How do SSRIs work in detail?
We know that too little serotonin activity in the brain can cause the symptoms many conditions e.g. depression, general anxiety, social anxiety, obsessive thoughts, post-traumatic stress disorder, panic, pre-menstrual syndrome and agoraphobia. If this is true, then boosting serotonin these should help to reduce the symptoms. One way of doing this is to block the reuptake (recycling) of transmitter. This is just what an SSRI (e.g. escitalopram, citalopram, fluoxetine, paroxetine, sertraline) does. An SSRI is a Selective Serotonin Reuptake Inhibitor and blocks the reuptake of serotonin. So, the next time an impulse comes along, there is more transmitter, a stronger message is passed, and activity in that part of the brain is increased.
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1. A brain cell decides to send a message to another cell. |
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2. The electrical impulse is sent from the brain cell down one of the nerve fibres. |
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3. This message arrives and the transmitter is released. But an SSRI is also hanging around. |
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4. The transmitters hit the receptor on the other side. |
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5. The message that is passed is definitely less effective, causing the symptoms you are getting e.g. low mood. |
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6. The transmitter is either broken or recycled. However, the SSRI blocks the reuptake of serotonin back into the nerve ending. Although a bit extra may be broken down by the enzyme, the end result is that there is some transmitter hanging around in the gap (synaptic cleft). Not enough to trigger another message though. |
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The next impulse comes down the nerve fibre. |
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As it arrives, transmitter is released as usual. |
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However, the amount that is released adds to the lot that is still hanging around from the last message or impulse. |
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The net result is that the message passed is either stronger or more easily passed than the previous one. So, if lack of messages or not strong enough messages causes a drop in mood or other symptoms, boosting these messages will help correct this, raising mood. |
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The important thing to remember is that SSRI antidepressants probably mainly work by correcting the effect of having too little transmitter. They are NOT STIMULANTS. They have a much more specific way of working than stimulating you.
As the author of this once saw painted on the end of a building “depression is a defect in chemicals not character”.
As we’ve just seen, SSRIs mainly block the reuptake of just serotonin. This is why they are called the SSRIs ie. Selective Serotonin Reuptake Inhibitors. Too much serotonin in some other parts of the brain can make you feel sick, less hungry and get headaches or migraines.
In much the same way as antidepressants take a week or so to start working, most of the side effects tend to wear off over a week or so as the brain gets used to them. Starting at a lower dose for a few days also helps.
Similarly, taking a medicine away from the brain quickly is a bit unfair to it. So, if you are stopping, it is best to reduce the dose for a week or so if you can before stopping to allow the brain to get used to it. As someone once said to me, it’s a bit like stopping a car quickly without your seatbelt on. You can do it, but it hurts. It’s better to slow down gently. Wise words indeed.
So, this is how we think SSRIs work as antidepressants. It is not quite as simple as this, but this is what we currently think is the main way in which they work.