How SSRIs and SNRIs work
SSRIs (selective serotonin reuptake inhibitors) block serotonin reuptake (a nerve ending taking its transmitter back from the synapse), and SNRIs block reuptake of both serotonin and noradrenaline.
Remember
Blocking reuptake enhances serotonin signalling with SSRIs, and serotonin and noradrenaline signalling with SNRIs; clinical benefit takes several weeks.
Memory aid
a reuptake inhibitor is a jammed vacuum cleaner, so the transmitter stays in the gap for longer
Think of the transporter as a vacuum cleaner that clears the transmitter from the gap; jamming it leaves the transmitter there for longer.
The synapse is the gap between nerve cells. The cell that releases serotonin is the presynaptic neurone. Its serotonin transporter (the protein that takes serotonin back into the nerve ending) normally pulls serotonin out of the gap, ending the signal.
SSRIs block that transporter. Serotonin then stays longer in the gap and acts on the receptors of the next cell, so serotonin signalling is enhanced. Selective means the target is serotonin, with little effect on noradrenaline or dopamine. SSRIs are usually the first drugs tried in depression.
SNRIs (serotonin noradrenaline reuptake inhibitors) block reuptake of both serotonin and noradrenaline. Serotonin and noradrenaline are both monoamines (neurotransmitters built around one amine group), so these drugs are often called monoamine reuptake inhibitors.
In laboratory studies the transporter is blocked rapidly, yet clinical benefit takes several weeks. The mood improvement develops over weeks, so at least four weeks is advised before judging whether a drug has failed. A response to an SSRI also does not prove that low serotonin caused the depression.
Key facts
- SSRIs
- block the presynaptic serotonin transporter, so serotonin stays in the synaptic cleft (the gap between nerve cells).
- SNRIs
- block reuptake of both serotonin and noradrenaline.
- Selective
- SSRIs target serotonin, with little effect on noradrenaline or dopamine.
- Indirect action
- SSRIs do not directly stimulate serotonin receptors; the extra serotonin then acts on its own receptors.
- Timing
- clinical improvement takes weeks, so wait at least four weeks before judging that a drug has failed.
- Cause
- a response to treatment is no proof that a transmitter deficiency caused the depression.
Exam traps
- An SSRI does not act as a direct agonist (a drug that binds to and activates a receptor) at serotonin receptors, because it works indirectly, raising how much serotonin is available.
- Stopping the enzyme monoamine oxidase, which breaks down serotonin and other monoamines, is not how SSRIs work, because that action belongs to monoamine oxidase inhibitors, a separate, older antidepressant class.
- SSRIs do not increase serotonin manufacture, because they work on the transporter that clears serotonin from the synapse.
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