ORIGINAL CONTRIBUTION
Quetiapine Poisoning and Factors Influencing Severity
Elise Peridy, PharmD,* Jean-François Hamel, MD, PhD,† Anne-Lise Rolland, MD,†
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Bénédicte Gohier, MD, PhD,‡ and David Boels, PharmD, PhD*§
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Abstract:
Purpose/Background: Quetiapine is a relatively new atypical antipsy-
chotic with fewer adverse effects. It is increasingly prescribed to patients.
The purpose of this study was to describe the cases of poisoning observed
at the western France Poison Control Centre and identify potential risk fac-
tors that increase the severity of the cases.
Methods: This was a retrospective study of self-poisoning with quetiapine
as reported by the western France Poison Control Centre between 2007
and 2017.
Results: There were 372 cases of quetiapine poisoning. Circumstances are
known in 367 of 372 cases. There were 75 cases of null severity (grade 0),
133 cases of mild severity (grade 1), 85 cases of moderate severity (grade 2),
and 79 cases of high severity (grade 3). Five deaths were listed in this series.
The most commonly observed symptoms were neurological and cardio-
vascular in nature (drowsiness, coma, tachycardia, hypotension). Of
these cases, 79.8% included voluntary ingestions. Among 302 cases
with coagents, the most common coagents were benzodiazepines (56%),
other psychotropic drugs (41%), and antidepressants (37%). An evaluated
ingested dose 1500 mg or greater and 2 or more coagents increase the risk
of severe poisoning. In particular, concomitant ingestion of benzodiaze-
pines and antidepressants with quetiapine was associated with high sever-
ity (odds ratio, 2.478 [confidence interval, 1.3–4.723]; odds ratio, 1.820
[confidence interval, 1.010–3.316]).
Conclusions: Quetiapine may lead to severe poisoning for which there is
currently no specific treatment. Patients and practitioners should be aware
of this when quetiapine is prescribed, particularly when used in combina-
tion with other medications, and in order to deal with cases of poisoning.
Key Words: antipsychotic, Poison Control Centre, poisoning, psychiatric,
quetiapine
(J Clin Psychopharmacol 2019;39: 312–317)
Q uetiapine is an atypical or second-generation antipsychotic
substance. It belongs to the dibenzothiazepine family. It
has been available in immediate release (IR) form in the United
Kingdom since 1997. It has been marketed in extended-release
(XR) form in the United States (Food and Drug Administration)
since 2007. In France, it has been marketed since 2010 (the French
Health Authority [HAS]), has been available in generic form
since 2015, and is prescribed in combination with other drugs
for the treatment of bipolar disorder, schizophrenia, and major
depressive disorder.
From a pharmacological point of view, quetiapine has a
strong affinity for serotonin 5-HT2 receptors and dopamine D2
From the *Poison Control Centre, †Representative of Clinical Research and In-
novation, and ‡Department of Addictions and Psychiatry, Angers University
Hospital, Angers; and §Pharmacology and Toxicology Department, Nantes
University Hospital, Nantes, France.
Received November 19, 2018; accepted after revision April 16, 2019.
Reprints: David Boels, PharmD, PhD, Service de pharmacotoxicologie 9,
quai Moncousu, 44093 Nantes Cedex 1, France (e-mal:
David.boels@chu-nantes.fr).
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0271-0749
DOI: 10.1097/JCP.0000000000001053
312 www.psychopharmacology.com Journal of Clinical Psychopharmacology • Volume 39, Number 4, July/August 2019
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
receptors. The antipsychotic properties of quetiapine are ex-
plained by blocking D2 receptors, whereas the reduction of extra-
pyramidal effects is explained by antagonizing 5-HT2,1 as well as
histaminergic H1 and α-adrenergic receptors.2,3
The most common symptoms of quetiapine poisoning in-
clude drowsiness, tachycardia, and respiratory depression. While
deaths have been reported,4 there have also been reports of pa-
tients surviving very high doses.5,6
Because of its recent commercialization, there are few data
on the consequences of acute ingestion of quetiapine. With regard
to acute poisoning, patients usually ingest several units, including
those that constitute their treatment.7 For several years, there has
been an increase in the number of prescriptions6,8 and also in calls
to the Angers Poison Control Centre (PCC). Furthermore, in
VigiBase (the World Health Organization's international database
of suspected adverse drug reactions), 1643 suicide attempts with
quetiapine were reported, making it the fourth most common sub-
stance used for this purpose. The purpose of this study was to de-
scribe cases of poisonings and to determine if factors can
influence the severity of cases of acute exposure to quetiapine.
Quetiapine has often been prescribed alongside other substances
(benzodiazepines, psychotropic drugs), and we studied the influ-
ence of these coagents on the clinical severity of patients' symptoms.
EXPERIMENTAL PROCEDURES
Design
A retrospective case review study listed all the calls received
by the western France PCC at Angers University Hospital between
2007 and 2017 that were related to self-poisoning with quetiapine.
Sample and Participants
The western France PCC usually receives notifications re-
garding many instances of poisoning that occur in 4 French re-
gions, representing a population of more than 12 million people.
A total of 59,000 calls are received each year, and the proportion
of calls from physicians equals 56% (compared with 39% from
the general public and 5% from nurses and paramedics).
This study was based on data collected by the Angers PCC in
telephone responses to instances of exposure to toxic substances
and during patient follow-ups, supplemented by reports from clin-
ical staff in hospitals. A case was defined as any instance of expo-
sure to quetiapine with or without symptoms.
Data were extracted from the PCC database as authorized by
the French Data Protection Authority (Commission Nationale
Informatique et Libertés, accreditation no. 747735). The personal
data of patients were anonymized before their medical records
were studied. This study fulfilled the regulation of the Hospital.
Approval of the local Ethics Committee was not necessary, given
the retrospective and noninterventional nature of this study.
A data collection form was completed by 1 clinical toxicolo-
gist and reviewed by another clinical toxicologist.
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FIGURE 1. The number of calls involving quetiapine (n = 372)—western France PCC from 2011 to October 2017.
Measures
For each selected case, all clinical variables were systemati-
cally recorded and included the following:
1. The demographic characteristics of the patient: age, sex,
and background.
2. The circumstances surrounding the poisoning event: date and
time of ingestion and estimated ingested dose (EID) (doses that
the patients admitted to having ingested or the number of tab-
lets taken as deduced from the empty blisters found near them).
3. The clinical aspects of the poisoning: clinical symptoms (neu-
rological and psychiatric symptoms, respiratory and cardiovas-
cular dysfunctions), severity of poisoning, and clinical outcome
(recovery, death).
4. The interventional procedures: admission to the intensive care
unit and the need for mechanical ventilation.
The severity of poisoning was graded using a standardized
scheme known as the Poison Severity Score (PSS) as follows9:
null (grade 0), mild (grade 1), moderate (grade 2), and severe
and fatal (grade 3) poisoning. The PSS considers the most severe
clinical symptoms (eg, cardiovascular, neurological, metabolic,
respiratory symptoms) after follow-ups. It enables a qualitative
evaluation of the lethal cases and facilitates the comparison of data.
Statistical Analysis
Continuous data were summarized by mean ± SD or median
and interquartile range and compared using Mann-Whitney U
tests. Categorical data were summarized using numbers and per-
centages and compared using exact Fisher tests.
The factors influencing the severity of poisoning were stud-
ied through a multivariate logistic regression model. The possible
explanatory factors were a priori selected based on clinical knowl-
edge. The considered factors were age (≥40 years), sex, psychiat-
ric disorders, alcohol use disorders, alcohol consumption,
benzodiazepine consumption, thymoregulators consumption,
and antidepressants consumption.
All the tests were 2-sided with a type I error set at 5%.
© 2019 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Quetiapine Poisoning and Severity
RESULTS
The first call concerning quetiapine was in 2007, before
quetiapine has been marketed in France (2010), and involved poi-
soning in a foreign patient. The second case was in 2011 (Fig. 1).
From November 2007 to October 2017, 372 cases of self-
poisoning with quetiapine were identified. Among these cases,
242 involved women and 130 involved men. The average age
was 39 years.
Circumstances were known in 367 of 372 cases; 20.2% (74
cases) of cases involved accidental exposure, with therapeutic
misadventure being the most common cause (11.7% [43 cases]).
A large majority of cases included suicide attempts (79.8%
[293 cases]).
The medical history was known in 351 of 372 cases. Three
hundred eleven patients had mental health issues (88.4%), and
61 had alcohol and/or substance use disorders (17.4%) (Table 1).
These cases were divided according to their severity: 75 cases
of null severity (grade 0), 133 cases of mild severity (grade 1), 85
cases of moderate severity (grade 2), and 79 cases of high severity
(grade 3). We listed 5 deaths in this series.
In France, quetiapine is available only in XR form. In our se-
ries, the dosage was known for 301 of 372 cases: 50 mg XR (77
cases), 300 mg XR (141 cases), and 400 mg XR (83 cases).
Neurological and cardiovascular symptoms were often
observed (Table 2).
The most frequently observed neurological symptoms in-
cluded drowsiness (89/372), coma (162/372) with Glasgow coma
scale (GCS) score of less than 8 (63/372). The most commonly
observed cardiovascular included tachycardia (108/372), hypo-
tension (46/372), and long QT syndrome (41/372). Other com-
plications were also noted: severe coma, respiratory depression
(5/372), rhabdomyolysis (20/372), and aspiration pneumo-
nia (26/372).
In this series, the concentration of quetiapine in the blood
was tested in 28 cases (0.03–7.3 mg/L). Of these 28 samples, 16
showed supratherapeutic concentrations (>1 mg/L10), and 12
showed toxic doses (>1.8 mg/L10). Of these 12 cases, there were
1 PSS 1, 10 PSS 3, and 1 PSS 4 (death).
Concerning the cases of self-poisoning, 293 of 372 poison-
ings were voluntary, which makes 79.8%. Of these cases, 69.6%
were women (204), and 91.4% (256) of these patients had a
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 Peridy et al Journal of Clinical Psychopharmacology • Volume 39, Number 4, July/August 2019

TABLE 1. Characteristics of the Population Who Suffered From Quetiapine Poisoning (n = 372)—Western France PCC From 2007 to
October 2017

Total No. Cases No. Cases %

Sex 372 Male 130 34.90
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Female 242 65.10

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Age, y 372 Average 39.2 SD, 16,6

Median 39 Q1–Q3: 27–50
Medical history 351 Yes 311 88.4
Psychiatric No 41 11.6
Alcohol/substance addiction Yes 61 17.4
No 290 82.6
Quetiapine form 301 XR 50 mg 77 25.6
XR 300 mg 141 46.8
XR 400 mg 83 27.6
Circumstances 367 Self-poisoning 293 79.8
Accidental 74 20.2
Therapeutic accident 10 2.7
Therapeutic error 43 11.7
Lack of perception 6 1.6
Misuse 15 4.1
Severity 372 Null 75 20.2
Minor 133 35.8
Moderate 85 22.8
High 79 21.2
Evolution 354 Recovery 349 98.6
Death 5 1.4

TABLE 2. Clinical and Paraclinical Signs of Self-Poisonings With Quetiapine (n = 372)—Western France PCC From 2007 to October 2017

Clinical or Paraclinical Signs* Total PSS 1 (n = 133) PSS 2 (n = 85) PSS 3 (n = 79)
Neurological
Drowsiness 89 57 (43%) 23 (27%) 9 (11%)
GCS score 14–12 60 37 (28%) 20 (23.5%) 3 (4%)
GCS score 11–8 39 36 (42%) 3 (4%)
GCS score <8 63 63 (80%)
Confusion 18 2 (1.5%) 13 (15%) 3 (4%)
Convulsion 14 3 (2%) 3 (3.5%) 8 (10%)
Psychiatric
Anxiety 25 4 (3%) 16 (19%) 5 (6%)
Hallucinations 9 8 (9%) 1 (1%)
Cardiovascular
Tachycardia 108 46 (35%) 40 (47%) 22 (28%)
Cardiac arrest 3 3 (4%)
Hypotension 46 7 (5%) 11 (13%) 28 (35%)
Cardiovascular shock 6 6 (7.5%)
Long QT 41 22 (26%) 19 (22%)
Respiratory
Aspiration pneumonia 26 3 (3.5%) 23 (29%)
Other
Rhabdomyolysis 20 7 (8%) 13 (16%)
*PSS 0 (n = 75): no adverse reaction observed.

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 Journal of Clinical Psychopharmacology • Volume 39, Number 4, July/August 2019
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FIGURE 2. Coingestion of other drugs for all cases of self-poisoning with quetiapine (n = 293)—western France PCC from 2007 to October 2017.
history of mental illness. Seventy-five of the 79 high severity cases
were linked to a suicide attempt, which was the case in 3 of the 5
deaths. The average EID was 4700 mg (minimum 50 mg to maxi-
mum 36,000 mg; median, 2400 mg), with 65.6% of the cases hav-
ing an EID greater than 1500 mg.
It was observed that, on average of the 2.8 units of quetiapine,
other substances were coingested in cases of voluntary poisoning.
Among these coagents, the most common were benzodiaze-
pines (56.3%), other antipsychotic agents (39.2%), and antide-
pressants (36.9%) (Fig. 2).
Then, we decided to study the influence of the form of quetiapine,
the evaluated ingested dose, and the link between the number of coagents
and the severity of the poisoning. Results are shown in Table 3.
In this study, among cases of voluntary consumption,
quetiapine intake was associated with at least 2 coagents, and an
EID greater than 1500 mg was strongly linked to an increase in se-
verity of the symptoms. There is no significant link between the
severity of symptoms and the form of quetiapine (dosage).
Multivariate logistic regressions were calculated for the
severity of self-poisoning and are shown in Table 4. Concomi-
tant administration of benzodiazepines and antidepressants
with quetiapine increases the risk of high severity symptoms
(odds ratio, 2.478 [confidence interval, 1.3–4.723]; odds ratio,
1.820 [confidence interval, 1.010–3.316]).
DISCUSSION
The objective of the study is to describe the quetiapine poi-
soning observed and to determine if risk factors can influence
the severity of these cases during voluntary exposure.
TABLE 3. Characteristics of Quetiapine Self-Poisoning According to Severity (n = 293)
No. Cases Severity Null, Mild, or Moderate
Quetiapine form 236 XR 50 mg 54
XR 300 or 400 mg 124
EID 215 <1500 mg 71
≥1500 mg 96
Coagents 293 0 or 1 89
≥2 129
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Quetiapine Poisoning and Severity
Quetiapine is a relatively new substance. This generation
causes fewer adverse effects, including extrapyramidal adverse ef-
fects.2,11 They are increasingly prescribed to patients.6,8,12 In
France, this increase has also been noted.13 The HAS recom-
mends using quetiapine for several conditions (bipolar disorder,
schizophrenia, and major depression in combination with other
substances). In France, the only form marketed is the XR form
in order to limit the sedating effect. The study shows an increase
in the number of calls (2011: 0.3 cases per 1000 calls involving
medication poisoning; 2017: 7.4 cases per 1000 calls). Cases
of poisoning are increasing in the United States,2 as in
France (Table 1).
The first studies concerning quetiapine qualified it as
quite harmless.14–16 However, we are now beginning to become
more cautious.17 In instances of poisoning, the symptoms
found corresponded to an exaggeration of the pharmacological
effects.2,18 Although quetiapine is more likely to cause severe
symptoms than other antipsychotics,3,4,19 it seems to be better
tolerated by patients and just as effective.1,11
There is currently no specific treatment for quetiapine poison-
ing. Care is therefore based on symptomatic treatment and monitor-
ing patients (particularly on a neurological and cardiological level).
In our study, the most commonly found symptoms included
central nervous system (CNS) depression (drowsiness, coma) and
tachycardia, as seen in many cases.2,4,6,7,20–22 Quetiapine poison-
ing can cause serious medical issues: of the 79 PSS 3, 80% had a
GCS score of less than 8, 6 went into cardiovascular shock, and
there were 3 cardiac arrests (Table 2). The depressant effects on
the CNS could be explained by the quetiapine H1 receptor's antag-
onist properties.2,4,23 Quetiapine in XR is generally better
High Severity P
30.3% 10 17.2% 0.061
69.7% 48 82.8%
42.5% 3 6.3% <10E−4
57.5% 45 93.8%
40.8% 11 14.7% <10E−4
59.2% 64 85.3%
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 Peridy et al Journal of Clinical Psychopharmacology • Volume 39, Number 4, July/August 2019
TABLE 4. The Severity of Poisoning for All Cases of Self-Poisoning With Quetiapine (n = 293) - Western France PCC From 2007 to
October 2017 (5.6% of Missing Values)
Odds Ratio
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Age (reference: <40 y) 1.203
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Sex (reference: female) 1.106
Substance use disorders (reference: no) 0.857
Psychiatric disorders (reference: no) 1.293
Benzodiazepines (reference: no) 2.478
Antimanic drugs (reference: no) 0.829
Alcohol (reference: no) 0.938
Antidepressants (reference: no) 1.820
CI indicates confidence interval.
tolerated than in IR form. In addition, it causes less drowsiness
than in IR form in the first hours, especially when treatment has
just started.24–26 It could nevertheless be supposed that in the
event of poisoning the effects on the CNS would last a long time
because of the extended release. Thus, there is a risk of
extended coma, with consequences such as rhabdomyolysis and
aspiration pneumonia.
In terms of cardiotoxicity, the first symptom observed was
tachycardia, followed by hypotension and QT prolongations
(without torsade de pointes).2,6,15,17,21 Cardiotoxicity, including
tachycardia, is explained by the affinity of quetiapine for α-
adrenergic receptors.15,21
In our series, we noted a correlation between an EID of
1500 mg or greater (ie, a box of XR 50 mg) and high severity of
symptoms. This means that from 1 ingested box the risk to the pa-
tient is already high, and they would require hospitalization in in-
tensive care; 93.75% (45/48) of high severity cases had an EID of
1500 mg or greater. On the one hand, we can suppose that the
higher the dose, the higher the severity, unlike Hunfeld et al,7
who do not observe any relationship here. On the other hand, we
found neither a link between the EID and the form of quetiapine
(50 mg vs 300 or 400 mg) nor a correlation between the dosage
and the severity of the cases. In other words, the study did not
show a relation between the prescribed form and the severity of
symptoms. The concentration of quetiapine in the blood is not
usually measured in toxicology, although it has therapeutic impli-
cations. In our series, a few tests were performed. However, we do
not have enough data to assess whether serum concentration cor-
relates with severity. The dosage is of diagnostic and postmortem
interest (to determine the cause of death).27 An overdose of
quetiapine causes death,4,28 as a result of interactions between
coingested agents.17,28
In our study, we noted a correlation between voluntary poi-
soning with at least 2 coagents and degrees of severity. Moreover,
deaths due to the coingestion of other substances were observed
(from 2 to 6 molecules) in our study.14 We observed a significant
correlation between severity, benzodiazepine, and related intake.
Benzodiazepines are often coprescribed to psychiatric patients, par-
ticularly for their anxiolytic and sedative properties. They were also
found to be present in several other studies on quetiapine.7,13,29 The
risk of poisoning increases for a patient taking quetiapine and
benzodiazepine. Indeed, CNS depression is increased because
quetiapine's effect on the CNS increases with the action of ben-
zodiazepines. In some cases, CNS depression is also increased
by an interaction with cytochromes.7 Similarly, in several other
cases, quetiapine is combined with other antidepressants. In our
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95% CI
Lower Upper P
0.676 2.142 0.530
0.594 2.058 0.751
0.398 1.848 0.695
0.404 4.135 0.665
1.300 4.723 0.006
0.280 2.454 0.735
0.422 2.082 0.874
1.010 3.316 0.050
study, antidepressants were associated with severe poisoning. It
is important to question the danger in combining these substances.
Reluctantly, the HAS has already issued an opinion on the use of
quetiapine as an adjunctive therapy for major depressive episodes.
The results of this study contribute to the argument of the rele-
vance of this use of quetiapine.
As described in the literature, the majority of poisonings in
our sample were voluntary, that is, 79.8% of cases.4,7,13,21 A his-
tory of mental health issues and a history of alcohol dependency
were identified as risk factors for suicide attempts.30,31
In our series, 82% of patients had a history of mental health
issues. This rate rises to 91% in cases of intentional poisoning.
This is partly because quetiapine is prescribed for psychiatric dis-
orders.7,18,32 However, we can warn people about the type of psy-
chiatric care these patients are receiving.
Quetiapine is prescribed in different dosages and different
situations. In schizophrenia, quetiapine will be prescribed between
400 and 800 mg, whereas in bipolar disorder, the prescription
will not exceed 600 mg to prevent a thymic episode and mostly
around 300 mg in case of depressive episode. The great interest
of this treatment is that, like an antipsychotic, it has an action
against delusion and moreover an antidepressive effect, unlike
other antipsychotic drugs. In our study, the risk increased when
quetiapine was associated with other psychotropic drugs, in par-
ticular benzodiazepines and antidepressants. The coprescription
is very usual in psychiatric disorders, and it should be interest-
ing to evaluate the pertinence of each prescription, including
blood concentration to optimize the positive effect of each treat-
ment rather than adding new treatment. Most of the acute poison-
ing was in a suicidal condition. This is particularly important to
adjust the prescription and the monitoring of suicidal ideas.33 In
France, the delivery of treatment is monthly. So, the more different
kind of treatment is prescribed, the more pills are available
at home.
Quetiapine overdose may lead to severe poisoning. Physi-
cians should be particularly attentive as there is no specific treat-
ment for this. It is important to monitor the symptoms, particularly
with atypical antipsychotics, even though they are considered
safer than the first generation.21 Estimated ingested dose and
coagents can serve as predictors of severity, particularly when
benzodiazepines, antidepressants, and other psychotropic drugs
are present. It is therefore important that care staffs are aware of
coprescribed/coingested substances.
Because of the particular profile of the patients on
quetiapine, it seems important to be vigilant with regard to the
dosages administered and the therapeutic schemes proposed to
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 Journal of Clinical Psychopharmacology • Volume 39, Number 4, July/August 2019
the patients. The recommendations err on the side of caution, es-
pecially when used in cases of major depression, associated with
other therapies.
AUTHOR DISCLOSURE INFORMATION
The authors declare no conflicts of interest.
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