A depressed patient is started on amitriptyline. Which adverse effect profile is MOST characteristic of tricyclic antidepressants compared to SSRIs?

• A Weight loss, insomnia, and sexual dysfunction
• B Hyponatraemia due to SIADH and serotonin syndrome at therapeutic doses
• C Tardive dyskinesia after chronic use
• D Dry mouth, urinary retention, QRS widening in overdose, and orthostatic hypotension ✓

Explanation

TCAs have multiple receptor-blocking actions: muscarinic blockade causes dry mouth, constipation, blurred vision, and urinary retention; α1 blockade causes orthostatic hypotension; H1 blockade causes sedation and weight gain. Their most dangerous property is cardiac sodium channel blockade, which in overdose widens the QRS complex and can cause ventricular arrhythmias and heart block — treated with IV sodium bicarbonate. These effects are not shared by SSRIs.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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