthermia and rhabdomyolysis 5

What Does NOT Work

Forced diuresis, dialysis, hemoperfusion, and exchange transfusion are NOT beneficial due to sertraline's large volume of distribution. 1

There is no specific antidote for sertraline overdose. 1

Critical Pitfalls to Avoid

Co-Ingestant Assessment

Always assume multiple drug ingestion until proven otherwise, as 58% of sertraline overdoses involve co-ingestants, most commonly benzodiazepines and alcohol. 2, 7

• Screen for other serotonergic agents: SSRIs, SNRIs, TCAs, tramadol, meperidine, methadone, fentanyl, dextromethorphan, St. John's Wort, MDMA, cocaine, amphetamines 4
• Check for MAOIs: These dramatically increase serotonin syndrome risk (phenelzine, isocarboxazid, moclobemide, isoniazid, linezolid) 4
• Obtain comprehensive drug history: Including over-the-counter medications, herbal supplements, and illicit drugs 4

Misdiagnosis of Serotonin Syndrome

Serotonin syndrome is frequently missed, especially in children, because it can be confused with behavioral activation, neuroleptic malignant syndrome, or anticholinergic toxicity. 5

• Distinguish from behavioral activation: Serotonin syndrome has autonomic instability and neuromuscular findings (especially clonus), while behavioral activation presents primarily with agitation and restlessness 4
• Key differentiating feature: Hyperreflexia and clonus are specific to serotonin syndrome 4

Underestimating Risk in Large Ingestions

Although sertraline has a wide margin of safety, deaths have been reported with very large ingestions (>13.5 grams), and fatalities have occurred with as little as 2.5 grams. 4, 1, 7

• Do not discharge patients with ingestions >2 grams without extended observation 1, 7
• Admit all patients with symptoms for 24-hour monitoring 1, 2

Premature Discharge

Symptoms can develop or worsen within 24-48 hours, particularly serotonin syndrome. 4

• Minimum observation period: 6 hours for asymptomatic patients with isolated sertraline overdose 2, 3
• Extended observation: 24 hours for symptomatic patients or those with co-ingestants 1, 2

Disposition Guidelines

Admit to monitored bed or ICU if:

• Any symptoms of serotonin syndrome 4, 5
• Significant cardiovascular effects (arrhythmias, QT prolongation, hemodynamic instability) 1
• Seizures or altered mental status 1
• Ingestion >2 grams 1, 7
• Co-ingestion with other serotonergic agents or drugs of concern 2, 7

Consider discharge after 6 hours if:

• Isolated sertraline ingestion <2 grams 2, 3
• Completely asymptomatic with normal vital signs and ECG 2, 3
• No co-ingestants identified 2, 3
• Psychiatric evaluation completed and appropriate follow-up arranged 2, 3