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-YieldNEET PG
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.
