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.
You might also be interested in our medical flashcard collection which contains over 1000
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Aetiology
Pharmacology
TCAs act on multiple neurotransmitter pathways to enhance the effects of certain hormones
while inhibiting others.
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 effect.
● Postsynaptic receptor antagonism: this prevents the neurotransmitter from activating
the postsynaptic receptor, overall reducing its effect.
Table 1. An overview of the pathways affected by TCAs.2
Postsynaptic receptor antagonism
Reuptake inhibition (increased effect) (decreased effect)
● Serotonin (5-HT receptors) ● Histamine (H1 receptors)
● Noradrenaline (NA receptors) ● A-1 adrenoreceptors
● Acetylcholine receptors
, The key mechanism by which TCAs achieve their antidepressant effect is by inhibiting the
reuptake of serotonin and noradrenaline. However, the lack of specificity and effects on
other pathways results in an extensive side effect profile 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 effects being cardiovascular and
neurological instability. They have a 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
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.
You might also be interested in our medical flashcard collection which contains over 1000
flashcards that cover key medical topics.
Aetiology
Pharmacology
TCAs act on multiple neurotransmitter pathways to enhance the effects of certain hormones
while inhibiting others.
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 effect.
● Postsynaptic receptor antagonism: this prevents the neurotransmitter from activating
the postsynaptic receptor, overall reducing its effect.
Table 1. An overview of the pathways affected by TCAs.2
Postsynaptic receptor antagonism
Reuptake inhibition (increased effect) (decreased effect)
● Serotonin (5-HT receptors) ● Histamine (H1 receptors)
● Noradrenaline (NA receptors) ● A-1 adrenoreceptors
● Acetylcholine receptors
, The key mechanism by which TCAs achieve their antidepressant effect is by inhibiting the
reuptake of serotonin and noradrenaline. However, the lack of specificity and effects on
other pathways results in an extensive side effect profile 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 effects being cardiovascular and
neurological instability. They have a 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
