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 Rouxen-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 Rouxen-Y gastric bypass. The authors recommend close psychiatric monitoring after surgery.

Weight and Metabolic Outcomes 12 Years after Gastric Bypass

“…29–31 Potential risk factors for suicide after bariatric surgery included age younger than 35 years 32 ; hormonal changes; persistence of coexisting conditions; preexisting depression and other mood disorders; worsening or lack of improvement in health-related quality of life; social, sexual, and relationship issues; poor body image; and a history of maltreatment during childhood. 33 Furthermore, the reduced bioavailability of some serotonin reuptake inhibitors 1 month after gastric bypass 34 and an association between binge-eating disorder before bariatric surgery and the use of psychiatric-related medications 35 have been reported. Whether the increase in suicides is attributable solely to bariatric surgery itself or whether any large, sustained weight loss would also be associated with an increased risk of suicide is unknown.…”

Effect of a Roux-en-Y Gastric Bypass on the Pharmacokinetics of Oral Morphine Using a Population Approach

“…Clinical studies performed recently have involved a small number of patients or were control-case studies [3][4][5][6][7][8][9][10]. Only one compared drug pharmacokinetics at different times after RYGB [6].…”

“…Clinical studies performed recently have involved a small number of patients or were control-case studies [3][4][5][6][7][8][9][10]. Only one compared drug pharmacokinetics at different times after RYGB [6]. It has been difficult to draw any general conclusion; the effects of some oral drugs remain unchanged or are increased (atorvastatin, moxifloxacin, metformin), while those of others are reduced (selective serotonin reuptake inhibitors), according to the post operative period [3][4][5][6][7][8][9][10].…”

“…Only one compared drug pharmacokinetics at different times after RYGB [6]. It has been difficult to draw any general conclusion; the effects of some oral drugs remain unchanged or are increased (atorvastatin, moxifloxacin, metformin), while those of others are reduced (selective serotonin reuptake inhibitors), according to the post operative period [3][4][5][6][7][8][9][10]. It is therefore necessary to carry out controlled studies on each specific drug of interest to evaluate the specific effect of obesity and of RYGB on the pharmacokinetics of that particular drug.…”

Pharmacokinetic considerations for patients with a history of bariatric surgery

“…Second, until recently, sample sizes of published studies were small and much of the available evidence included old case reports and case series. Results based on such a small number of subjects cannot be generalized as most drugs display interindividual variability that must be considered as well [7]. Third, most pharmacokinetic studies have been performed in parallel patient cohorts consisting of those who had bariatric surgery a few months prior and their controls, often matched based on body mass index, age, and sex [8,9].…”