Sorensen et al. (2022). The relationship between dose and serotonin transporter occupancy of antidepressants—a systematic review

[Addax]

The relationship between dose and serotonin transporter occupancy of antidepressants—a systematic review. Sorensen et al. 2022

 

Abstract

Brain imaging techniques enable the visualization of serotonin transporter (SERT) occupancy as a measure of the proportion of SERT blocked by an antidepressant at a given dose. We aimed to systematically review the evidence on the relationship between antidepressant dose and SERT occupancy. We searched PubMed and Embase (last search 20 May 2021) for human in vivo, within-subject PET, or SPECT studies measuring SERT occupancy at any dose of any antidepressant with highly selective radioligands ([11C]-DASB, [123I]-ADAM, and [11C]-MADAM). We summarized and visualized the dose-occupancy relationship for antidepressants across studies, overlaying the plots with a curve based on predicted values of a standard 2-parameter Michaelis–Menten model fitted using the observed data. We included seventeen studies of 10 different SSRIs, SNRIs, and serotonin modulators comprising a total of 294 participants, involving 309 unique occupancy measures. Overall, following the Michaelis–Menten equation, SERT occupancy increased with a higher dose in a hyperbolic relationship, with occupancy increasing rapidly at lower doses and reaching a plateau at approximately 80% at the usual minimum recommended dose. All the studies were small, only a few investigated the same antidepressant, dose, and brain region, and few reported information on factors that may influence SERT occupancy. The hyperbolic dose-occupancy relationship may provide mechanistic insight of relevance to the limited clinical benefit of dose-escalation in antidepressant treatment and the potential emergence of withdrawal symptoms. The evidence is limited by non-transparent reporting, lack of standardized methods, small sample sizes, and short treatment duration. Future studies should standardize the imaging and reporting procedures, measure occupancy at lower antidepressant doses, and investigate the moderators of the dose-occupancy relationship.

 

web page: https://www.nature.com/articles/s41380-021-01285-w

 

PDF: https://www.nature.com/articles/s41380-021-01285-w.pdf

Edited February 3, 2023 by Addax
Improper capitalization

[arbor]

Thank you @Addax

[j1290]

Fascinating reading, @Addax  Thank you for posting this!  

I'm no expert so I won't post my conclusion after reading this, but if I understand correctly, this study more or less reflects my own experience.

[Addax]

Glad to hear you both found it a valuable read. It’s of particular interest to me at this point in my taper. I just wish it (or any article) could tell me exactly what to expect.

 

@j1290, You don’t need to be an expert to share what you concluded. Sometimes it’s the “non-experts” who put things in a way that more people connect with and can understand.  So I hope you change your mind and share your thoughts.