SSRIs and serotonin in anxiety
SSRIs (selective serotonin reuptake inhibitors) can reduce anxiety by blocking the recapture of serotonin, so more of it stays in the synaptic cleft (the tiny gap between two neurones).
Remember
An SSRI blocks reuptake, the taking back up of serotonin, so serotonin stays in the synaptic cleft for longer; the anxiety benefit builds over several weeks.
Memory aid
An SSRI is a plug in the recycling chute
Serotonin that cannot be taken back up stays in the gap and keeps signalling.
A neurotransmitter such as serotonin is released into the synaptic cleft and acts on receptors. Normally the serotonin transporter, a protein on the presynaptic neurone (the sending nerve cell), pulls serotonin back out of the cleft. This recapture is called reuptake.
A selective serotonin reuptake inhibitor blocks that transporter. With the transporter blocked, serotonin stays in the cleft for longer and keeps stimulating the receiving neurone. Serotonin signalling in the limbic system (the group of deep brain structures that handles emotion and fear) therefore rises, and this can reduce anxiety.
Serotonin is one of the two main neurotransmitters that influence anxiety disorders, together with GABA (gamma-aminobutyric acid, the main inhibitory neurotransmitter of the brain: it acts as a natural brake). Benzodiazepines, which enhance GABA, act on a different system, so the drug class tells you the system: SSRIs act on serotonin and benzodiazepines act on GABA. Serotonin-noradrenaline reuptake inhibitors, for example venlafaxine and duloxetine, are a different class from SSRIs: they block the reuptake of noradrenaline as well as serotonin.
The benefit is not immediate. Several weeks of treatment are needed, and in the first days or weeks an SSRI can cause early activation symptoms, for example jitteriness and increased anxiety, which is worth warning patients about.
Key facts
- Mechanism
- SSRIs block the serotonin transporter, so serotonin is not recaptured.
- Effect
- more serotonin stays in the synaptic cleft, increasing signalling in limbic circuits.
- Timing
- the anxiety benefit builds over several weeks, with possible early jitteriness.
- Contrast
- benzodiazepines act on GABA instead of serotonin.
- Main transmitters in anxiety disorders
- serotonin and GABA.
- Different class
- serotonin-noradrenaline reuptake inhibitors, such as venlafaxine and duloxetine, block the reuptake of noradrenaline as well as serotonin, unlike SSRIs.
Exam traps
- SSRIs do not work by raising gamma-aminobutyric acid: benzodiazepines increase GABA transmission, while SSRIs inhibit serotonin reuptake.
- Noradrenaline is not the neurotransmitter SSRIs act on: drugs that block its reuptake as well as serotonin's are a different class.
- Dopamine belongs to a separate transmitter system, and because SSRIs are selective for serotonin reuptake, dopamine is not what they most directly raise.
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