Ketiapin

Clinical Effects:

QUETIAPINE
  • USES: Quetiapine is an atypical antipsychotic drug and is used in schizophrenia and bipolar disorders. EPIDEMIOLOGY: Poisoning with quetiapine is common. Deaths are reported but are rare and usually due to a polypharmacy ingestion. PHARMACOLOGY: Quetiapine is mainly an antagonist at the serotonin receptor 2 (5-HT2) and has only minor antagonist effects on D2 dopamine receptors. In overdose, quetiapine exhibits antimuscarinergic, antihistamine (H1), and antiadrenergic (alpha 1) effects. TOXICOLOGY: Quetiapine overdose is mainly associated with CNS depression and anticholinergic effects. In most cases, sinus tachycardia is observed. Although quetiapine is associated with prolongation of the corrected QT interval (QTc), torsade de pointes (TdP) has not been documented. MILD TO MODERATE POISONING: Dry mouth, constipation, somnolence, dizziness, and mild sinus tachycardia may be observed. SEVERE POISONING: Marked CNS depression, signs of anticholinergic poisoning, such as pronounced sinus tachycardia and urinary retention. Seizures and/or myoclonic jerks may be observed. Mild hypotension occurs but usually responds promptly to fluid resuscitation. Increased serum liver enzymes may also occur. QTc prolongation is often observed, although ventricular dysrhythmias have not been documented. Respiratory depression may occur following massive overdoses due to CNS depression. ADVERSE EFFECTS: Somnolence, dizziness, sinus tachycardia, palpitations, and orthostatic hypotension can develop. Dry mouth, constipation, urinary retention, dyspepsia, elevated liver enzymes are also often reported.

Range of Toxicity:

QUETIAPINE
  • TOXIC DOSE: SUMMARY: A dose of more than 100 mg is potentially toxic in a drug naive child less than 12 years old. A dose of more than 125 mg is potentially toxic in a drug naive child aged 12 years or greater. In children on chronic quetiapine therapy an acute ingestion of more than 5 times their current single dose (not daily dose) is potentially toxic. ADULT: An adult died after ingesting 10.8 g of quetiapine, but other patients have survived overdoses of up to 36 g. PEDIATRIC: An 11-year-old developed relatively minor symptoms following an overdose of 1300 mg. Acute dyskinesia, myoclonus, and akathisia developed in a 13-year-old boy that intentionally abused quetiapine via insufflation; he recovered uneventfully. THERAPEUTIC DOSE: BIPOLAR: Initial dose: 50 mg orally once daily, increase the dosage up to 800 mg daily in 2 divided doses in bipolar maintenance therapy. MANIC BIPOLAR I DISORDER: Usual effective dosage range is 400 to 800 mg/day; maximum daily dose is 800 mg. PEDIATRIC: MANIC BIPOLAR I DISORDER: 10 to 17 years: Initial dose: 50 mg orally on day 1. Dosage adjustments should be done in increments of not more than 100 mg/day to the recommended dosage range of 400 to 600 mg/day. Maximum dose: 600 mg.

Treatment:

QUETIAPINE
  • Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Primarily supportive care; activated charcoal may prevent or shorten the duration of symptoms in patients presenting shortly after ingestion of a significant amount of the drug. MANAGEMENT OF SEVERE TOXICITY: Consider activated charcoal if a patient presents early after ingestion. If significant CNS depression occurs, perform orotracheal intubation for airway protection before giving charcoal. Administer benzodiazepines to treat seizures. Mild hypotension can be treated with normal saline. A Foley catheter may be necessary in case of urinary retention.
  • Decontamination: PREHOSPITAL: Decontamination is not recommended because of the potential for somnolence and seizures. HOSPITAL: Consider activated charcoal after a recent substantial ingestion and if the patient is able to protect their airway. Quetiapine overdose is rarely life-threatening; gastric lavage is generally not indicated.
  • Airway management: Perform early orotracheal intubation in a patient with signs of severe intoxication (marked CNS depression, seizures).
  • Antidote: There is no antidote for quetiapine poisoning.
  • Monitoring of patient: Monitor vital signs and mental status. Quetiapine plasma levels are not rapidly available or clinically useful. No specific lab work is needed in most patients. Obtain an ECG and institute continuous cardiac monitoring in a patient with moderate to severe toxicity. Monitor creatinine phosphokinase levels in a patient with prolonged CNS depression, myoclonus or seizures.
  • Hypotensive episode: Mild hypotension can be treated with IV NS at 10 to 20 mL/kg. Consider norepinephrine or phenylephrine, if hypotension persists.
  • Drug-induced dystonia: ADULT: Benztropine 1 to 2 mg IV or diphenhydramine 1 mg/kg/dose IV over 2 minutes. CHILD: Diphenhydramine 1 mg/kg/dose IV over 2 minutes (maximum 5 mg/kg/day or 50 mg/m(2)/day).
  • Priapism: Priapism may result following a quetiapine overdose due to alpha-adrenergic blockade. An immediate urological consult is necessary. Clinical history should include the use of other agents (ie, antihypertensives, antidepressants, illegal agents) that may also be contributing to priapism. In a patient with ischemic priapism the corpora cavernosa are often completely rigid and the patient complains of pain, while nonischemic priapism the corpora are typically tumescent, but not completely rigid and pain is not typical. Aspirate blood from the corpus cavernosum with a fine needle. Blood gas testing of the aspirated blood may be used to distinguish ischemic (typically PO2 less than 30 mmHg, PCO2 greater than 60 mmHg, and pH less than 7.25) and nonischemic priapism. Color duplex ultrasonography may also be useful. If priapism persists after aspiration, inject a sympathomimetic. PHENYLEPHRINE: Dose: Adult: For intracavernous injection, dilute phenylephrine with normal saline for a concentration of 100 to 500 mcg/mL and give 1 mL injections every 3 to 5 minutes for approximately 1 hour (before deciding that treatment is not successful). For children and patients with cardiovascular disease: Use lower concentrations in smaller volumes. NOTE: Treatment is less likely to be effective if done more than 48 hours after the development of priapism. Distal shunting (NOT first-line therapy) should only be considered after a trial of intracavernous injection of sympathomimetics.
  • Enhanced elimination procedure: There is no role for repeat-dose activated charcoal. Hemodialysis is not useful based on the large volume of distribution.
  • Patient disposition: HOME CRITERIA: Children less than 12 years of age who are naive to quetiapine can be observed at home following an unintentional ingestion of 100 mg or less and are only experiencing mild sedation. All patients, 12 years of age or older, who are naive to quetiapine, can be observed at home following an unintentional ingestion of 125 mg or less and are experiencing only mild sedation. All patients who are taking quetiapine on a chronic basis can be observed at home if they have acutely ingested no more than 5 times their current single dose (not daily dose) of quetiapine. OBSERVATION CRITERIA: Any patient with a deliberate ingestion or more than minor symptoms should be referred to a healthcare facility. Children less than 12 years of age who are naive to quetiapine should be referred to a healthcare facility following an unintentional ingestion of more than 100 mg. All patients, 12 years of age or older, who are naive to quetiapine should be referred to a healthcare facility following an unintentional ingestion of more than 125 mg. All patients who are taking quetiapine on a chronic basis should be referred to a healthcare facility following an acute ingestion of more than 5 times their current single dose (not daily dose) of quetiapine. Patients should be observed for 6 hours (or at least 12 hours after ingestion of extended-release formulations) and should be admitted if they remain symptomatic. ADMISSION CRITERIA: Any patient with persistent hypotension, CNS depression, seizures, or myoclonus should be admitted to the hospital. CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in decision making whether or not admission is advisable, managing patients with severe toxicity (CNS depression, seizures) or in whom the diagnosis is not clear.