Overdose and Treatment of Quetiapine Ingestions

P H A R M / T O X C O R N E R

Authors: Sara Brown, RNII, and Rachel Sweeney, RN,

BSN, CSPI

Section Editor: Allison A. Muller, PharmD, D.ABAT

Sara Brown, Cincinnati Drug and Poison Information Center,Cincinnati, Ohio.

Rachel Sweeney, Cincinnati Drug and Poison Information Center,Cincinnati, Ohio.

For correspondence, write: Sara Brown, Cincinnati Drug and PoisonInformation Center, 3333 Burnet Ave, ML 9004, Cincinnati, OH45229; E-mail: Sara.Brown@cchmc.org.

J Emerg Nurs 2007;33:582-4.

Available online 22 October 2007.

0099-1767/$32.00

Copyright n 2007 by the Emergency Nurses Association.

doi: 10.1016/j.jen.2007.09.002

582

Earn Up to 8 CE Hours. See page 591.

uetiapine, marketed as SeroquelR, is an atypical

Qantipsychotic medication that is FDA-approved

for the treatment of bipolar disorder and schizo-

phrenia, and is used off-label for other types of psychiatric

disorders. According to the National Institute of Mental

Health (NIMH), about 5.7 million American adults or

about 2.6% of the population age 18 and older are living

with bipolar disorder.1 The NIMH describes schizophre-

nia as a ‘‘chronic, severe, and disabling brain disorder that

affects about 1.1% of the US population age 18 and

older.’’1 Because bipolar disorder and schizophrenia are

chronic and debilitating life-long illnesses, suicide attempts

are not infrequent occurrences.

Case 1

A 35-year-old male presents to the emergency department

with a decreased level of consciousness. He admits that he

took what was left in his quetiapine bottle with no other

co-ingestants. He has no idea how many he took. Initial

exam shows he is hypotensive with a blood pressure of

85/50 mm Hg and tachycardic with a heart rate of 122 bpm.

The patient is drowsy, but will arouse with painful stimuli.

Initial EKG shows slight widening of the QRS complex

(110 milliseconds). Patient was given sodium bicarbonate,

intravenous f luids, and admitted to a f loor where he could

be monitored on a continuous cardiac monitor.

Effects in Overdose

As an ED nurse, it is important to know that an overdose

of quetiapine can cause multiple types of cardiovascular

effects including tachycardia, hypotension, and an increase

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P H A R M / T O X C O R N E R / B r o w n a n d S w e e n e y

in the QRS and QTc intervals.2,3 Anticholinergic effects

are also possible during an over dosage of quetiapine

(constipation, decreased bowel sounds, and dry mouth).2,3

Quetiapine also causes central nervous system depression

and delirium.2,3 Infrequently, in severe overdoses, it can

cause extrapyramidal effects and seizures.2 Laboratory data

may show hypokalemia and rhabdomyolysis.2

Treatment

The cornerstone of treatment for an overdose of quetiapine

includes supportive care and continuous cardiac monitor-

ing. Activated charcoal can be given for initial decontami-

nation.3 Activated charcoal should be given with caution

in any patient who is drowsy and unable to protect his/

her airway.

EKG monitoring is necessary for a quetiapine over-

dose patient. QRS widening may be corrected with sodium

bicarbonate.3 QTc prolongation requires no specific treat-

ment other than correction of potential contributing causes

such as hypokalemia and hypomagnesemia. Torsades de

pointes should be treated with intravenous magnesium sul-

fate, taking care to prevent hypotension. Sinus tachycardia

should not be treated unless it is associated with active

ischemia, which is uncommon, but may complicate over-

doses in patients with existing coronary disease.4 Hypoten-

sion can be treated with f luids and vasoconstrictors such

as norepinephrine or phenylephrine.3 Because quetiapine

is a potent a1 receptor antagonist, vasopressors with h-2

activity such as epinephrine or isoproterenol may worsen

quetiapine-induced hypotension.4 Seizures are possible as the

seizure threshold is lowered.4 Seizures are generally short-

lived, however, and often require no pharmacologic treat-

ment. Multiple or refractory seizures should prompt a search

for other causes. When treatment is necessary, benzodiaze-

pines such as lorazepam or diazepam generally suffice, al-

though phenobarbital may be necessary.4

Efforts to enhance elimination with hemodialysis or

multi-dose charcoal have not been shown to be effective

in overdose.3 With good supportive care, effects from

quetiapine overdose typically resolve in 24 hours.2

Follow Up

Fifteen hours after the ingestion, the patient was still

being observed on a telemetry unit. His symptoms seemed

December 2007 33:6

to be improving. He was still receiving intravenous f luids,

but did not require vasopressors. He was more awake but

still drowsy. His blood pressure had normalized, and he

was still slightly tachycardic at 105 bpm. EKG showed

his QRS was now normal, and a continuous sodium bicar-

bonate infusion had been discontinued. Labs showed acet-

aminophen was negative, and his serum potassium was

normal. Although quetiapine may cause a false positive for

tricyclic antidepressants on a urine antibody drug screen,

this was not the case in our patient.

At the 25-hour mark, the patient was asymptomatic

with normal vital signs and normal sinus rhythm. The

patient was completely awake and alert, and he was dis-

charged to a psychiatric facility.

Deaths Associated With Quetiapine Overdose

Quetiapine represents a substantial improvement in the

treatment of schizophrenia and related disorders. It is con-

sidered to have a favorable adverse effect profile relative to

traditional antipsychotics.5 Nonetheless, people have died

as a result of quetiapine overdose. Quetiapine overdose alone

or in combination with other medications has resulted in

QTc prolongation. This can potentially lead to torsades

de pointes triggering ventricular dysrhythmias and cardiac

arrest.6 Another potentially fatal effect with quetiapine

overdose is respiratory depression. In large overdoses pa-

tients may require intubation. Loss of consciousness with

need for airway protection in major overdoses warrants

close observation in an intensive care setting.7 Toxico-

logic exposures and fatalities associated with atypical anti-

psychotics (including quetiapine) continue to increase in

the United States with 32,422 exposures and 72 deaths

in 2003.6

Three cases of suicidal overdoses involving quetiapine

were presented by Loralie J. Langman from the Provincial

Toxicology Center of British Columbia, Canada.8 In the

first 2 cases, quetiapine was considered to be the cause of

death and other drugs ingested were not considered to be

contributory.8 The third case involved co-ingestants but

the concentration of quetiapine found in femoral blood

was significantly elevated above the therapeutic range

(0.1 to 1.0 mg/L).8 The concentrations of quetiapine in

all 3 cases were 6 to 16 times greater than the upper

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P H A R M / T O X C O R N E R / B r o w n a n d S w e e n e y

reported therapeutic range.8 In all 3 cases, the patients were

found dead in their homes.8

Range of toxicity for quetiapine is highly variable.

Deaths have occurred with therapeutic doses as well as

with massive ingestions.5 Co-ingestion of other agents, par-

ticularly drugs with similar metabolic pathways, may in-

crease toxicity.5 For example, some medications that can

increase quetiapine serum concentration include ketocona-

zole, f luvoxamine, protease inhibitors, and erythromycin.6

As more physicians prescribe quetiapine, prevention and

management of these overdoses become more significant.

Conclusion

Quetiapine is an atypical antipsychotic medication that is

often used for chronic treatment of bipolar disorder and

schizophrenia. Effects of overdose can become severe, but

can be managed. Severe overdoses that result in death

typically involve patients who are found unconscious with

respiratory depression and have severe cardiac effects. With

early intervention, supportive care, and close monitoring, a

quetiapine-poisoned patient typically recovers in 24 hours.

Acknowledgments

We would like to thank G. Randall Bond, MD, FACMT, andAlysha Behrman RN, BSN, CSPI for review of this article.

REFERENCES1. National Institute of Mental Health. Available at: http://

www.nimh.nih.gov/healthinformation. Accessed May 2007.

2. Klasco RK, editor. Quetiapine (management/treatment protocol).PoisindexR System. Thomas MICROMEDEX series, copy-right 1974-2007 Vol. 132, expires June 2007.

3. Lackey GD. Antipsychotic drugs, including phenothiazines.In: Olsen KR, editor. Poisoning and drug overdose. New York:McGraw Hill; 2004. p. 107-109, 401.

4. Juurlink D. Antipsychotics. In: Flomenbaum M, GoldfrankL, Hoffman RS, Howland MA, Lewin N, Nelson L, editors.Goldfrank’s toxicologic emergencies. 8th ed. New York: McGrawHill; 2006. p. 1043.

5. Trenton A, Currier G, Zwemer F. Fatalities associated withtherapeutic use and overdose of atypical antipsychotics. CNSDrugs 2003;17:307-24.

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6. DuBois D. Toxicology and overdose of atypical antipsychoticmedications in children: does newer necessarily mean safer? CurrOpin Pediatr 2005;17:227-33.

7. Harmon TJ, Benitez JG, Krenzelok EP, Cortes-Belen E. Loss ofconsciousness from acute quetiapine overdosage. J Toxicol ClinToxicol 1998;36:599-602.

8. Langman LJ, Kaliciak HA, Carlyle S. Fatal overdoses associatedwith quetiapine. J Anal Toxicol 2004;28:520-5.

Submissions to this column are welcomed and encouraged. Submis-sions may be sent to:

Allison A. Muller, PharmD, D.ABATThe Children’s Hospital of Philadelphia, 34th and Civic CenterBlvd, Philadelphia, PA 19104

215 590-2004 . mullera@email.chop.edu

OURNAL OF EMERGENCY NURSING 33:6 December 2007