Bioavailability of Vortioxetine After a Roux-en-Y Gastric Bypass
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LETTER TO THE EDITOR
Bioavailability of Vortioxetine After a Roux-en-Y Gastric Bypass Frederik Vandenberghe 1
&
Patricia Gilet 2 & Youssef Daali 3 & Lucie Favre 2 & Chin B Eap 1,4,5,6
Received: 24 August 2020 / Revised: 7 October 2020 / Accepted: 7 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
The impact of bariatric surgery on depression appears to be positive during the early months (the so-called honeymoon period), but depressive symptoms tend to increase 36 months post-intervention [1]. Despite the high prevalence of depression and obesity, little is known about pharmacokinetic modification of psychotropic drugs in patients undergoing bariatric surgery. Briefly, the reduction of gastric volume leads to a decrease in gastric mixing, an increase in gastric pH, and an increase in gastric emptying, affecting disintegration and dissolution of the oral medication. The reduction in intestine length after Roux-en-Y gastric bypass (RYGB) leads to a reduction in the absorptive surface area and modification of presystemic drug metabolism [2]. Limited clinical data are available for psychotropic drugs and concern mostly antidepressants. Two single-dose cross-sectional pharmacokinetic studies with 100 mg of sertraline and 60 mg of duloxetine found a significant decrease in the area under the plasma concentration time curve compared to the placebo group [3, 4]. A case series of four patients found a 33% (4–71%) decrease of serum escitalopram concentrations compared to preoperative values 2 weeks after RYGB surgery [5]. Another case series of 12 subjects treated with selective serotonin reuptake inhibitors (SSRI) and serotonin-noradrenaline reuptake inhibitors (SNRI) showed a decreased area under the curve (AUC) between 36 to 80% in eight patients 1 month after RYGB intervention [6].
We present here the case of a 24-year-old Caucasian woman with a history of class III obesity, type 2 diabetes, nonalcoholic fatty liver disease, and anxiety-depressive disorder which have previously been unsuccessfully treated with two SSRIs (sertraline and fluoxetine). Vortioxetine, a “multimodal serotonin modulator” acting as an SSRI and additionally on 5HT1A, 5-HT1B, 5-HT3, and 5-HT7 receptors, was introduced with good clinical efficacy on mood symptoms. The latter has a bioavailability of 75%, maximum plasma concentration reached 7–11 h post-dose, and an elimination half-life between 59 and 69 h. It is metabolized extensively in the liver, mainly via cytochrome P450 enzyme (CYP) 2D6 and, to a lesser extent, via CYP3A4, CYP2C19, and CYP2C9 into six inactive metabolites [7]. Additionally, she was treated with metformin (1000 mg/day), liraglutide (1.8 mg/day), and biotin (10 mg/day). Following assessment by the bariatric multidisciplinary team, she was eligible for an RYGB intervention. During the preoperative period, two blood level measurements of vortioxetine at 200 and 126 days before the intervention were taken. All concentrations were determined in steady-state conditions (> 2 weeks at stable dosa
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