What are tricyclic antidepressants and why are they considered high risk?

Tricyclic antidepressants, or TCAs, such as amitriptyline, nortriptyline, and imipramine block the reuptake of serotonin and norepinephrine while also affecting histamine, acetylcholine, and alpha-adrenergic receptors. This broad receptor activity causes significant side effects including sedation, dry mouth, constipation, urinary retention, blurred vision, orthostatic hypotension, and weight gain. TCAs are high risk because they have a narrow therapeutic index and are lethal in overdose, causing cardiac arrhythmias and seizures.