Tricyclic antidepressants

Question 1

What is the mechanism of action of tricyclic antidepressants in the treatment of depression?

Answer 1

Non-specific blockers of presynaptic monoamine uptake - mostly serotonin (5-HT) and noradrenaline

Question 2

As well as serotonin, what neurotransmitters are affected by tricyclic antidepressants?

Answer 2

Muscarinic blockers

α-adrenergic blockers

Histamine blockers

Question 3

What is the most common indication for tricyclic antidepressants nowadays?

Answer 3

Neuropathic pain.

TCAs are now less commonly used for depression due to their side effects and toxicity in overdose. They are however used widely in the treatment of neuropathic pain, where smaller doses are typically required.

Question 4

Which patients with depression might we choose to give tricyclic antidepressants to instead of SSRIs?

Answer 4

Those in whom sedation would be beneficial, eg those experiencing insomnia or psychotic depression patients. SSRIs can make insomnia worse.

Question 5

What are the side effects of tricyclic antidepressants as a result of its anti-muscarinic properties?

Answer 5

Dry mouth

Constipation

Urinary retention

Blurred vision

Question 6

What are the side effects of tricyclic antidepressants as a result of its anti-histaminergic properties?

Answer 6

Weight gain

Sedation

Question 7

What are the side effects of tricyclic antidepressants as a result of its anti-α-adrenergic properties?

Answer 7

Postural hypotension

Question 8

What are the cardiotoxic side effects of tricyclic antidepressants?

Answer 8

QT interval prolongation

ST segment elevation

Heart block arrhythmias - due to noradrenaline uptake blocking in the heart

Question 9

Tricyclic antidepressants can be divided into those that are more or less sedative. What are the more sedative TCAs?

Answer 9

Amitriptyline

Clomipramine

Dosulepin

Question 10

Tricyclic antidepressants can be divided into those that are more or less sedative. What are the less sedative TCAs?

Answer 10

Imipramine

Lofepramine

Nortriptyline

Question 11

Which tricyclic antidepressant has the lowest incidence of toxicity in overdose?

Answer 11

Lofepramine

Question 12

Which two tricyclic antidepressants are particularly dangerous in overdose?

Answer 12

Amitriptyline

Dosulepin (dothiepin)

Question 13

What are the early features of tricyclic antidepressant overdose?

Answer 13

Relate mostly to anticholinergic properties:

Dry mouth

Dilated pupils

Agitation

Sinus tachycardia

Blurred vision

Question 14

What are the more severe features of tricyclic antidepressant overdose?

Answer 14

Arrhythmias

Seizures

Metabolic acidosis

Coma

Question 15

What are the non-neurotransmitter and non-cardiac complications and side effects of tricyclic antidepressants?

Answer 15

Peripheral neuropathy

Gynaecomastia

SIADH

Question 16

What are the ECG changes associated with tricyclic antidepressant overdose?

Answer 16

Sinus tachycardia

Widening of QRS: (more than 100ms is associated with an increased risk of seizures whilst QRS more than 160ms is associated with ventricular arrhythmias)

Prolongation of QT interval

Question 17

How do we manage someone who has taken an overdose of amitriptyline?

Answer 17

IV bicarbonate reduces risk of seizures and arrhythmias in severe toxicity

IV lipid emulsion is increasingly used to bind free drug and reduce toxicity

Question 18

What are the anti-arrhythmics that are contraindicated in the management of TCA overdose?

Answer 18

Class 1a (e.g. Quinidine) and class Ic antiarrhythmics (e.g. Flecainide) are contraindicated as they prolong depolarisation.

Class III drugs such as amiodarone and sotalol should also be avoided as they prolong the QT interval.

Response to lignocaine is variable and it should be emphasized that correction of acidosis is the first line in management of tricyclic induced arrhythmias

Question 19

What is the rare arrhythmia associated with prolonged QT interval?

Answer 19

Torsades de pointes

Question 20

Why is torsades de pointes arrhythmia particularly dangerous?

Answer 20

Deteriorates into VF and hence leads to sudden death

Question 21

How do we treat someone whose rhythm is found to be torsades de pointes on ECG?

Answer 21

IV magnesium sulphate