tricyclics

Tricyclics, or tricyclic antidepressants (TCAs), are an older class of antidepressant medications named for their characteristic three-ring chemical structure. They were among the first effective treatments for major depressive disorder and have since found roles in other conditions, though they are less commonly used as first-line therapy today due to safety concerns and tolerability.

Mechanism of action centers on inhibition of norepinephrine and serotonin reuptake, primarily by blocking the NET and SERT transporters. In addition, TCAs variably antagonize receptors such as muscarinic cholinergic, histamine H1, and alpha-1 adrenergic receptors. This receptor profile contributes to both therapeutic effects and the notable anticholinergic, sedative, and cardiovascular adverse effects.

Indications and use have evolved. TCAs remain option for treatment-resistant depression and certain chronic pain syndromes, including neuropathic pain, and for migraine prophylaxis. Clomipramine is particularly effective for obsessive-compulsive disorder. They are generally not chosen as first-line antidepressants because of safety concerns, especially in overdose, and because newer agents often have more favorable side-effect profiles.

Common agents include amitriptyline, imipramine, nortriptyline, desipramine, clomipramine, doxepin, amoxapine, and maprotiline. They are categorized as tertiary amines (for example, amitriptyline, imipramine) with stronger anticholinergic and sedative effects, and secondary amines (nortriptyline, desipramine) with somewhat different tolerability. Metabolism is hepatic and varies with age and genetics.

Safety considerations are central. Adverse effects include dry mouth, constipation, blurred vision, urinary retention, drowsiness, weight gain, and orthostatic hypotension. Cardiac conduction abnormalities and arrhythmias in overdose are major risks. TCAs interact with alcohol, other CNS depressants, and monoamine oxidase inhibitors, requiring careful dosing and monitoring. Discontinuation should be gradual.