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    Venlafaxine (Effexor XR) and Desvenlafaxine (Pristiq) Overdoses

    Toxicology

    Last Updated Oct 30, 2018
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    Context

    Venlafaxine (and desvenlafaxine) are commonly prescribed antidepressants.
    Large overdoses can result in QRS prolongation, ventricular dysrhythmias, delayed onset seizures, and death. Only the extended release formulation of each drug is available in BC.

    Reccommend consult with BC Drug and Poison Information Centre at 604-682-5050, 1-800-567-8911, or dpic.org.

    Signs and Symptoms

    • Common: Drowsiness, agitation, seizures, tachycardia (usually sinus), mild hypertension, and serotonin syndrome
    • Less common: Serious ventricular dysrhythmias and coma
    • Uncommon: Severe hypotension
    • ECG changes can include:
      • QRS widening,
      • Right axis deviation,
      • Non-specific ST or T wave changes,
      • LBBB or RBBB
      • Prolonged QTc interval.
    • Ventricular dysrhythmias after large overdoses can include ventricular tachycardia, ventricular fibrillation, torsades de pointes, and asystole.
    • Seizures are usually generalized, may be single or multiple, but are usually abrupt in onset and short in duration.

    Typical Course

    • Onset usually within 6 hours. XR formulation can cause delayed seizures up to 19 hours post exposure.
    • Symptoms generally resolve over 24-36 hours.

    Mechanism of Toxicity

    • Cardiac toxicity may involve sodium channel blockage.
    • Blockage of uptake of serotonin and norepinephrine may produce serotonin syndrome.
    • Serotonin Syndrome:
      • Symptoms may include hyperthermia, agitation, increased reflexes, tremor, myoclonus, dilated pupils, sweating, shivering, diarrhea
      • Severe cases progress to seizures, hyperthermia, rhabdomyolysis, disseminated intravascular coagulopathy, ventricular dysrhythmias and respiratory arrest.
      • Hyperreflexia and clonus (spontaneous, inducible, ocular) are the most common diagnostic features.

    Toxic Dose

    • Not established.
    • Fatalities in adults with ingestions of as little as 4.2 grams.
    • Ingestions < 8 grams can result in drowsiness, seizures, tachycardia, hypotension, widened QRS interval, QTc prolongation, and coma.
    • Ingestions > 8 grams may cause ventricular dysrhythmias. Pediatric data is limited.

    Diagnostic Process

    • Serum levels are not readily available and do not correlate with toxicity or outcome.

    Clinical Pitfalls

    • XR formulation is associated with delayed onset seizures.
    • False positive urine immunoassay for phencyclidine (PCP) has been reported with venlafaxine overdose.

    Recommended Treatment

    General:

    • Asymptomatic cases should have continuous cardiac monitoring of vital signs for 18 hours. ECG should be obtained on admission and prior to discharge. Symptomatic cases should be monitored for 12 hours after resolution of symptoms.
    • Activated charcoal may be useful longer than the usual one hour after ingestion of XR preparations. Consider the benefits versus the risks on a case-by-case basis.
    • Protect airway and assist ventilation as needed.
    • Monitor vital signs hourly and electrolytes every 2 hours initially. Monitor blood gases q2 hourly in symptomatic patients – at least initially.

    Agitation, tremor, hyperreflexia, myoclonus, and seizures:

    • Should be treated with IV benzodiazepine: seizures may require high doses of benzodiazepines – such as 10 mg aliquots of IV Diazepam q 10 minutes (Rosens) may be required.
    • Seizures refractory to high dose benzodiazepines should be treated with propofol or barbiturates.
    • High doses of benzodiazepines cause respiratory depression requiring airway management.

    Management of Serotonin Syndrome:

    • Control rigidity, myoclonus or seizures with IV benzodiazepines; high doses may be required. Persistent or refractory symptoms may require treatment with propofol, or barbiturates.
    • Monitor vital signs including body temperature hourly. Monitor serum electrolytes, glucose, renal function myoglobin, creatine kinase and ECG. In severe cases monitor LFTs, INR and blood gases initially q 2hours.
    • Treat hyperthermia aggressively with external cooling (ice packs to groin and axilla, cool mist and fan). Hyperthermic patients (>41.0oC) should be treated with above therapies and neuromuscular paralysis and intubation.
    • Drugs that block serotonin receptors may improve serotonin syndrome. Most clinical experience is in patients with mild to moderate symptoms.
    • Cyproheptadine (Periactin®)
      • Adult: 8-16 mg orally, repeat as required up to maximum of 32 mg/day.
      • Child: 0.25 mg/kg/day divided every 6 hours (maximum 12 mg day).

    Hypotension:

    • Hypotension unresponsive to IV fluids should be monitored closely. Vasopressors may be required (many would recommend norepinephrine with a dosing range of 2-20 micrograms per minute titrated to effect).

    Hypertension:

    • Hypertension rarely requires treatment.

    Cardiac toxicity:

    • QTc prolongation should be monitored. Measure serum potassium, magnesium and calcium and correct as necessary.
    • Wide complex tachycardia (QRS > 0.1 sec) may respond to IV sodium bicarbonate boluses (2-3 ampoules or 1-2 mEq/kg); repeat boluses every 3-5 minutes until QRS interval narrows or until serum pH reaches 7.55.
    • Ventricular dysrhythmias may respond to sodium bicarbonate boluses.

    IV lipid emulsion therapy:

    • IV lipid emulsion therapy may be considered in patients refractory to standard resuscitation measures or who are rapidly deteriorating despite therapy.

    Hemodialysis:

    • Hemodialysis is not effective.

    Criteria For Hospital Admission

    • Dysrhythmias, hypotension, and seizures all need to be admitted to an ICU.

    Criteria For Transfer To Another Facility

    • If patient requires ICU care. Consult BC DPIC for further discussions.

    Consult

    • BC Drug and Poison Information Centre at 604-682-5050, 1-800-567-8911, or dpic.org.

    Criteria For Safe Discharge Home

    • After observation periods have been met and the patient’s psychiatric condition has been treated if the overdose was intentional.

    Quality Of Evidence?

    Justification

    Case reports and case series.

    Low

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