Why SERT occupancy matters when tapering
SERT (serotonin transporter) occupancy refers to the approximate percentage of serotonin transporters in the brain that are occupied or blocked by an antidepressant.
Think of SERT as a transporter that normally removes serotonin from the space between nerve cells. SSRIs and many SNRIs bind to SERT and inhibit this process. SERT occupancy tells us approximately how much of the transporter is being occupied by the medication.
An important finding from PET/SPECT research is that dose and SERT occupancy are not proportional. The relationship is nonlinear (hyperbolic). This means that reducing a dose by a certain number of milligrams does not necessarily produce the same percentage change in SERT occupancy at different points on the dose range.
For example, according to the model used below:
Sertraline
- 50 mg → ~79% occupancy
- 25 mg → ~73%
- 12.5 mg → ~64%
- 6.25 mg → ~52%
- 3 mg → ~36%
- 1 mg → ~17%
So reducing from 50 mg to 25 mg reduces the dose by 50%, but estimated SERT occupancy falls by only about 6 percentage points. Going from 1 mg to 0, however, represents a much larger change in occupancy.
This is one reason why the lower end of an antidepressant taper can be much more pharmacologically significant than the milligram numbers might suggest.
Estimated SERT Occupancy
Drug | Typical dose | ½ dose | ¼ dose | Lower dose | Very low dose | Extremely low
Paroxetine (Paxil) | 20 mg → 72% | 10 mg → 60% | 5 mg → 45% | 2.5 mg → 30% | 1 mg → 15% | 0.5 mg → 8% |
Sertraline (Zoloft) | 50 mg → 79% | 25 mg → 73% | 12.5 mg → 64% | 6.25 mg → 52% | 3 mg → 36% | 1 mg → 17% |
Citalopram (Celexa) | 20 mg → 76% | 10 mg → 68% | 5 mg → 57% | 2.5 mg → 42% | 1.25 mg → 28% | 0.5 mg → 14% |
Escitalopram (Lexapro) | 10 mg → 62% | 5 mg → 54% | 2.5 mg → 42% | 1.25 mg → 29% | 0.5 mg → 15% | 0.25 mg → 8% |
Fluoxetine (Prozac) | 20 mg → 76% | 10 mg → 68% | 5 mg → 57% | 2.5 mg → 42% | 1.25 mg → 28% | 0.5 mg → 14% |
Venlafaxine (Effexor) | 75 mg → 83% | 37.5 mg → 78% | 18.75 mg → 68% | 9.4 mg → 55% | 4.7 mg → 40% | 2 mg → 22% |
Duloxetine (Cymbalta) | 60 mg → 77% | 30 mg → 71% | 15 mg → 61% | 7.5 mg → 47% | 3.75 mg → 33% | 1 mg → 12% |
Desvenlafaxine (Pristiq) | 50 mg → 79% | 25 mg → 68% | 12.5 mg → 53% | 6.25 mg → 37% | 3.1 mg → 23% | 1.5 mg → 12% |
How were these numbers calculated?
The estimates use the following model:
Estimated SERT occupancy = (Vm × dose) ÷ (K + dose)
The approximate parameters used in the Surviving Antidepressants discussion were:
Drug | Vm | K
Paroxetine | 90 | 5
Sertraline | 85 | 4
Citalopram | 85 | 2.5
Escitalopram | 75 | 2
Fluoxetine | 85 | 2.5
Venlafaxine | 90 | 6
Duloxetine | 85 | 6
Desvenlafaxine | 95 | 10
Important limitations
These percentages should be considered estimates, not measurements of an individual person's brain.
The underlying PET/SPECT research directly measured SERT occupancy at various doses, but many of the very-low-dose values in this chart are extrapolations from a mathematical model. The available studies are relatively small, and there are limited direct measurements at very low doses.
SERT occupancy also does not tell us exactly how much antidepressant effect someone is receiving, how severe withdrawal will be, or how quickly an individual should taper. People can respond very differently to the same dose.
Therefore, this chart should be used primarily to illustrate an important concept:
A small dose in milligrams does not necessarily mean a small pharmacological effect.
This may help explain why some people experience significant symptoms when making reductions at the lower end of a taper.
Tapering decisions should be based primarily on the individual's response and symptoms rather than on a SERT occupancy calculation. 
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