11/14/24, 10\:40 AM Tricyclic Antidepressant Overdose

Tricyclic Antidepressant Overdose

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Tricyclic antidepressants (TCAs)\: initially for severe depression, now rarely used in psychiatry; common in managing
neuropathic pain and migraine prophylaxis (e.g., amitriptyline, nortriptyline, dosulepin).
Overdose\: highly toxic, commonly ingested in self-poisoning; 268 annual deaths in the UK from TCA overdose.
Pharmacology\: inhibits reuptake of serotonin and noradrenaline; antagonises histamine, alpha-1 adrenoreceptors,
acetylcholine receptors; a
Side e
gain), anticholinergic (dry mouth, confusion), alpha-1 adrenergic (hypotension).
Risk factors\: intentional overdose (suicide attempt), unintentional (elderly with cognitive impairment, unattended ingestion
by children).
Clinical features\: anticholinergic toxicity (dry mouth, confusion), sodium channel blockade (arrhythmias), severe e
(cardiovascular collapse, convulsions, coma).
Investigations\: basic observations, 12-lead ECG (widened QRS, prolonged QTc), blood glucose, blood gas (mixed acidosis),
FBC, U&Es, magnesium, LFTs, paracetamol and salicylate levels.
Diagnosis\: guided by history of ingestion, supported by collateral history from relatives/paramedics, and empty medication
boxes.
Management\: no speci
resuscitation follows ABCDE approach, intubation for airway protection, benzodiazepines for seizures.
Ongoing care\: monitor in emergency or ICU for severe toxicity; mental health assessment post-stabilization for intentional
overdose.
Complications\: death from cardiac/neurological e
reduced consciousness.
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Introduction

Tricyclic antidepressants (TCAs) are a class of medications developed initially for severe depression. However, the
development of newer antidepressants means TCAs are now rarely used in psychiatric conditions.
Despite this, TCAs remain a commonly prescribed medication in the community and are used to manage neuropathic
pain and for migraine prophylaxis. Examples of TCAs include amitriptyline, nortriptyline and dosulepin.
TCAs are a common substance ingested in self-poisoning and are highly toxic in overdose. They are second only to
analgesic drugs as the most commonly taken in fatal overdose. 1
An estimated 268 people die in the United Kingdom each
year following tricyclic antidepressant overdose.

Aetiology

Pharmacology

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TCAs act on multiple neurotransmitter pathways to enhance the e
There are two main mechanisms of action\:
Reuptake inhibition\: this prevents the neurotransmitter from being transported back into the pre-synaptic neurone once
released into the synaptic cleft. Subsequently, the neurotransmitter remains in the synaptic cleft and continues to
activate the postsynaptic receptor, increasing its e
Postsynaptic receptor antagonism\: this prevents the neurotransmitter from activating the postsynaptic receptor, overall
reducing its e
Table 1. An overview of the pathways a
2
Reuptake inhibition (increased ePostsynaptic receptor antagonism
(decreased e
Serotonin (5-HT receptors)
Noradrenaline (NA receptors)
Histamine (H1 receptors)
A-1 adrenoreceptors
Acetylcholine receptors
The key mechanism by which TCAs achieve their antidepressant e
noradrenaline. However, the lack of speci
and contributes to their toxicity in overdose.
The clinical manifestations of pathways involved are listed below\:
2
Serotonin\: nausea, gastrointestinal upset, sexual dysfunction
Noradrenaline\: tachycardia, tremors
Antihistamine\: sedation, weight gain
Anticholinergic\: dry mouth, blurred vision, confusion, constipation, tachycardia, urinary retention
Alpha-1 adrenergic\: postural hypotension, drowsiness, dizziness
TCAs also act on the fast sodium channels in myocardial cells, resulting in sodium channel blockade and risk of cardiac
arrhythmias, convulsions, and coma in overdose.

Risk factors

Intentional overdose

Most commonly, TCA overdose results from a suicide attempt or an act of self-harm. The patient may have a past
psychiatric history or have a history of previous overdoses.

Unintentional or accidental overdose

Unintentional/accidental overdose is less common in patients presenting with a TCA overdose as they are not available
over the counter.
However, there is a risk in the elderly population that those with cognitive impairment take more than their prescribed
doses of medication. Likewise, a child may ingest medication that is left unattended.

Clinical features

History

TCAs are highly toxic in overdose, the most severe e
narrow therapeutic window, with toxicity seen even with lower doses.
The clinical presentation can vary depending on severity. The clinical manifestations of overdose become apparent within
six hours of ingestion.
1
The key clinical features of TCA overdose include signs of anticholinergic toxicity and the result of sodium channel
blockade. Severe e
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Typical symptoms may include\:
Dry mouth
Hot, dry skin
Confusion and hallucinations
Palpitations
Other important areas to cover in the history include\:
History of ingestion\: ascertain how much of the medication has been ingested. A calculation of mg/kg ingestion can be
helpful prognostically. Explore whether the patient may have taken a mixed overdose and manage each substance
accordingly
Past medical history
Past psychiatric history
Collateral history is especially important if the patient has a reduced level of consciousness. Helpful information can be
gained from patients’ relatives or paramedics at the scene following the overdose. Paramedics may often bring empty
medication boxes to the hospital, which helps estimate ingestion.

Clinical examination

As with all acutely unwell patients, follow an ABCDE approach to the initial assessment and management.
TCA overdose has a spectrum of clinical presentations ranging from asymptomatic patients to those acutely unwell and
at risk of death.
Airway
There is a risk of airway compromise in patients who present with a reduced consciousness level and/or seizures. Signs of
airway compromise include snoring, secretions, and reduced respiratory rate/reduced SpO .
2
Basic airway manoeuvres can help in the acute setting, but typically patients with a GCS of 8 or below require intubation to
protect the airway.
Breathing
reduced SpO .
2
In patients presenting with severe toxicity, respiratory depression may occur resulting in reduced respiratory rate and
Circulation
TCAs cause myocardial sodium channel blockade resulting in hypotension and arrhythmia.
Tachycardia and peripheral vasodilation may occur because of serotonergic activity.
ECG
ventricular
Disability
Assess the conscious level, either using the AVPU scale or Glasgow coma scale. Presentation of TCA overdose can range
from confusion to seizures and coma.
Patients may present actively seizing or in a postictal state.
Don’t ever forget glucose, ensure all patients have bedside glucose checked to exclude hypoglycaemia.
Exposure
It is important to check temperature as patients may be hyperthermic due to serotonergic e
Look for anticholinergic signs including dry skin, eyes and mouth, urinary retention and ileus.
Co-ingestion with other medications which up-regulate serotonin increases the risk of serotonin syndrome.
Serotonin syndrome
Serotonin syndrome is a potentially life-threatening presentation precipitated by the overactivation of both central
and peripheral serotonin receptors. It is caused by using serotonergic drugs, which include TCAs, but also other
medications including SSRIs and some opioids.
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The hallmark features of serotonin syndrome are altered mental state, neuromuscular hyperactivity and
autonomic hyperactivity. Resultant clinical features are hypertension, tachycardia, diaphoresis, myoclonus and
hyperre
The diagnosis of serotonin syndrome is clinical and often involves the history of ingestion of serotonergic medication.
Management is largely supportive. Benzodiazepines are often used for sedation.
3

Investigations

Bedside investigations

Relevant bedside investigations include\:
Basic observations (vital signs)\: should be checked as part of the ABCDE assessment. Findings include tachycardia,
hypotension and hyperthermia.
12-lead ECG\: TCA toxicity causes serious and potentially fatal arrhythmias. Typical ECG
and prolonged QTc (Figure 1). Patients with an abnormal initial ECG are at risk of progressing to VF and VT
Blood glucose\: to exclude hypoglycaemia as a cause of presentation
Blood gas\: TCAs can cause mixed acidosis. Those with acidosis require speci
Figure 1. Typical ECG of TCA toxicity
demonstrating sinus tachycardia and
broad QRS complexes.

Laboratory investigations

Relevant laboratory investigations include\:
Full blood count\: to establish a baseline
Urea & electrolytes\: hypokalaemia is seen in TCA overdose. This can contribute to seizures or cardiac arrhythmias. TCAs
are renally excreted therefore patients with renal impairment may be at risk of more serious or prolonged toxicity.
Magnesium and bone pro
Liver function tests\: useful if there is a concern regarding co-ingestion of other medications, particularly paracetamol
Paracetamol and salicylate levels\: typically checked in all patients presenting with overdose, particularly where the
history is unclear

Imaging

There is no speci
investigations may be relevant\:
Chest X-ray\: useful in the assessment of patients who are presenting with reduced conscious level and airway
compromise, where there is a risk of aspiration pneumonia
CT head\: should be considered in patients with signi
May also be performed in those presenting with seizures.

Diagnosis

Most commonly, the diagnosis of TCA toxicity will be guided by the history of ingestion. In unresponsive patients, it is
important to gain a collateral history of the substances that may have been ingested. Information regarding this can be
gained from relatives, paramedics, or items on the patient (e.g. empty pill packets).
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Management

Acute management

There is no speci
Activated charcoal can be given to the conscious patient to prevent absorption if they present within one hour of
ingestion. Sodium bicarbonate can be given in arrhythmia and acidosis to prevent progression to ventricular arrhythmias.
1

Resuscitation

As with the assessment of the patient, follow the ABCDE approach to the initial management of TCA overdose
Airway
Simple airway manoeuvres or adjuncts can be used initially, however, those with signi
require intubation for de
Breathing
Administer high 2
monitoring
Circulation
ECG.
Establish intravenous access. Start continuous cardiac monitoring in all unwell patients or those with an abnormal initial
Administer
Disability
Assess and monitor the level of consciousness.
Benzodiazepines should be given for seizures. Phenytoin should be avoided due to its serotonergic e
Exposure
Cooling measures may be required to manage hyperpyrexia. Manage other speci
catheterise in urinary retention).
Capacity and Mental Health Act assessment
Patients presenting with an overdose may be confused or have a severe mental health illness resulting in an added
complexity to their care. They may refuse treatment or attempt to abscond from the emergency department.
Mental capacity should be assessed during the initial review. To be deemed capacious, patients must be able to
understand information, retain it, weigh up their decision and communicate their decision back to the clinician. If
any of these elements of capacity are not ful
interests.
If a patient is deemed to have capacity but remains a risk to their health, they may need to be detained under the
Mental Health Act. They will need a full Mental Health Act assessment in order to be detained, which is typically
performed by the hospital mental health team.
The hospital mental health team should be involved to assist in the assessment and management of patients
presenting with overdose.

Ongoing management

Patients with severe toxicity need to be managed in a monitored area in the emergency department and may need
intensive care unit admission for ongoing care.
Once medically stable, those who have presented with an intentional overdose require mental health assessment to
manage the underlying cause of their presentation.
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Complications

Ultimately, untreated TCA overdose can result in death secondary to cardiac or neurological e
activity can result in brain injury and coma. Those with reduced consciousness are at risk of aspiration pneumonia if their
airway is not managed e

References

Kerr GW, McGuLINK].
Westenberg HG. P h a r m a c o l o g y o f a n t i d e p r e s s a n t s \: s e l e c t i v i t y o r m u l t i p l i c i t y ? . Available from\: [LINK]
Volpi-Abadie, J, Kaye, AM, Kaye, AD. S e r o t o n i n S y n d r o m e . Available from [LINK]

Image references

Figure 1. Life in the Fast Lane. T r i c y c l i c o v e r d o s e . License\: [CC BY-NC-SA]

Reviewer

Dr Shariq Ahmed
Emergency Medicine Consultant

Related notes

Opioid Overdose
Paracetamol Overdose
Salicylate Overdose

Test yourself

Contents

Introduction
Aetiology
Risk factors
Clinical features
Investigations
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