What are the common indications for tricyclic antidepressants?
As second-line treatment for moderate-to-severe depression where first-line selective serotonin reuptake inhibitors (SSRIs) are ineffective.
As a treatment option for neuropathic pain, although they are not licensed for this indication.
What is the mechanism of action?
Tricyclic antidepressants inhibit neuronal reuptake of 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.
What are the adverse reactions of tricyclic antidepressants?
ECG changes such as QT and QRS elongation
Extrapyramidal side effects (rare)
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 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.
Which illnesses may be worsened by the antimuscarinic effects of tricyclic antidepressants?
People with ▴prostatic hypertrophy or ▴glaucoma, and those prone to ▴constipation, may have their condition worsened by the drugs' antimuscarinic effects.
What are the important drug interactions of tricyclics?
Tricyclic antidepressants should not be given with ✗monoamine oxidase inhibitors as both drug classes increase 5-HT 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.
What are examples?
What are the common doses for amitryptiline?
Neuropathic pain: amitriptyline is used at a much lower dose (e.g. starting dose 10 mg at night) for this indication than for depression (where starting dose is 75 mg daily).
What is common practice when prescribing tricyclics given their high risk side effect profile?
Tricyclic antidepressants are available as tablets and in oral solution. When prescribing for depression, particularly for people who are at risk of suicide, it is good practice to supply a small quantity of medication at a time (e.g. enough for 2 weeks) to reduce the risk of serious overdose.
How long should you wean a patient off tricyclics?
When the time comes to stop treatment, they should reduce the dose slowly over at least 4 weeks