TeacherOfMedicine: Antidepressants, tricyclics and related drugs

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.

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.

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.

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.

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.

TeacherOfMedicine