Original article
Emerg Med J: first published as 10.1136/emj.2009.076596 on 5 October 2010. Downloaded from http://emj.bmj.com/ on August 2, 2023 at Universidad Austral De Chile Bibliteca Central.
< An additional supplementary
figure is published online only.
To view this file please visit the
journal online (http://emj.bmj.
com).
Department of Emergency
Medicine, Dicle University,
Faculty of Medicine, Diyarbakır,
Turkey
Correspondence to
Dr Cahfer Güloglu, Dicle
University, Faculty of Medicine,
Department of Emergency
Medicine, 21280 Diyarbakır,
Turkey; cahgul@hotmail.com
Accepted 20 March 2010
Published Online First
5 October 2010
296
Analysis of amitriptyline overdose in
emergency medicine
Cahfer Güloglu, Murat Orak, Mehmet Üstündag, Yusuf Ali Altuncı
ABSTRACT
Introduction Amitriptyline is a tricyclic antidepressant. In
general, toxicity effects develop within 30 min of
overdose and peak from 2 h to 6 h. Anticholinergic
effects predominate in cases of low dose ingestion. In
cases of high dose ingestion, marked depression of the
central nervous system is coupled with cardiotoxicity,
seizures and hypotension.
Patients and methods Amitriptyline-intoxicated
patients admitted to the emergency department (ED) of
Dicle University Hospital were evaluated between
January 2005 and April 2007. Social and demographic
status, clinical and laboratory findings, treatments and
outcomes were recorded. Age, sex, marital status, time
of hospital admission, consciousness levels, ECG
findings, requirement for respiratory support, follow-up
periods and antidepressant overdose risk assessment
(ADORA) criteria were analysed using SPSS software.
Results A total of 110 cases of overdose by
amitriptyline was evaluated. Suicide attempts by
amitriptyline overdose in adult single women were the
commonest finding. The commonest symptoms seen
during initial examinations were sinus tachycardia
(66.3%), altered mental state (78.1%) and hypotension
(7.3%). Mechanical ventilatory support was required in
9.1% of cases. Most patients (n¼76, 69.1%) were
treated in the ED (p¼0.001). 60 (54.5%) patients were
discharged from the ED within 24 h after admission
(p<0.0001).
Conclusion Most of the patients were young single
women. Altered mental state and tachycardia were the
commonest symptoms. The initial symptoms of
amytriptyline overdose patients may be life threatening,
but effective supportive treatments were helpful. There
was high correlation between ADORA criteria and the
dose ingested.
Imipramine, amitriptyline, their /V-demethyl
derivatives and other similar compounds were the
first successful antidepressants and, since the early
1960s, have been widely used for the treatment of
major depression.1 These agents block the reuptake
of synaptic transmitters such as norepinephrine,
dopamine and serotonin in the central nervous
system (CNS). Tricyclics are well absorbed from
the gastrointestinal tract. Tricyclics exhibit high
protein binding in the plasma.2 3 Elimination is
mainly by hepatic metabolism. The half-lives of
tricyclics and their metabolites range from 25 to
30 h but may be longer in the overdose setting.3
Clinical toxicity effects generally develop within
30 min of overdose and peak in 2e6 h. In cases of
low overdose, anticholinergic effects predominate.4
Any dose greater than 5 mg/kg per day has the
potential to produce tricyclic antidepressant (TCA)
toxicity. Life-threatening symptoms usually occur
with ingestions of more than 10 mg/kg in adults.2
In cases of high overdose, marked CNS depression
is coupled with cardiotoxicity, seizures and hypo-
tension. Ventricular tachyarrhythmia, atrioventric-
ular and intraventricular conduction delays,
terminal bradycardia and decreased cardiac output
may occur. Increasing duration of the QRS complex
correlates with an increased risk of cardiac
arrhythmias and seizures. In the evaluation of
clinical findings for poisoning by antidepressant
medications, the antidepressant overdose risk
assessment (ADORA) criteria are used. These criteria
are: prolongation of the QRS interval; arrhythmias;
altered mental status; seizure; respiratory depression
and hypotension.4
In this study we evaluated Dicle University
emergency department (ED) patients with amitrip-
tyline overdose by their social demographic, clinical
and laboratory findings and outcomes. We aimed to
Protected by copyright.
utilise the ADORA criteria for clinical findings of
patients’ pure amitriptyline overdoses.
MATERIALS AND METHODS
In this study, all patients over 15 years of age who
were admitted to Dicle University Hospital ED for
amitriptyline overdose ingestion from January 2005
to March 2007 were enrolled. Age, gender, martial
status, admitted time, ingested dose, initial symp-
toms, physical examination, ECG and arterial blood
gas findings, the need for endotracheal intubation
and/or mechanical ventilatory support, follow-up
period, ADORA criteria, performed treatment
attempts (gastric emptying, activated charcoal,
etc), hospitalisation and discharging features were
recorded and analysed statistically.
Table 1 lists the ADORA criteria. Patients with
one or more of the criteria were classified as high
risk (HR). Patients not displaying any of these
criteria within 6 h from ED application of ADORA
were classified as low risk (LR).4
We evaluated our pure amitriptyline overdose
patients with ADORA criteria for the first 6 h from
ED admission and did not repeat this evaluation.
The toxic dose for amitriptyline is over 10 mg/kg.
Most of our cases were young women and, because
of our region’s anthropological features, we
accepted 50 kg as the overdose quantity. We could
not detect blood amitriptyline levels due to the
limitations of our laboratory, so we compared
ADORA criteria with pure amitriptyline overdose
patients.
Statistical analyses were performed using the
Student’s t test for comparing mean of groups and
the c2 test for non-parametric data. Statistical
significance was set at the 5% level.
Emerg Med J 2011;28:296e299. doi:10.1136/emj.2009.076596
 Original article

Table 1 Results of ADORA criteria in the cases with
amitriptyline overdose
ADORA criteria N %
Arrhythmias 73*
Altered mental status 86
Conduction block 4 3.6
Hypotension 8 7.3
Respiratory depression 10
Seizures 1 0.9
*One paroxysmal supraventricular tachycardia, three ventricular
premature complex, one left bundle branch block and 68 sinusal
tachycardia.
ADORA, antidepressant overdose risk assessment.
RESULTS
During to our study 129 amitriptyline overdose patients were
admitted to our emergency service. We excluded 19 patients
because of the co-ingestion of different drugs. The social
demographic features of our 110 amitriptyline overdose patients
are shown in table 2. For our retrospective study the number of
women (n¼99, 90%) was scientifically more than men (n¼11,
10%; p<0.0001). The average age for the women was
(22.768.3 years) and for the men (24.066.9 years; p>0.05).
Cases were admitted to our hospital 2.1861.44 h after ingestion.
Single cases (n¼78, 71%) were statistically more than married
patients (n¼32, 29%; p<0.0001). Most of the overdose events
happened at home (n¼107, 97.3%); the remainder (n¼3, 2.7%)
Emerg Med J: first published as 10.1136/emj.2009.076596 on 5 October 2010. Downloaded from http://emj.bmj.com/ on August 2, 2023 at Universidad Austral De Chile Bibliteca Central.
(n¼14, 12.7%). The initial symptoms for our overdose patients
by order of their frequency were altered mental status (n¼86,
78.1%) and tachycardia (n¼73, 66.3%; p<0.0001).
66.3
Hypoxia was seen (n¼25, 22.7%) in 110 patients in the arte-
78.1 rial blood gases. We intubated 10 (9.1%) of them and initiated
mechanical ventilatory support.
Most of our patients (n¼76, 69.1%) were treated in our ED
9.1 and the rest of them (n¼34, 30.9%) were followed in the
intensive care unit (ICU). We discharged 60 (54.5%) patients
from our ED 24 h after admission (p<0.0001). Gastric lavage
alone was performed in one (0.9%) patient, active charcoal alone
was administered to eight (7.3%) patients and 76 (69%) of the
total number of cases received both treatments. We applied
combined therapy to high ingested dose patients whose ADORA
criteria were positive (10 cases needed ventilatory support).
Amitriptyline overdoses were seen every month, and the
distribution of cases shows a particular regulation month by
month. Nevertheless, amitriptyline overdose patients were still
decreasing (see supplementary figure 1, available online only).
For our 14 (12.7%) of 110 patients’ initial examination, we
could not find any clinical features of overdose. In contrast, 96
(87.3%) patients had major overdose symptoms that were
related to ADORA criteria. The most common initial features of
toxicity were altered mental status (n¼86, 78.1%) and
arrhythmias (n¼73, 66.3%; p<0.001) (table 1).
There were no statistical differences between the groups with
regard to gender, mechanical ventilatory support and hospital-

Protected by copyright.
isation period (p>0.05). We found a significant difference in
occurred elsewhere. Most of the ingestions (n¼109, 99.1%) were
marital status and treatment unit between the two groups
suicide attempts.
(p<0.05). Fifty-five patients ingested over 500 mg amitriptyline,
We classified overdose patients into two groups based on their
53 of them were in the HR group. The relationship between the
ADORA score: the HR group (n¼96, 87.3%) and the LR group
ingestion of over 500 mg and high ADORA criteria was statis-
tically significant in this study (p¼0.004). The mean average
amount of amitriptyline ingested by the HR group was higher
Table 2 Characteristics of the cases with amitriptyline overdose than the LR group (HR 520.316278.6, LR 301.796128.4;
Characteristics n % p Value p<0.001; table 3). None of the patients died.
Sex
Female 99 90 <0.001 Table 3 The relationship between HR and LR according to the ADORA
Male 11 10 criteria
Age (years) Groups
Female (mean6SD) 22.768.3 >0.05 Parameters LR (n[14) HR (n[96) p Value
Male (mean6SD) 24.066.9
Sex
Admission time (mean6SD) 2.1861.44 e
Female 13 86 0.577
Martial status
Male 1 10
Single 78 71 <0.001
Marital status
Married 32 29
Single 6 72 0.018
ADORA
Married 8 24
Low risk 14 12.7 <0.001
Age (year; mean6SD) 27.71611.4 22.1367.4 0.033
High risk 96 87.3
Followed up
Symptoms
In ED 13 63 0.032
Altered mental status 86 78.2 <0.001
In ICU 1 33
Hypotension 8 7.3
Hospitalisation period
Tachycardia 73 66.4
<24 h 11 48 0.520
Seizures 1 0.9
24e72 h 3 37
Arterial blood pressure
>72 h 0 11
Hypoxia 25 22.7 e
Hypoxia 3* 22 0.603
Followed up
Mechanical ventilatory support 0 10 0.356
In ED 76 69.1 0.001
Amitriptyline ingested dose
In ICU 34 30.9
#500 mg 12 43 0.004
Hospitalisation period
>500 mg 2 53
<24 h 60 54.5 <0.001
Amitriptyline ingested dose (mean6SD) 301.796128.4 520.316278.6 <0.001
24e72 h 38 34.5
>72 h 12 11 *Three of 14 patients with hypoxia in the LR group were developed based on aspiration and
were followed up for one of them in the ICU.
ADORA, antidepressant overdose risk assessment; ED, emergency department; ICU, ADORA, antidepressant overdose risk assessment; ED, emergency department; HR, high
intensive care unit. risk; ICU, intensive care unit; LR, low risk.

Emerg Med J 2011;28:296e299. doi:10.1136/emj.2009.076596 297

 Original article
DISCUSSION
TCA is the most common agent for antidepressant overdoses.5 6
TCA feature many characteristic signs and symptoms when
present at toxic levels, but asymptomatic patients may deteri-
orate rapidly; history and physical examination alone are
insufficient to predict severe poisoning.7 In the USA, TCA
account for the third largest number of deaths, and amitriptyline
is the most common single causative agent.8
Amitriptyline is one of the most commonly prescribed and
sold antidepressant agents; also it is the agent most commonly
involved in suicide or possible suicide caused by antidepressants
in many countries.9 Deaths related to amitriptyline are often
ascribed to suicidal tendencies, and the high rate of mortality is
due to CNS and cardiovascular toxicities.10
Young female patients constitute a large part of intoxications
according to case reports in the literature.6 11 Harrigan et al7
reported a case series with three patients who were all women
and were aged 18, 24 and 31 years. Two of them presented
within 2 h of intoxication and the other within 6 h. In a study
of Unverir et al12 TCA were the most frequently ingested anti-
depressants (58.4%). Opipramol and amitriptyline accounted for
the majority of TCA (31.2%, n¼111 and 23.3%, n¼83, respec-
tively). In their study, 78% of cases were women and the mean
age was 28610 years for all patients. The mean time of admis-
sion to the ED after ingestion was 3.3964.9 h (0.1e48). In our
study, most of the cases were women (90%), the mean age for
female patients was 22.567.9 years and 23.268.1 years for male
patients. There was no significant difference between female and
male patients’ ages. Generally, patients presented to our ED
within 2.1861.44 h after ingestion. Single patients (71%)
constituted a large part of the intoxicated cases as a result of our
religion’s social structure, we think. Young women are forced
into arranged marriages by their families and domestic violence
still happens to women in our religion. For married patients
economic problems are the main reason for taking an overdose.
In a study by Unverir et al12 a total of 97.5% of patients’
ingested drugs for suicide and the rest of them ingested for
sleeping, relaxing, accidentally etc. Substantially all of our
overdose patients were suicide attempts.
The abnormal findings in amitriptyline overdosage include
anticholinergic symptoms (pupil dilatation, tachycardia, urinary
retention, etc.), cardiac complications (a prolonged QTc interval
or QRS duration, sinus tachycardia), respiratory depression/
insufficiency, hypotension, impaired consciousness (from leth-
argy to coma), convulsions and rarely adult respiratory distress
syndrome.13 In a study by Koppel et al,14 the most frequent
symptoms in both groups were impaired consciousness, anti-
cholinergic symptoms, seizures, arrhythmia and hypotension.
Respiratory insufficiency necessitated respiratory therapy in 63
of the patients.14 Zhu et al15 reported 20 adult cases of
amitriptyline poisoning. The main symptoms were coma in
different degrees, pupil dilatation, tachycardia and urinary
retention. Hypertension, hypothermia and convulsive attacks
appeared in some of the patients. ECG was abnormal in half of
the patients.
TCA overdosage can cause life-threatening cardiac effects,16
but sinus tachycardia is the most commonly seen symptom in
patients.2 Seizures determine the seriousness of intoxication,
although a number of studies found a seizure rate of between 4%
and 24%.6 17 The most commonly seen symptoms were altered
mental status (78.2%) and tachycardia (66.4%) in our initial
examination. Hypotension and seizures were the other symp-
toms. ECG was administered to all patients, 66.3% of them were
298
Emerg Med J: first published as 10.1136/emj.2009.076596 on 5 October 2010. Downloaded from http://emj.bmj.com/ on August 2, 2023 at Universidad Austral De Chile Bibliteca Central.
abnormal. The seizure rate was low (n¼1, 0.9%). Most of our
amitriptyline patients were in the HR group (87.3%).
Intubation depends on the patient’s symptoms, Glasgow
Coma scale and laboratory findings. Intubation is mostly
reported in TCA intoxications (23e68%).18 Unverir et al12
reported a total 9.6% intubation rate, but 23 of their 24
amitriptyline overdosage cases required intubation (95.8%). In
our study, 22.7% of cases had hypoxic arterial blood gas results
and 9.1% of cases were intubated for mechanical ventilatory
support. All of the intubated patients were in the HR group, had
altered mental status and had ingested for suicide.
TCA intoxicated patients require ICU more than other
depressant overdosages.5 Similarly, the follow-up period is longer
than other depressant overdosage. A study reported 14 h for this
period.6 Unverir et al12 reported a mean observation time in the
ED for 356 patients admitted to hospital because of antidepres-
sant poisoning of 6.066.8 h (range 0.5e72). The percentage of
patients who were observed for less than 8 h was 62.1% (n¼221).
Patients who were poisoned by TCA were observed in the ED
significantly longer than those poisoned by selective serotonin
re-uptake inhibitor agents (8.54 and 6.51 h). We observed 69.1%
of cases in the ED and 30.9% required ICU observation. In total,
54.5% of patients were discharged from the ED within 24 h after
admission. Although amitriptyline overdose patients’ initial
symptoms seems to be life threatening, effective supportive
treatments (eg, respiratory) dramatically decreased mortality.
In amitriptyline poisoning, therapy includes primary detoxifi-
Protected by copyright.
cation by gastric lavage and repeated administration of activated
charcoal.13 In a TCA intoxication study, Philips et al5 applied
gastric lavage to 70% of patients and gave activated charcoal to
96% of their patients. Bosch et al19 have also stated that gastric
lavage was performed in 71% of patients with antidepressant
poisoning, 93% were given activated charcoal and 21% were
administered sodium bicarbonate. Unverir et al12 reported that
gastric lavage alone was performed and activated charcoal alone
was administered in 3.9% (n¼14) and 17.1% (n¼61) of patients,
respectively; combined gastric lavage and activated charcoal was
performed in 63.8% (n¼227) of patients. In the present study,
gastric lavage alone was performed in one (0.9%) patient, active
charcoal alone was administered to eight (7.3%) patients and 76
(69%) of the total number of cases received both treatments.
High ingested dose patients who had ADORA criteria were
treated aggressively (eg, mechanical ventilatory support was
applied to 10 patients). Similarly, the combined therapy rate is
high for our report because, despite prehospital lavage and char-
coal administration, lower intestinal motility suggested poor
elimination of TCA, so we repeated the combined therapy.
Previous studies have reported June and July to be the months
in which the most instances of intoxication are seen.11 20 Vari-
ously, Unverir et al12 suggested that the ingestion of anti-
depressants was most frequent in July and October (11% and
10.7%, respectively). June was the month with the most
hospitalisations in the present study. We reported that
amitriptyline overdoses could be seen in every month; however,
amitriptyline overdose patients were still decreasing.
Previously, it was determined that 70.9% of the remaining 306
patients (n¼217) had major poisoning clinical findings related to
the ADORA criteria. The most commonly seen symptoms were
arrhythmias (41.3%) and altered mental status (35.7%).12 Foulke
et al4 suggested cardiac arrhythmias or conduction defects as an
ADORA criterion (systolic blood pressure (<90 mm Hg), supra-
ventricular or ventricular arrhythmias, seizures and respiratory
failure). We evaluated sinus tachycardia as a supraventricular
Emerg Med J 2011;28:296e299. doi:10.1136/emj.2009.076596

arrhythmia in the same way that Unverir et al12 suggested sinus 2.
tachycardia as a cardiac arrhythmia. They confirmed a range as
41.8% for sinus tachycardia. Caravati et al21 detected major 3.
toxicity in 65 (61%) patients of 106 TCA intoxicated patients. We
confirmed major clinical findings for intoxication, which were
4.
germane to ADORA criteria in 87.3% of cases. The most
frequently reported symptoms were altered mental status and 5.
arrhythmias.
In the evaluation of clinical findings for poisoning by anti- 6.
depressant medications, the ADORA criteria are used. Patients
with one or more of the criteria were classified as high risk. Risk
evaluation of the patients should obviously include careful 7.
assessment of the respiratory status.4 We also used the ADORA 8.
criteria to evaluate overdosage patients’ clinical findings. Our 55
patients ingested more than 500 mg amitriptyline, 53 of them
9.
were in the HR group. The relationship between ingestion
greater than 500 mg and high ADORA criteria was statistically 10.
significant for our study (p¼0.004). A high correlation between
ADORA criteria and the ingested dose showed the relationship 11.
between ADORA criteria and the dose-dependent clinical 12.
toxicity risk.
In conclusion, most of our patients were young single women.
13.
Clinical findings were evaluated by the ADORA criteria. Altered
mental status and tachycardia were the most commonly seen 14.
symptoms. Although amitriptyline overdose patients’ initial
symptoms seems to be life threatening, effective supportive 15.
treatments (eg, respiratory) dramatically decreased mortality.
We cannot detected blood levels but a high correlation 16.
between ADORA criteria and the ingested dose showed the 17.
relationship between ADORA criteria and the dose-dependent
clinical toxicity risk. 18.
Competing interests None. 19.
Provenance and peer review Not commissioned; externally peer reviewed.
20.
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