Tricyclic antidepressant poisoning

Author: Steven D Salhanick, MD

Section Editor: Robert G Hendrickson, MD, FACMT, FAACT
Deputy Editor: Michael Ganetsky, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review
process is complete.

Literature review current through: Jun 2024. | This topic last updated: Jul 19, 2024.

INTRODUCTION

Between the late 1950s and the late 1980s, tricyclic antidepressants
(TCAs) were used extensively in the management of depression and
other psychiatric disorders. Although selective serotonin reuptake
inhibitors (SSRIs) and other agents have supplanted TCAs as first line
therapy in the management of depression, TCAs are still used for
depression and other indications including migraine, pain, and
insomnia [1]. Consequently, TCA poisoning, which can be life-
threatening, remains a significant clinical issue.
The diagnosis and management of TCA poisoning is reviewed here. A
summary table to facilitate the emergent management of TCA
overdose is provided ( table 1). The management of SSRI poisoning
and a general clinical approach to the patient with known or suspected
drug poisoning are discussed separately. (See "Selective serotonin
reuptake inhibitor poisoning" and "General approach to drug poisoning
in adults" and "Initial management of the critically ill adult with an
unknown overdose".)

PHARMACOLOGY

Inhibition of presynaptic neurotransmitter reuptake (norepinephrine

and serotonin) is the primary mechanism for the therapeutic effects of
tricyclic antidepressants (TCAs).
Following overdose, the following cellular effects often produce
important clinical consequences:
● Blockade of cardiac fast sodium channels
● Antagonism of central and peripheral muscarinic acetylcholine
receptors
● Antagonism of peripheral alpha-1 adrenergic receptors
● Antagonism of histamine (H1) receptors
● Antagonism of CNS gamma-aminobutyric acid (GABA) A receptors
In therapeutic use, TCAs are rapidly absorbed from the gastrointestinal
tract, reaching maximal plasma concentrations within two to eight
hours. TCAs are lipophilic and highly bound to plasma and tissue
proteins and thus have a large volume of distribution (Vd), ranging
from 10 to 50 L/kg. The fraction of the drug found in the plasma is
usually highly bound to alpha-1 acid glycoprotein. TCAs are primarily
metabolized by the liver, undergoing phase one metabolism primarily
via CYP 2D6 and phase 2 glucuronidation. Many phase one metabolites
are pharmacologically active and may persist in the plasma for 12 to 24
hours [2-4]. Depending upon the TCA, the half-life of the parent
compound can range from 7 to 58 hours. Approximately 70 percent of
the total dose is renally excreted as inactive metabolites; the remainder
is eliminated primarily via the biliary system, with a small amount
excreted unchanged in the urine. Enterohepatic recirculation can delay
final elimination of a large fraction of the drug [5,6].
Important changes make it impossible to extrapolate overdose kinetics
from kinetics measured during therapeutic dosing. Absorption may be
delayed, largely due to decreased gut motility from anticholinergic
effects. Bioavailability may be increased as metabolic pathways become
saturated, reducing the first pass metabolism. Acidemia, which
frequently complicates overdose, may increase the amount of free drug
due to effects on plasma glycoprotein binding. Genetic polymorphisms
of CYP2D6 resulting in a decreased rate of elimination, may become
more relevant following overdose [7]. The sum total of these effects is
often delayed absorption, an increased proportion of active drug, and
delayed excretion.

CARDIOVASCULAR PATHOPHYSIOLOGY

Cardiac conduction abnormalities occur during tricyclic antidepressant

(TCA) poisoning because TCAs inhibit the fast sodium channels in the
His-Purkinje system and myocardium. This inhibition decreases
conduction velocity, increases the duration of repolarization, and
prolongs absolute refractory periods ( figure 1) [8,9]. These effects are
similar to those of the Vaughan-Williams Class IA antiarrhythmic drugs
such as quinidine. Mechanisms that contribute to hypotension during
overdose include decreased contractility from reduced calcium influx
into ventricular myocytes, blockade of rapid sodium channels, and
peripheral vasodilatation from blockade of alpha 1 adrenergic
receptors [10]. (See "Cardiac excitability, mechanisms of arrhythmia,
and action of antiarrhythmic drugs".)

CLINICAL FEATURES

History — It is important to learn the particular tricyclic antidepressant

(TCA) ingested and the amount, and whether the patient took any other
agents. In the event of mental status changes, information can be
obtained from emergency medical personnel, police, family, friends,
pharmacists, psychiatrists, and primary care clinicians. (See "General
approach to drug poisoning in adults", section on 'History'.)
Overview of physical findings — Signs of TCA poisoning typically
include sedation, but may also include confusion, delirium, or
hallucinations. Cardiac conduction delays, arrhythmias, hypotension,
and anticholinergic toxicity (eg, hyperthermia, flushing, dilated pupils)
are also common ( table 1) [3,4,11,12]. The clinical course of patients
with TCA poisoning can be unpredictable, and patients who present
immediately after ingestion may initially be well-appearing, only to
deteriorate rapidly, due to the variable absorption kinetics described
above. In most cases, acute TCA ingestions of 10 to 20 mg/kg lead to
significant cardiovascular and central nervous system (CNS) toxicity
[13]. (See 'Pharmacology' above and "General approach to drug
poisoning in adults".)
Cardiovascular toxicity — Sinus tachycardia is common in TCA
overdose, likely due to anticholinergic (vagolytic) effects and
hemodynamic decompensation causing a reflex tachycardia.
Hypotension is common following significant TCA poisoning, and
mortality from TCA overdose is due largely to refractory hypotension.
Hypotension is primarily secondary to peripheral alpha-1 adrenergic
receptor antagonism [14,15]. Cardiac conduction abnormalities may
also contribute to hypotension.
Ventricular tachycardia and ventricular fibrillation (VT and VF) occur in
approximately 4 percent of TCA overdose cases [16]. VT and VF are
more common in severe poisonings (eg, displaying severe acidosis, or
hypotension), particularly those involving extreme QRS prolongation.
CNS toxicity — Mental status changes, such as a decreased level of
consciousness (due to antihistaminic effects) or, less frequently,
delirium (due to anticholinergic effects), are common following TCA
overdose.
TCA poisoning can cause seizures, likely due to the antagonist effects of
TCAs on the GABA-A receptor [17,18]. Most seizures are brief and self-
limited, but some are associated with cardiovascular deterioration,
including hypotension and ventricular arrhythmia [19,20]. Maprotiline
has been associated with a greater frequency of seizures and
arrhythmias than other TCAs [21].
Anticholinergic toxicity — TCAs have anticholinergic effects and signs
of TCA poisoning can include hyperthermia, flushing, dilated pupils that
respond poorly to light, delirium, intestinal ileus, and urinary retention.
(See "Anticholinergic poisoning", section on 'Clinical features of
overdose'.)

DIAGNOSTIC TESTING
General approach — Laboratory studies and other diagnostic testing
are directed toward establishing the diagnosis, estimating the severity
of intoxication, and ruling out additional toxicities. (See "General
approach to drug poisoning in adults".)
Routine laboratory evaluation of the poisoned patient should include
the following:
● An electrocardiogram, to assess for cardiac conduction
abnormalities (this is particularly important in tricyclic
antidepressant [TCA] ingestions)
● Fingerstick glucose, to rule out hypoglycemia as the cause of any
alteration in mental status
● Acetaminophen and salicylate levels, to rule out these common co-
ingestants
● Pregnancy test for women of childbearing age
Electrocardiogram
Monitoring and overview of conduction abnormalities — Cardiac
conduction abnormalities are common in patients with TCA poisoning.
Therefore, obtaining an electrocardiogram (ECG) immediately upon
presentation is essential in patients with known or suspected TCA
poisoning ( table 1). Arrhythmias from a TCA overdose can develop
quickly and ECGs should be obtained frequently until the patient has
been free of any symptoms or signs of cardiac toxicity for several
hours. We suggest obtaining an ECG approximately every hour, but
more frequent studies are needed if the patient manifests signs of
cardiotoxicity or conduction abnormalities are evident on the initial ECG
or a cardiac monitor.
The following signs suggest cardiotoxicity:
● Prolongation of the QRS >100 msec
● Abnormal morphology of the QRS (eg, deep, slurred S wave in
leads I and aVL) ( waveform 1)
● Abnormal size and ratio of the R and S waves in lead aVR: R wave in
aVR >3 mm; R to S ratio in aVR >0.7
These signs are used as important tools in diagnosis, risk stratification,
and management ( waveform 2A-D). However, none is completely
reliable in the individual patient, and significant toxicity can occur
despite falsely reassuring indices [22]. Preexisting conduction delay
may also complicate interpretation. We view prolongation of the QRS
duration >100 msec as a sign of potential cardiac toxicity, and as an
indication for a trial of therapy with intravenous (IV) sodium
bicarbonate. (See 'Sodium bicarbonate for cardiac toxicity' below.)
Other possible ECG findings with TCA poisoning include prolongation of
the PR and QT intervals, block within the His-Purkinje system, and
intraventricular conduction delay (eg, bundle branch block). Because of
its relatively longer refractory period, the right bundle branch is
especially sensitive to block from TCA overdose [23]. Several reports
have described a Brugada type pattern following TCA overdose, with
the incidence ranging from 2.3 to 15 percent following overdose
[24,25]. These conduction system abnormalities may contribute to the
hypotension seen in TCA poisoning. Although QT prolongation is
common in TCA overdose, the polymorphic ventricular tachycardia
associated with QT prolongation, Torsade de Pointes (TdP), is not.
QRS duration — The most prominent electrocardiographic
manifestation of TCA toxicity is widening of the QRS interval. In one
prospective series, patients with a QRS duration less than 100 msec did
not suffer a seizure or a ventricular arrhythmia; those with a QRS
duration >100 msec had a 26 percent chance of seizure; and those with
a QRS duration >160 msec had a 50 percent chance of a ventricular
arrhythmia [26]. Although some authors have questioned the utility
and reproducibility of QRS duration analysis [22,27,28], other studies
confirm the predictive value of QRS duration for seizure and ventricular
arrhythmia [29-32]. In the setting of a TCA overdose, we consider a QRS
interval duration greater than 100 msec an indication for bicarbonate
therapy. (See 'Sodium bicarbonate for cardiac toxicity' below.)
Terminal frontal plane QRS vector — Delayed right ventricular
activation from intra and interventricular conduction delays in the
setting of TCA overdose has been shown to cause a rightward shift in
the terminal 40 milliseconds of the frontal plane QRS vector
[23,29,30,33]. Precise measurement of this parameter can be
performed but is complex and rarely done at the bedside. In qualitative
terms, this conduction delay manifests as a deep, slurred S wave in
leads I and aVL, and an R wave in lead aVR ( waveform 1 and
waveform 2A). (See "Basic approach to delayed intraventricular
conduction".)
As a result of this differential conduction delay, R wave amplitude in
lead aVR (RaVR) and the ratio of R:S wave amplitude in aVR (R/SaVR) are
significantly higher in patients with a TCA overdose compared to
matched controls [30]. One cohort study noted that the risk of seizures
and ventricular arrhythmias was increased in patients with RaVR >3
mm, R/SaVR >0.7, and QRS duration >100 msec [30].
Measurement of TCA concentrations — Qualitative (urine) and
quantitative (serum) TCA testing have limited therapeutic and
prognostic utility in the acute setting. Significant illness can occur at
drug concentrations not classically described as toxic, especially in
children and in patients taking TCAs on a chronic basis [29,34,35]. In
addition, a positive qualitative test only indicates use, not overdose,
and multiple drugs, including carbamazepine, diphenhydramine,
cyclobenzaprine, and quetiapine cross-react with qualitative
immunoassays, potentially yielding false positive results [36-39].
Quantitative serum concentrations are not only poor predictors of
systemic toxicity, due to the kinetic changes described above, but are
usually not available within a clinically relevant time frame [26]. (See
'Pharmacology' above.)
For all these reasons, we do not advocate the use of any numerical level
to gauge toxicity. The clinical picture dictates the need for therapy in
TCA overdose; clinicians should not be falsely reassured by a low serum
drug concentration, nor should they initiate therapy solely on the basis
of a high serum drug concentration.

DIAGNOSIS

The diagnosis of TCA poisoning is primarily made on clinical evaluation

due to the limitations of quantitative and qualitative testing. Clinically,
the diagnosis of TCA poisoning is made based upon a history of
ingestion, symptoms and signs consistent with the diagnosis, and
characteristic ECG findings.
Signs of TCA poisoning typically include sedation, but may also include
confusion, delirium, or hallucinations. Sinus tachycardia and other
arrhythmias, hypotension, cardiac conduction delays, and
anticholinergic toxicity (hyperthermia, flushing, dilated pupils, intestinal
ileus, urinary retention, and sinus tachycardia) are also common. Of
note, patients with TCA poisoning can appear stable but deteriorate
rapidly, and significant toxicity can occur despite falsely reassuring ECG
findings.
ECG findings suggestive of cardiotoxicity include: prolongation of the
QRS >100 msec; abnormal morphology of the QRS (eg, deep, slurred S
wave in leads I and aVL); and, abnormal size and ratio of the R and S
waves in lead aVR (R wave in aVR >3 mm; R to S ratio in aVR >0.7), or
possibly a Brugada pattern.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of patients presenting with toxicity from

tricyclic antidepressants (TCAs) is broad given the range of clinical
findings (decreased level of consciousness, seizures, anticholinergic
effects, hypotension, and widening of the QRS interval) associated with
this poisoning. In addition to being common in TCA toxicity, these
findings are associated with a number of other poisonings:
● Decreased level of consciousness may be caused by sedative-
hypnotic drugs, anti-epileptic drugs, alcohols, opioids and opiates,
 carbon monoxide, cyanide and hydrogen sulfide, and
antipsychotics;
● Seizures may be seen with cocaine, salicylates, methylxanthines
(caffeine and theophylline), metals (eg, lead), and other therapeutic
agents such as bupropion, tramadol, propoxyphene and baclofen;
● Anticholinergic effects (primarily muscarinic) may be sequelae of
poisoning from diphenhydramine and other antihistamines,
carbamazepine, cyclobenzaprine, amantadine, clozapine,
phenothiazines, procainamide, quinidine, and trihexyphenidyl,
among others;
● Hypotension with reflex tachycardia may result from poisoning
from various antihypertensives, such as alpha-adrenoreceptor
antagonists, nitrates, and dihydropyridine calcium channel
antagonists (such as nifedipine, nimodipine, amlodipine and
felodipine);
● QRS widening may be due to other sodium channel antagonists,
such as diphenhydramine, phenytoin, propoxyphene, cocaine and
the class 1A and 1C Vaughn Williams antiarrhythmics.
Generally speaking, it is the constellation of the above findings
(particularly depressed mental status, peripheral anticholinergic signs,
and evidence of sodium channel antagonism on ECG) that strongly
suggests TCA poisoning, although not all findings need to be present to
make the diagnosis.
Other drugs that can mimic this specific clinical picture include
diphenhydramine and possibly carbamazepine, although the former is
less known for depressed mental status and controversy exists
regarding the risk of fatal arrhythmias [40].

MANAGEMENT

Initial resuscitation — Initial management of the patient with a

tricyclic antidepressant (TCA) overdose centers on evaluating and, if
necessary, securing the patient's airway, breathing, and circulation. TCA
poisoned patients are frequently moribund and require intubation for
airway protection and ventilation. In hypotensive patients, avoid
induction agents that may worsen hypotension. Supplemental oxygen
should be administered as needed. A summary table to facilitate the
emergent management of TCA overdose is provided ( table 1).
Initial resuscitation includes the following measures:
● Sodium bicarbonate to treat cardiac toxicity, as manifested by a
prolonged QRS complex or ventricular arrhythmia. (See 'Sodium
bicarbonate for cardiac toxicity' below.)
● Isotonic saline given as intravenous (IV) boluses to treat
hypotension. IV boluses of 250 to 500 mL can be given and
repeated based upon patient response.
● Benzodiazepines for control of agitation and seizures. We suggest
lorazepam (1 mg IV) or diazepam (5 mg IV), repeated at 5 to 10
minute intervals as needed. Benzodiazepines should be used
judiciously, as agitation can rapidly give way to profound sedation
(from antihistaminic effects).
Despite prominent anticholinergic toxicity in some patients with TCA
poisoning, physostigmine is contraindicated as it is associated with
cardiac arrest in the setting of TCA toxicity [41]. (See 'Unhelpful and
contraindicated therapies' below.)
Frequent reassessment of patients with known or suspected TCA
intoxication is essential, as their level of alertness can change quickly.
Patients may manifest psychomotor agitation and delirium in the initial
hours after ingestion, only to develop progressive obtundation and
coma in later stages. Thus, close monitoring, including pulse oximetry
and a cardiac monitor, is necessary. In patients requiring treatment
with sodium bicarbonate, an arterial line makes it easier to perform
frequent pH testing.
Sodium bicarbonate for cardiac toxicity — Sodium bicarbonate is the
standard initial therapy for hypotension or arrhythmia due to TCA
toxicity. Sodium bicarbonate therapy is indicated in patients with TCA
poisoning who develop widening of the QRS interval >100 msec or a
ventricular arrhythmia.
The initial dose of hypertonic sodium bicarbonate is 1 to 2 mEq/kg,
given as a rapid IV push through a large bore IV catheter. In adults, one
common approach is to give two to three vials or prefilled syringes (50
mL each) of 8.4 percent sodium bicarbonate. If there is no response to
the initial dose, it may be repeated after five minutes. It is useful to run
a continuous 12-lead ECG during the infusion to demonstrate the
presence (or absence) of narrowing of the QRS complex, a decrease in
the R wave amplitude in lead aVR, or resolution of any arrhythmia
( waveform 1 and figure 2).
If the QRS narrows after bolus therapy, begin a continuous IV infusion
of sodium bicarbonate. We administer a solution of 150 mEq of sodium
bicarbonate in 1 L of 5 percent dextrose (D5W) infused at 250 mL/hour
in adults. The same fluid should be given to children at twice their
maintenance fluid rate. The sodium bicarbonate solution can be mixed
by adding 150 mEq sodium bicarbonate to D5W. Care should be taken
to remove the appropriate amount of fluid volume from the D5W bag
prior to adding sodium bicarbonate solution.
Should a widened QRS interval fail to narrow following bolus therapy
with sodium bicarbonate, we still suggest that an IV infusion of sodium
bicarbonate be started, absent an alternative diagnosis. Failure of a
widened QRS to respond to bolus therapy does not exclude the
possibility of TCA toxicity, and systemic acidemia potentiates the effects
of TCA poisoning [42].
Frequent arterial blood pH measurements should be obtained during
treatment with sodium bicarbonate. We recommend a goal pH of 7.50
to 7.55. Volume overload, hypokalemia, hypernatremia, and metabolic
alkalosis may result from prolonged bicarbonate infusions, and clinical
and laboratory parameters must be followed closely to avoid these
complications [43]. We measure the arterial pH hourly until it is the
therapeutic range and stable. Thereafter, measurements may be
obtained every four to six hours. The serum potassium concentration
should be measured concurrently with the arterial pH.
Most toxicologists taper bicarbonate therapy after the resolution of
ECG changes, which may occur over hours to days. One reasonable
approach is to reduce the infusion rate by about 25 percent per hour
over four hours. Should the QRS interval widen during tapering, give an
additional bolus of sodium bicarbonate as above and restart the
original infusion rate.
Some toxicologists and poison centers recommend against using a
sodium bicarbonate drip and favor using repeat boluses of sodium
bicarbonate in response to ECG changes. However, the bulk of clinical
experience favors the use of a continuous infusion, and this remains
the recommendation of the author [44].
Most patients with TCA-induced QRS interval prolongation appear to
respond to sodium bicarbonate therapy. According to retrospective
case series, 80 percent of patients with an increased QRS interval
demonstrated a decrease in response to treatment, while 90 percent of
hypotensive patients increased their blood pressure [42,45].
The benefit of sodium bicarbonate is probably due to both an increase
in serum pH and the increase in extracellular sodium. The increase in
serum pH favors the neutral (ie, non-ionized) form of the drug, making
it less available to bind to sodium channels [44,46]. Increasing the
extracellular sodium concentration increases the electrochemical
gradient across cardiac cell membranes, potentially attenuating the
TCA-induced blockade of rapid sodium channels (see 'Pharmacology'
above). The rationale for this therapy is based in part upon studies
using animal models of TCA poisoning showing that hypertonic sodium
bicarbonate narrows the QRS complex, improves systolic blood
pressure, and controls ventricular arrhythmias [45-50]. However, there
is a conspicuous absence of randomized trials in humans, and most
evidence of efficacy is based upon clinical experience [42,50].
We do not perform tracheal intubation for the purpose of
hyperventilation or routinely hyperventilate intubated patients as a
means to achieve serum alkalinization. Hyperventilation increases
serum pH by reducing pCO2. In a retrospective case series, decreasing
pCO2 (to a mean 36 mmHg) along with administration of sodium
bicarbonate led to a more rapid reduction in QRS duration and greater
increase in serum pH [51]. However, given the paucity of data, we do
not consider this a routine practice, although we agree that careful
attention to prevention of hypercarbia and the associated respiratory
acidosis is important.
Anti-seizure therapy — Benzodiazepines remain the treatment of
choice for TCA-induced seizures. Reasonable initial treatment options
include diazepam 5 mg IV, or lorazepam 2 mg IV. (See "Initial
management of the critically ill adult with an unknown overdose",
section on '"D": Disability and neurological stabilization' and
"Convulsive status epilepticus in adults: Management", section on 'In-
hospital treatment'.)
TCA-induced seizures are likely caused largely by central GABA-A
receptor inhibition. It is therefore logical to treat seizures with
benzodiazepines, which act on GABA-A receptors, rather than
antiepileptic medications acting on sodium channels, notably
phenytoin. Data from various animal models of drug-induced seizure as
well as clinical experience support this approach [52]. In the unusual
case that benzodiazepines are ineffective, barbiturates may be used to
control seizures. However, they are considered second-line therapy due
to their adverse effects upon blood pressure. Lastly, propofol, which
acts both on GABA receptors and NMDA receptors, may be used [52].
Levetiracetam has been proposed for the management of drug-
induced seizures, and evidence of its effectiveness following TCA
overdose is found in small retrospective case series [52,53]. Given the
limited data, we generally do not recommend levetiracetam, but it may
be used in cases refractory to all other interventions.
Gastrointestinal decontamination — After the airway, breathing, and
circulation have been secured, attention may be turned to
gastrointestinal decontamination. Unless bowel obstruction, ileus, or
perforation is suspected, we suggest treatment with 1 g/kg of activated
charcoal (maximum dose 50 g) in patients who present within two
hours of ingestion. Charcoal should be withheld in patients who are
sedated and may not be able to protect their airway, unless tracheal
intubation is performed first. However, tracheal intubation should not
be performed solely for the purpose of giving charcoal [54,55]. (See
"Gastrointestinal decontamination of the poisoned patient".)
As a general rule, we do not recommend whole bowel irrigation or
multidose charcoal as these have not been shown to improve
outcomes. Gastric lavage may be contraindicated in the setting of
arrhythmias due to increased vagal tone.
Management of refractory toxicity — Sodium bicarbonate remains
the mainstay of treatment for antiarrhythmia or hypotension related to
TCA poisoning. In the uncommon circumstance that sodium
bicarbonate and other initial resuscitative measures are ineffective,
several alternative treatments are available. These are described below,
along with several proposed treatments that should be avoided.
There are no clear, established criteria for determining when sodium
bicarbonate therapy has failed and adjunct therapy should be given.
One reasonable approach is to begin giving adjunct therapies to any
patient who remains hypotensive with a wide QRS interval despite
treatment with sodium bicarbonate that includes two separate bolus
doses and adequate alkalinization with a sodium bicarbonate infusion,
as described above. Because refractory toxicity is uncommon and
suggests that the patient will be difficult to manage, we recommend
consultation with a medical toxicologist or poison center in such cases.
(See 'Sodium bicarbonate for cardiac toxicity' above and 'Additional
resources' below.)
Refractory hypotension
Vasopressors — Vasopressors are indicated in patients with
hypotension refractory to sodium bicarbonate and aggressive IV fluid
resuscitation therapy. Direct-acting alpha adrenergic agonists (eg,
norepinephrine or phenylephrine) are preferred because they counter
the alpha adrenergic antagonist effects of TCAs. The IV infusion of the
selected vasopressor is titrated to effect.
A small retrospective study of TCA-poisoned patients demonstrated a
universal response to norepinephrine infusion, including patients who
had previously failed to respond to dopamine infusion [56].
Hypertonic (3 percent) saline — We suggest that hypertonic
saline be used only when hypotension is refractory to all other first line
treatments, including sodium bicarbonate and aggressive fluid
resuscitation. Patients who remain unstable following adequate
alkalinization, as determined by arterial pH, and whose hypotension
has failed to improve despite aggressive IV fluid resuscitation and
treatment with a direct acting vasopressor (eg, norepinephrine) may be
treated with hypertonic saline. We give a 100 mL IV bolus of 3 percent
saline; if symptoms persist, two more doses can be given at ten minute
intervals. No additional hypertonic saline should be given and the
serum sodium concentration should be monitored.
Some toxicologists advocate hypertonic (3 percent) saline as an
alternative to sodium bicarbonate therapy. However, reports about its
effectiveness are conflicting and there is no clear benefit over sodium
bicarbonate. Hypertonic saline therapy improves hypotension, but, with
the exception of one case report, there is little evidence that it improves
arrhythmias [57].
Refractory arrhythmias
Magnesium — We do not recommend magnesium as a first line
therapy for TCA poisoning, but it may be used as an adjunct treatment
in patients whose arrhythmia is unresponsive to sodium bicarbonate.
There are no standard dosing recommendations for magnesium in this
setting. One reasonable approach is to give 1 to 2 g over 15 minutes or
faster, if the patient is in cardiac arrest.
A randomized trial, several case reports, and animal studies support
the use of IV magnesium to help control arrhythmias caused by TCA
poisoning but refractory to sodium bicarbonate therapy [58-60]. In a
randomized trial of 72 patients with TCA poisoning, those treated with
magnesium in addition to sodium bicarbonate therapy experienced
lower mortality than those treated with sodium bicarbonate alone [61].
Lidocaine — Lidocaine (Class IB) has been used to treat TCA
poisoning with some encouraging results, but we do not advocate its
routine use as a first line therapy [62,63]. We suggest lidocaine only be
considered when sodium bicarbonate therapy is ineffective (ie,
arrhythmia persists). Should lidocaine be needed, we suggest standard
anti-arrhythmic doses, including a bolus dose (1 to 1.5 mg/kg IV),
followed by an infusion (1 to 4 mg/minute). Phenytoin, another Class IB
agent, has been studied in TCA poisoning but its use is controversial
and not generally recommended. (See 'Unhelpful and contraindicated
therapies' below.)
Severe hemodynamic instability and impending cardiac arrest
Lipid emulsion — Lipid emulsion has been used to counteract the
activity of lipophilic drugs in overdose, including TCAs [64-69]. Reports
suggest that lipid therapy following TCA overdose is associated with
reduced QTc prolongation, sedation, and seizure activity [70,71]. The
mechanism, evidence, dosing, and side effects of IV lipid emulsion
therapy are discussed in detail separately. (See "Calcium channel
blocker poisoning", section on 'Lipid emulsion therapy'.)
While clear indications have not been established, lipid therapy may be
used in patients with a TCA overdose who do not respond to standard
therapies, including sodium bicarbonate, and remain unstable, and in
patients who sustain a cardiac arrest. We recommend consultation with
a medical toxicologist or poison center whenever possible prior to
initiating lipid therapy.
The dosing protocol most widely reported is an IV bolus of 1 to 1.5
mL/kg of a 20 percent lipid emulsion solution given over one minute.
The same dose may be repeated in cases of cardiac arrest every three
to five minutes, for a total of three bolus doses. Following the initial
bolus, an infusion is started at a rate of 0.025 mL/kg per minute until
hemodynamic recovery occurs. In the event that hemodynamic
instability persists, the drip may be continued for one hour, with a
maximum dose of 8 mL/kg over that hour and 12.5 mL/kg in a 24-hour
span. Care must be taken to adhere to proper dosing as large volumes
of lipid can erroneously be administered rapidly.
Other potential therapies
● Cardiac pacing – Although rarely used for TCA poisoning, cardiac
pacing has been used successfully for an unusual case of junctional
bradycardia following imipramine ingestion [72].
● Extracorporeal membrane oxygenation (ECMO) – There are case
reports of patients with refractory hypotension after TCA overdose
recovering with venoarterial (VA) ECMO [73]. (See "Extracorporeal
life support in adults in the intensive care unit: Overview" and
"Extracorporeal life support in adults: Management of venoarterial
extracorporeal membrane oxygenation (V-A ECMO)".)
Unhelpful and contraindicated therapies
Enhanced elimination — Several case reports describe the successful
use of various therapies for TCA toxicity, including plasma exchange,
continuous kidney replacement with a commercial absorbent in the
circuit (CytoSorb), and charcoal hemoperfusion [74-78]. However, these
are generally isolated cases and it is difficult to determine efficacy, as
well as whether co-ingestants were involved. In general, interventions
to enhance drug elimination are not likely to be effective due to the
large volume of distribution of TCAs, and plasma exchange and
hemoperfusion are not recommended [79].
Medications — Flumazenil is contraindicated in patients with known
or suspected TCA use. In patients who acutely coingest TCAs and
benzodiazepines, flumazenil may lower the seizure threshold. In
patients with an isolated TCA ingestion who use benzodiazepines
chronically, flumazenil can induce benzodiazepine-withdrawal seizures.
Despite prominent anticholinergic toxicity in some patients with TCA
poisoning, physostigmine is contraindicated as it is associated with
cardiac arrest in the setting of TCA toxicity [41].
With the exception of lidocaine and magnesium (discussed above),
concerns surround the use of all classes of antiarrhythmic drugs in the
setting of TCA poisoning. Class IA (eg, procainamide) and Class IC
agents (eg, flecainide) are contraindicated given their inhibition of
rapid sodium channels, an effect similar to that induced by TCAs. Class
III agents (eg, amiodarone) are poorly studied in this setting and the
QTc prolongation associated with these drugs makes them potentially
dangerous. Although a Class IB agent like lidocaine, phenytoin is
generally not recommended in the setting of TCA poisoning. (See
"Cardiac excitability, mechanisms of arrhythmia, and action of
antiarrhythmic drugs".)
Pediatric considerations — TCA poisoning in the pediatric population
generally follows a course similar to that in adults, and the above-
mentioned assessment and treatment recommendations apply. In any
pediatric ingestion, health care workers should ascertain how the child
got access to the medication, as well as counseling caregivers
regarding medication safety as appropriate.
Disposition — Patients with an alteration in mental status,
hypotension, cardiac conduction abnormalities, or seizures should be
admitted to an intensive care unit. Patients with mild symptoms, such
as an isolated tachycardia without evidence of conduction
abnormalities (ie, QRS <100 msec) over several hours of observation,
could conceivably be admitted to a non-intensive care setting with
cardiac monitoring. Asymptomatic patients who manifest no
conduction abnormalities on ECG and are monitored for at least six
hours in an acute care setting can be safely discharged or transferred
to a psychiatric service for evaluation. (See "Suicidal ideation and
behavior in adults".)

ADDITIONAL RESOURCES

Regional poison centers — Regional poison centers in the United

States are available at all times for consultation on patients with known
or suspected poisoning, and who may be critically ill, require
admission, or have clinical pictures that are unclear (1-800-222-1222). In
addition, some hospitals have medical toxicologists available for
bedside consultation. Whenever available, these are invaluable
resources to help in the diagnosis and management of ingestions or
overdoses. Contact information for poison centers around the world is
provided separately. (See "Society guideline links: Regional poison
centers".)
Society guideline links — Links to society and government-sponsored
guidelines from selected countries and regions around the world are
provided separately. (See "Society guideline links: General measures for
acute poisoning treatment" and "Society guideline links: Treatment of
acute poisoning caused by specific agents other than drugs of abuse".)

SUMMARY AND RECOMMENDATIONS

● Clinical features of overdose – Overdose of a tricyclic
antidepressant (TCA) can be life threatening. Symptoms and signs
of TCA intoxication generally consist of vital sign abnormalities,
mental status changes, seizures, and anticholinergic toxicity. Sinus
tachycardia and hypotension are common. Sedation is the most
typical alteration in mental status, but confusion, delirium, or
hallucinations may occur. Anticholinergic toxicity commonly
manifests as hyperthermia, flushing, dilated pupils that respond
poorly to light, delirium, intestinal ileus, and urinary retention. (See
'Clinical features' above and "Anticholinergic poisoning".)
The clinical course of patients with TCA poisoning can be
unpredictable, and patients who present immediately after
ingestion may initially be well appearing, only to deteriorate
rapidly. Patients must be closely monitored. Maprotiline has been
associated with a greater frequency of seizures and arrhythmias
than other TCAs. (See 'Overview of physical findings' above.)
● Electrocardiogram (ECG) changes with toxicity – Cardiac
conduction abnormalities are common in patients with TCA
poisoning. These abnormalities can degenerate into ventricular
 tachycardia (VT) and ventricular fibrillation (VF), which occur in
approximately 4 percent of TCA overdose cases. The ECG is the
most valuable tool in determining the extent of TCA poisoning. The
following signs suggest cardiotoxicity (see 'Cardiovascular toxicity'
above and 'Electrocardiogram' above):
• Prolongation of the QRS >100 msec
• Abnormal morphology of the QRS (eg, deep, slurred S wave in
leads I and aVL)
• Abnormal size and ratio of the R and S waves in lead aVR: R wave
in aVR >3 mm; R to S ratio in aVR >0.7
● Diagnosis – The diagnosis of TCA poisoning is made clinically
based upon a history of ingestion, symptoms and signs consistent
with the diagnosis, and characteristic ECG findings. Serum
measurements of TCA concentrations or qualitative screening tests
are typically not available to clinicians in a timely fashion and
seldom play a role in patient management. (See 'Diagnosis' above
and 'Differential diagnosis' above.)
● General management – Most patients respond well to standard
care. A summary table to facilitate the emergency management of
TCA overdose is provided ( table 1). (See 'Management' above.)
Initial treatment of TCA overdose includes assessing and securing
the patient's airway, breathing, and circulation. TCA poisoned
patients are frequently moribund and require intubation for airway
protection and ventilation. Intravenous (IV) boluses of isotonic
saline are used to treat hypotension. (See 'Initial resuscitation'
above.)
 Physostigmine, class 1A/1C antiarrhythmic agents (eg,
procainamide, flecainide), and flumazenil are contraindicated.
Despite prominent anticholinergic toxicity in some patients,
physostigmine is associated with cardiac arrest in the setting of
TCA toxicity. (See 'Unhelpful and contraindicated therapies' above.)
● Role of gastrointestinal decontamination – In patients who
present within two hours of TCA ingestion and have no suspicion
for bowel obstruction, ileus, or perforation, we suggest treatment
with activated charcoal (Grade 2C). We use 1 g/kg (maximum dose
50 g) orally. (See 'Gastrointestinal decontamination' above.)
● Cardiac toxicity – In patients with TCA poisoning with ECG
demonstrating QRS duration >100 msec or any ventricular
arrhythmia, we recommend sodium bicarbonate therapy (Grade
1B). The initial dose of sodium bicarbonate is 1 to 2 mEq/kg IV. In
adults, this may be given as two to three 50 mEq (50 mL) vials or
prefilled syringes of 8.4% sodium bicarbonate given as a rapid IV
push through a large-bore IV. (See 'Sodium bicarbonate for cardiac
toxicity' above.)
● Seizures – We use benzodiazepines to treat TCA-induced seizures.
Reasonable initial options in adults include diazepam 5 mg IV or
lorazepam 2 mg IV. (See 'Anti-seizure therapy' above.)
● Refractory toxicity – In the uncommon circumstance that sodium
bicarbonate and other initial resuscitative measures are ineffective,
the following are alternative treatments (see 'Management of
refractory toxicity' above):
 • Refractory hypotension: norepinephrine infusion, hypertonic
saline
• Refractory arrhythmias: magnesium, lidocaine
• Impending cardiac arrest: lipid emulsion infusion
REFERENCES

1. Wong J, Motulsky A, Abrahamowicz M, et al. Off-label indications for

antidepressants in primary care: descriptive study of prescriptions
from an indication based electronic prescribing system. BMJ 2017;
356:j603.
2. Franssen EJ, Kunst PW, Bet PM, et al. Toxicokinetics of nortriptyline
and amitriptyline: two case reports. Ther Drug Monit 2003; 25:248.
3. Lynch R. Tricyclic antidepressant overdose. Emerg Med J 2002;
19:596.
4. Kerr GW, McGuffie AC, Wilkie S. Tricyclic antidepressant overdose: a
review. Emerg Med J 2001; 18:236.
5. Jarvis MR. Clinical pharmacokinetics of tricyclic antidepressant
overdose. Psychopharmacol Bull 1991; 27:541.
6. Spiker DG, Biggs JT. Tricyclic antidepressants. Prolonged plasma
levels after overdose. JAMA 1976; 236:1711.
7. van de Wint T, de Vries Schultink AHM, Meinders AJ, et al. Prolonged
coma due to amitriptyline overdose and genetic polymorphism: a
case report. J Med Case Rep 2022; 16:112.
8. Glassman AH. Cardiovascular effects of tricyclic antidepressants.
Annu Rev Med 1984; 35:503.
 9. Pentel P, Benowitz N. Efficacy and mechanism of action of sodium
bicarbonate in the treatment of desipramine toxicity in rats. J
Pharmacol Exp Ther 1984; 230:12.
10. Merigian KS, Hedges JR, Kaplan LA, et al. Plasma catecholamine
levels in cyclic antidepressant overdose. J Toxicol Clin Toxicol 1991;
29:177.
11. Biggs JT, Spiker DG, Petit JM, Ziegler VE. Tricyclic antidepressant
overdose: incidence of symptoms. JAMA 1977; 238:135.
12. Glauser J. Tricyclic antidepressant poisoning. Cleve Clin J Med 2000;
67:704.
13. Liebelt EL. Chapter 73: Cyclic antidepressants. In: Goldfrank's Toxicol
ogic Emergencies, 9th ed, Nelson LS (Ed), McGraw-Hill, New York 201
1.
14. Callaham M, Kassel D. Epidemiology of fatal tricyclic antidepressant
ingestion: implications for management. Ann Emerg Med 1985;
14:1.
15. Shannon M, Merola J, Lovejoy FH Jr. Hypotension in severe tricyclic
antidepressant overdose. Am J Emerg Med 1988; 6:439.
16. Goldberg RJ, Capone RJ, Hunt JD. Cardiac complications following
tricyclic antidepressant overdose. Issues for monitoring policy. JAMA
1985; 254:1772.
17. Olson KR, Kearney TE, Dyer JE, et al. Seizures associated with
poisoning and drug overdose. Am J Emerg Med 1994; 12:392.
18. Citak A, Soysal DD, Uçsel R, et al. Seizures associated with poisoning
in children: tricyclic antidepressant intoxication. Pediatr Int 2006;
 48:582.
19. Ellison DW, Pentel PR. Clinical features and consequences of seizures
due to cyclic antidepressant overdose. Am J Emerg Med 1989; 7:5.
20. Taboulet P, Michard F, Muszynski J, et al. Cardiovascular
repercussions of seizures during cyclic antidepressant poisoning. J
Toxicol Clin Toxicol 1995; 33:205.
21. Knudsen K, Heath A. Effects of self poisoning with maprotiline. Br
Med J (Clin Res Ed) 1984; 288:601.
22. Harrigan RA, Brady WJ. ECG abnormalities in tricyclic antidepressant
ingestion. Am J Emerg Med 1999; 17:387.
23. Niemann JT, Bessen HA, Rothstein RJ, Laks MM. Electrocardiographic
criteria for tricyclic antidepressant cardiotoxicity. Am J Cardiol 1986;
57:1154.
24. Brahmi N, Thabet H, Kouraichi N, et al. [Brugada syndrome and
other cardiovascular abnormalities related to tricyclic
antidepressants ans related drugs intoxication]. Arch Mal Coeur
Vaiss 2007; 100:28.
25. Bebarta VS, Waksman JC. Amitriptyline-induced Brugada pattern
fails to respond to sodium bicarbonate. Clin Toxicol (Phila) 2007;
45:186.
26. Boehnert MT, Lovejoy FH Jr. Value of the QRS duration versus the
serum drug level in predicting seizures and ventricular arrhythmias
after an acute overdose of tricyclic antidepressants. N Engl J Med
1985; 313:474.
27. Foulke GE, Albertson TE. QRS interval in tricyclic antidepressant
overdosage: inaccuracy as a toxicity indicator in emergency settings.
Ann Emerg Med 1987; 16:160.
28. Buckley NA, O'Connell DL, Whyte IM, Dawson AH. Interrater
agreement in the measurement of QRS interval in tricyclic
antidepressant overdose: implications for monitoring and research.
Ann Emerg Med 1996; 28:515.
29. Liebelt EL, Ulrich A, Francis PD, Woolf A. Serial electrocardiogram
changes in acute tricyclic antidepressant overdoses. Crit Care Med
1997; 25:1721.
30. Liebelt EL, Francis PD, Woolf AD. ECG lead aVR versus QRS interval in
predicting seizures and arrhythmias in acute tricyclic antidepressant
toxicity. Ann Emerg Med 1995; 26:195.
31. Caravati EM, Bossart PJ. Demographic and electrocardiographic
factors associated with severe tricyclic antidepressant toxicity. J
Toxicol Clin Toxicol 1991; 29:31.
32. Simon M, Kaplan S, Muschler K, et al. The role of QRS complex
prolongation in predicting severe toxicity in single-xenobiotic
overdose. Clin Toxicol (Phila) 2024; 62:32.
33. Wolfe TR, Caravati EM, Rollins DE. Terminal 40-ms frontal plane QRS
axis as a marker for tricyclic antidepressant overdose. Ann Emerg
Med 1989; 18:348.
34. Petit JM, Spiker DG, Ruwitch JF, et al. Tricyclic antidepressant plasma
levels and adverse effects after overdose. Clin Pharmacol Ther 1977;
21:47.
35. Spiker DG, Weiss AN, Chang SS, et al. Tricyclic antidepressant
overdose: clinical presentation and plasma levels. Clin Pharmacol
Ther 1975; 18:539.
36. Chattergoon DS, Verjee Z, Anderson M, et al. Carbamazepine
interference with an immune assay for tricyclic antidepressants in
plasma. J Toxicol Clin Toxicol 1998; 36:109.
37. Fleischman A, Chiang VW. Carbamazepine overdose recognized by a
tricyclic antidepressant assay. Pediatrics 2001; 107:176.
38. Hendrickson RG, Morocco AP. Quetiapine cross-reactivity among
three tricyclic antidepressant immunoassays. J Toxicol Clin Toxicol
2003; 41:105.
39. Sloan KL, Haver VM, Saxon AJ. Quetiapine and false-positive urine
drug testing for tricyclic antidepressants. Am J Psychiatry 2000;
157:148.
40. Sharma AN, Hexdall AH, Chang EK, et al. Diphenhydramine-induced
wide complex dysrhythmia responds to treatment with sodium
bicarbonate. Am J Emerg Med 2003; 21:212.
41. Pentel P, Peterson CD. Asystole complicating physostigmine
treatment of tricyclic antidepressant overdose. Ann Emerg Med
1980; 9:588.
42. Hoffman JR, Votey SR, Bayer M, Silver L. Effect of hypertonic sodium
bicarbonate in the treatment of moderate-to-severe cyclic
antidepressant overdose. Am J Emerg Med 1993; 11:336.
43. Chan BS, Buckley NA. Common pitfalls in the use of hypertonic
sodium bicarbonate for cardiac toxic drug poisonings. Clin Toxicol
 (Phila) 2024; 62:213.
44. Bruccoleri RE, Burns MM. A Literature Review of the Use of Sodium
Bicarbonate for the Treatment of QRS Widening. J Med Toxicol 2016;
12:121.
45. Blackman K, Brown SG, Wilkes GJ. Plasma alkalinization for tricyclic
antidepressant toxicity: a systematic review. Emerg Med (Fremantle)
2001; 13:204.
46. Sasyniuk BI, Jhamandas V. Mechanism of reversal of toxic effects of
amitriptyline on cardiac Purkinje fibers by sodium bicarbonate. J
Pharmacol Exp Ther 1984; 231:387.
47. Sasyniuk BI, Jhamandas V, Valois M. Experimental amitriptyline
intoxication: treatment of cardiac toxicity with sodium bicarbonate.
Ann Emerg Med 1986; 15:1052.
48. McCabe JL, Cobaugh DJ, Menegazzi JJ, Fata J. Experimental tricyclic
antidepressant toxicity: a randomized, controlled comparison of
hypertonic saline solution, sodium bicarbonate, and
hyperventilation. Ann Emerg Med 1998; 32:329.
49. Brown TC. Tricyclic antidepressant overdosage: experimental studies
on the management of circulatory complications. Clin Toxicol 1976;
9:255.
50. Brown TC. Sodium bicarbonate treatment for tricyclic antidepressant
arrhythmias in children. Med J Aust 1976; 2:380.
51. Pai K, Buckley NA, Isoardi KZ, et al. Optimising alkalinisation and its
effect on QRS narrowing in tricyclic antidepressant poisoning. Br J
Clin Pharmacol 2022; 88:723.
52. Chen HY, Albertson TE, Olson KR. Treatment of drug-induced
seizures. Br J Clin Pharmacol 2016; 81:412.
53. Lee T, Warrick BJ, Sarangarm P, et al. Levetiracetam in toxic seizures.
Clin Toxicol (Phila) 2018; 56:175.
54. Bosse GM, Barefoot JA, Pfeifer MP, Rodgers GC. Comparison of three
methods of gut decontamination in tricyclic antidepressant
overdose. J Emerg Med 1995; 13:203.
55. Roy TM, Ossorio MA, Cipolla LM, et al. Pulmonary complications
after tricyclic antidepressant overdose. Chest 1989; 96:852.
56. Tran TP, Panacek EA, Rhee KJ, Foulke GE. Response to dopamine vs
norepinephrine in tricyclic antidepressant-induced hypotension.
Acad Emerg Med 1997; 4:864.
57. McKinney PE, Rasmussen R. Reversal of severe tricyclic
antidepressant-induced cardiotoxicity with intravenous hypertonic
saline solution. Ann Emerg Med 2003; 42:20.
58. Citak A, Soysal DD, Uçsel R, et al. Efficacy of long duration
resuscitation and magnesium sulphate treatment in amitriptyline
poisoning. Eur J Emerg Med 2002; 9:63.
59. Knudsen K, Abrahamsson J. Effects of magnesium sulfate and
lidocaine in the treatment of ventricular arrhythmias in
experimental amitriptyline poisoning in the rat. Crit Care Med 1994;
22:494.
60. Knudsen K, Abrahamsson J. Magnesium sulphate in the treatment of
ventricular fibrillation in amitriptyline poisoning. Eur Heart J 1997;
18:881.
61. Emamhadi M, Mostafazadeh B, Hassanijirdehi M. Tricyclic
antidepressant poisoning treated by magnesium sulfate: a
randomized, clinical trial. Drug Chem Toxicol 2012; 35:300.
62. Pentel PR, Benowitz NL. Tricyclic antidepressant poisoning.
Management of arrhythmias. Med Toxicol 1986; 1:101.
63. Mayron R, Ruiz E. Phenytoin: does it reverse tricyclic-antidepressant-
induced cardiac conduction abnormalities? Ann Emerg Med 1986;
15:876.
64. Levine M, Brooks DE, Franken A, Graham R. Delayed-onset seizure
and cardiac arrest after amitriptyline overdose, treated with
intravenous lipid emulsion therapy. Pediatrics 2012; 130:e432.
65. Blaber MS, Khan JN, Brebner JA, McColm R. "Lipid rescue" for tricyclic
antidepressant cardiotoxicity. J Emerg Med 2012; 43:465.
66. Kiberd MB, Minor SF. Lipid therapy for the treatment of a refractory
amitriptyline overdose. CJEM 2012; 14:193.
67. Hendron D, Menagh G, Sandilands EA, Scullion D. Tricyclic
antidepressant overdose in a toddler treated with intravenous lipid
emulsion. Pediatrics 2011; 128:e1628.
68. Boegevig S, Rothe A, Tfelt-Hansen J, Hoegberg LC. Successful
reversal of life threatening cardiac effect following dosulepin
overdose using intravenous lipid emulsion. Clin Toxicol (Phila) 2011;
49:337.
69. Angel-Isaza AM, Bustamante-Cristancho LA, Uribe-B FL. Successful
Outcome Following Intravenous Lipid Emulsion Rescue Therapy in a
 Patient with Cardiac Arrest Due to Amitriptyline Overdose. Am J Case
Rep 2020; 21:e922206.
70. Matsuoka M, Imai T, Iwabuchi S, Kinoshita K. Successful Treatment
of Amoxapine-Induced Intractable Seizures With Intravenous Lipid
Emulsion. J Emerg Med 2023; 64:62.
71. Hwang Y, Sohn JT. Effect of lipid emulsion on neuropsychiatric drug-
induced toxicity: A narrative review. Medicine (Baltimore) 2024;
103:e37612.
72. Sert A, Aypar E, Odabas D, Aygul MU. Temporary cardiac pacemaker
in the treatment of junctional rhythm and hypotension due to
imipramine intoxication. Pediatr Cardiol 2011; 32:521.
73. Upchurch C, Blumenberg A, Brodie D, et al. Extracorporeal
membrane oxygenation use in poisoning: a narrative review with
clinical recommendations. Clin Toxicol (Phila) 2021; 59:877.
74. Kobayashi K, Miyajima M, Tanaka T, et al. [Tricyclic antidepressant
overdose rescued by percutanenous cardiopulmonary support:
report of two cases]. Chudoku Kenkyu 2011; 24:46.
75. Kolsal E, Tekin IO, Piskin E, et al. Treatment of severe amitriptyline
intoxication with plasmapheresis. J Clin Apher 2009; 24:21.
76. Mutlu M, Karagüzel G, Bahat E, et al. Charcoal hemoperfusion in an
infant with supraventricular tachycardia and seizures secondary to
amitriptyline intoxication. Hum Exp Toxicol 2011; 30:254.
77. Sari I, Turkcuer I, Erurker T, et al. Therapeutic plasma exchange in
amitriptyline intoxication: case report and review of the literature.
Transfus Apher Sci 2011; 45:183.
78. Paland M. Use of CytoSorb in cases of acute amitriptyline
intoxication. J Clin Pharm Ther 2021; 46:1476.
79. Yates C, Galvao T, Sowinski KM, et al. Extracorporeal treatment for
tricyclic antidepressant poisoning: recommendations from the
EXTRIP Workgroup. Semin Dial 2014; 27:381.
Topic 295 Version 32.0

© 2024 UpToDate, Inc. All rights reserved.