The effect of gastric bypass on the pharmacokinetics of serotonin reuptake inhibitors

Abstract

Objective: Morbidly obese patients frequently present with mood and anxiety disorders, which are often treated with serotonin reuptake inhibitors (SRIs). Having observed that patients treated with SRIs frequently relapse after Roux-en-Y gastric bypass surgery, the authors sought to assess whether SRI bioavailability is reduced postoperatively.

Method: Twelve gastric bypass candidates treated with an SRI for primary mood or anxiety disorders were studied prospectively. Timed blood samples for SRI plasma levels were drawn for pharmacokinetic studies before surgery and 1, 6, and 12 months afterward. Maximum concentration, time to maximum concentration, and area under the concentration/time curve (AUC) were determined.

Results: In eight of the 12 patients, AUC values 1 month after surgery dropped to an average of 54% (SD=18) of preoperative levels (range=36%-80%); in six of these patients, AUC values returned to baseline levels (or greater) by 6 months. Four patients had an exacerbation of depressive symptoms, which resolved by 12 months in three of them. Three of the four patients had a reduced AUC level at 1 month and either gained weight or failed to lose weight between 6 and 12 months. Normalization of the AUC was associated with improvement in symptom scores.

Conclusions: Patients taking SRIs in this study were at risk for reduced drug bioavailability 1 month after Roux-en-Y gastric bypass. The authors recommend close psychiatric monitoring after surgery.

FIGURE 1. Pharmacokinetic Plots for Serotonin Reuptake Inhibitors in Eight Patients Before and After Roux-en-Y Bariatric Bypass Surgery^a

^a The log₁₀ plots show dose-corrected plasma concentration over time.

FIGURE 2. Dose-Corrected AUC Over Time for Serotonin Reuptake Inhibitors Before and After Roux-en-Y Bariatric Bypass Surgery^a

^a AUC=area under the concentration/time curve; SNRI=serotonin-norepinephrine reuptake inhibitor; SSRI=selective serotonin reuptake inhibitor.