Tricyclic antidepressants

Question 1

Example of a Tricyclic antidepressants

Answer 1

Amitriptyline

Question 2

How do Tricyclic antidepressants work?

Answer 2

Tricyclic antidepressants inhibit neuronal reuptake of serotonin (5-HT) and noradrenaline from the synaptic cleft, thereby increasing their availability for neurotransmission. This appears to be the mechanism by which they improve mood and physical symptoms in moderate-to-severe (but not mild) depression and probably accounts for their effect in modifying neuropathic pain.

Tricyclic antidepressants also block a wide array of receptors, including muscarinic, histamine (H1), α-adrenergic (α1 and α2) and dopamine (D2) receptors. This accounts for the extensive adverse effects profile that limits their clinical utility.

Question 3

Indications for Tricyclic antidepressants

Answer 3

As second-line treatment for moderate-to-severe depression where first-line serotonin-specific reuptake inhibitors (SSRIs) are ineffective.

As a treatment option for neuropathic pain, although they are not licensed for this indication.

Question 4

Contraindications for Tricyclic antidepressants

Answer 4

Tricyclic antidepressants should be used with caution in people who are particularly at risk of adverse effects. These include the elderly, people with cardiovascular disease or epilepsy, and people with constipation, prostatic hypertrophy or raised intraocular pressure, which may be worsened by antimuscarinic effects.

Question 5

Side effects for Tricyclic antidepressants

Answer 5

Blockade of antimuscarinic receptors causes dry mouth, constipation, urinary retention and blurred vision. Blockade of H1 and α1 receptors causes sedation and hypotension.

Cardiac adverse effects (multiple mechanisms) include arrhythmias and ECG changes (including prolongation of the QT and QRS durations). In the brain, more serious effects include convulsions, hallucinations and mania. Blockade of dopamine receptors can cause breast changes and sexual dysfunction and rarely causes extrapyramidal symptoms (tremor and dyskinesia).

Tricyclic antidepressants are extremely dangerous in overdose, causing severe hypotension, arrhythmias, convulsions, coma and respiratory failure, which can be fatal.

Sudden withdrawal of tricyclic antidepressants can cause gastrointestinal upset, neurological and influenza-like symptoms and sleep disturbance.

Question 6

Interactions of Tricyclic antidepressants

Answer 6

Tricyclic antidepressants should not be given with monoamine oxidase inhibitors as both drug classes increase serotonin and noradrenaline levels at the synapse and together they can precipitate hypertension and hyperthermia or serotonin syndrome (see Antidepressants, selective serotonin reuptake inhibitors). Tricyclic antidepressants can augment antimuscarinic, sedative or hypotensive adverse effects of other drugs.

Question 7

Elimination of Tricyclic antidepressants

Answer 7

Renal

Question 8

Patient information on Tricyclic antidepressants

Answer 8

Tricyclic antidepressants are available as tablets and in oral solution.

Advise patients that treatment will improve symptoms over a few weeks, particularly sleep and appetite. Discuss referring them for psychological therapy, which may offer more long-term benefits than drug treatment. Explain that they should carry on with drug treatment for at least 6 months after they feel better to stop the depression from coming back (2 years for recurrent depression). Warn them not to stop treatment suddenly as this may cause flu-like withdrawal symptoms and sleeplessness. When the time comes to stop treatment, they should reduce the dose slowly over 4 weeks. While patients may find some of the more common side effects unpleasant, they may tolerate them in favour of relieving depressive symptoms. Discussing at an early stage what side effects are expected may encourage patients to persist with treatment; at least until the full antidepressant effects are realised.