Regarding the pharmacological properties of antidepressants, all of the following statements are correct EXCEPT:

Explanation

## Pharmacological Mechanisms of Antidepressants ### Monoamine Reuptake Inhibition **Key Point:** The three main classes differ fundamentally in their selectivity for monoamine transporters. | Class | Serotonin | Noradrenaline | Dopamine | Anticholinergic | |-------|-----------|---------------|----------|----------------| | SSRI | ✓✓✓ | ✗ | ✗ | Minimal | | SNRI | ✓✓ | ✓✓ | ± (dose-dependent) | Minimal | | TCA | ✓✓ | ✓✓ | ✗ | ✓✓✓ | ### Why the Correct Answer (Option 4) Is Wrong **High-Yield:** SSRIs and all antidepressants require **2–4 weeks** of continuous treatment to achieve therapeutic benefit, NOT 3–5 days. This delayed onset reflects the time needed for: 1. Downregulation of presynaptic autoreceptors (serotonin 1A receptors) 2. Adaptive changes in postsynaptic receptor sensitivity 3. Gene expression changes in mood-regulating circuits **Clinical Pearl:** In acute suicidal ideation, SSRIs do NOT provide rapid symptom relief. Early suicide risk actually increases in the first 1–2 weeks (black box warning). Management requires: - Close monitoring (weekly visits for first 4 weeks) - Concurrent psychotherapy - Benzodiazepines for acute anxiety (not the SSRI itself) - Hospitalization if high risk **Warning:** Claiming SSRIs work within days is a common trap question designed to test whether students conflate "faster than TCAs" with "fast in absolute terms." SSRIs are marginally faster than TCAs (by ~1 week), but both require weeks. ### Correct Statements (Options 1, 2, 3) - **Option 1 (SSRI selectivity):** Accurate. SSRIs have >100-fold selectivity for serotonin transporters over noradrenaline or dopamine transporters. - **Option 2 (SNRI mechanism):** Accurate. Venlafaxine at doses >225 mg/day shows measurable dopamine reuptake inhibition; duloxetine and desvenlafaxine have minimal dopamine effects. - **Option 3 (TCA anticholinergic effects):** Accurate. TCAs are potent muscarinic antagonists (amitriptyline > imipramine > nortriptyline), causing dry mouth, urinary hesitancy, constipation, tachycardia, and blurred vision. [cite:Harrison 21e Ch 470]