Differentiated effects of the multimodal antidepressant vortioxetine on sleep architecture: Part 1, a pharmacokinetic/pharmacodynamic comparison with paroxetine in healthy men.
Level 2 - randomized trial
Randomized, double-blind, placebo-controlled crossover trial in humans
PubMed 26253622 · doi:10.1177/0269881115599387
What was done
In a randomized, double-blind, four-way crossover, placebo-controlled study, 24 healthy young men received three consecutive days of vortioxetine 20 mg, vortioxetine 40 mg, paroxetine 20 mg, or placebo across four treatment periods separated by at least three weeks. Polysomnography and pharmacokinetic blood sampling were conducted on pre-dose nights and on nights 1 and 3 of dosing. Measured drug plasma concentrations were used to estimate serotonin transporter (SERT) occupancies.
What was found
The abstract reports no exact numerical values or effect sizes. It states that all three active treatments significantly increased REM onset latency and decreased total time spent in REM sleep. Pharmacokinetic/pharmacodynamic analysis identified significant relationships between drug exposure and REM suppression parameters for both agents. However, at equivalent estimated levels of SERT occupancy, the relationship with REM suppression differed significantly between vortioxetine and paroxetine.
Why it matters
This confirms that vortioxetine's multimodal receptor activity produces a pharmacodynamic profile distinct from a selective serotonin reuptake inhibitor (paroxetine) even at matched levels of SERT occupancy.
Limits
The study was small (n = 24) and restricted entirely to healthy young males. Dosing was limited to three days, precluding evaluation of chronic adaptation. The abstract does not provide exact numerical metrics, confidence intervals, or specific statistical values.
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