## SSRI Mechanism of Action in MDD ### Correct Mechanisms of SSRIs **Key Point:** SSRIs work through selective inhibition of the serotonin reuptake transporter (SERT), not through monoamine oxidase inhibition. The three correct mechanisms are: 1. **Acute reuptake inhibition** — SSRIs block SERT at the presynaptic terminal, increasing synaptic serotonin concentration within hours. This is the primary acute pharmacological effect. 2. **Receptor desensitization** — Over days to weeks, postsynaptic 5-HT1A and 5-HT1B autoreceptors downregulate, enhancing downstream signal transduction and contributing to the delayed therapeutic effect (2–4 weeks latency). 3. **Neuroplasticity and BDNF** — Chronic SSRI use increases brain-derived neurotrophic factor (BDNF) expression in the hippocampus and prefrontal cortex, promoting neurogenesis and synaptic remodeling. This correlates with the delayed onset of symptom improvement. ### Why Monoamine Oxidase Inhibition is NOT an SSRI Mechanism **High-Yield:** SSRIs do NOT inhibit monoamine oxidase (MAO). This is a critical distinction: | Property | SSRIs | MAOIs | | --- | --- | --- | | **Primary mechanism** | Reuptake inhibition | MAO-A/B inhibition | | **Onset of action** | 2–4 weeks | 1–2 weeks (but slower than SSRIs) | | **Drug interactions** | Moderate | Severe (tyramine, serotonin syndrome risk) | | **Dietary restrictions** | None | Strict (tyramine-rich foods) | | **First-line status** | Yes | Second-line | **Clinical Pearl:** Confusing SSRIs with MAOIs is a common exam trap. Remember: SSRIs = **reuptake** inhibitors; MAOIs = **enzyme** inhibitors. They are mechanistically distinct drug classes. **Warning:** The question specifically asks what is NOT a recognized mechanism. Monoamine oxidase inhibition is the mechanism of MAOIs (phenelzine, tranylcypromine), not SSRIs.
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