@Mental_Elf @sameerjauhar @ReadReadj @suzypuss @And_Cipriani @ParianteSPILab @jf_moore @CEP_UK @tony_kendrick @wendyburn 1/We are hoping a more pharmacologically informed approach to tapering will help more patients avoid withdrawal effects. Studies which taper people over months and down to tiny fractions of therapeutic doses have already shown success at avoiding withdrawal symptoms
@Mental_Elf @sameerjauhar @ReadReadj @suzypuss @And_Cipriani @ParianteSPILab @jf_moore @CEP_UK @tony_kendrick @wendyburn 2/This makes a lot of sense because the relationship between dose and serotonin transporter occupancy inhibition is hyperbolic (like it is for most drugs). This means very small doses have very significant effects. Halving the dose does not half the effect at receptor targets.
@Mental_Elf @sameerjauhar @ReadReadj @suzypuss @And_Cipriani @ParianteSPILab @jf_moore @CEP_UK @tony_kendrick @wendyburn 3/Rather surprisingly, even one-eighth of the minimum dose still has about half the effect of a therapeutic dose. We therefore advocate for tapering that follows this relationship. In practice, this will mean halving the medication several times, down to very low levels
@Mental_Elf @sameerjauhar @ReadReadj @suzypuss @And_Cipriani @ParianteSPILab @jf_moore @CEP_UK @tony_kendrick @wendyburn 4/This may involve going down to doses as low as one-fortieth of a therapeutic dose. Of course, some patients have no trouble. So we advocate an individualised process that takes this into account. This might involve a test reduction to check people's toleration/sensitivity
@Mental_Elf @sameerjauhar @ReadReadj @suzypuss @And_Cipriani @ParianteSPILab @jf_moore @CEP_UK @tony_kendrick @wendyburn 5/ We think this approach should be subjected to randomised controlled trials to verify. The same rationale has been applied successfully to benzodiazepines - that is, following their hyperbolic pattern of dose-response.
@Mental_Elf @sameerjauhar @ReadReadj @suzypuss @And_Cipriani @ParianteSPILab @jf_moore @CEP_UK @tony_kendrick @wendyburn 6/One graph from the PET study showing the relationship between dose of citalopram and serotonin transporter inhibition with a few lines drawn on should make it fairly clear that linear tapering produces hyperbolic changes, while hyperbolic tapering produces linear changes. 
