Evidence-Based Reviews

Bariatric procedures: Managing patients after surgery

Current Psychiatry. 2011 January;10(1):19-A

References

1. Mechanick JI, Kushner RF, Sugerman HJ, et al. American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic and Bariatric Surgery Medical guidelines for clinical practice for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient. Endocr Pract. 2008;14:318-336.

2. NIH conference. Gastrointestinal surgery for severe obesity. Consensus Development Conference Panel. Ann Intern Med. 1991;115:956-961.

3. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292:1724-1737.

4. Maggard MA, Shugarman LR, Suttorp M, et al. Meta-analysis: surgical treatment of obesity. Ann Intern Med. 2005;142:547-559.

5. Hodo DM, Waller JL, Martindale RG, et al. Medication use after bariatric surgery in a managed care cohort. Surg Obes Rel Dis. 2008;4:601-607.

6. Sarwer DB, Wadden TA, Fabricatore AN. Psychosocial and behavioral aspects of bariatric surgery. Obes Res. 2005;13:639-648.

7. Mitchell JE, de Zwaan M. Bariatric surgery: a guide for mental health professionals. New York, NY: Routledge; 2005.

8. Malone M, Alger-Mayer SA. Medication use patterns after gastric bypass surgery for weight management. Ann Pharmacopher. 2005;39:637-642.

9. Buchwald H. and the Consensus Conference Panel. Consensus conference statement: bariatric surgery for morbid obesity: health implications for patients, health professionals, and third-party payers. Surg Obes Rel Dis. 2005;1:371-381.

10. Needleman BJ, Happel LC. Bariatric surgery: choosing the optimal procedure. Surg Clin North Am. 2008;88:991-1007.

11. Albrecht RJ, Pories WJ. Surgical intervention for the severely obese. Baillieres Best Pract Res Clin Endocrinol Metab. 1999;13:149-172.

12. Brolin RE. Bariatric surgery and long-term control of morbid obesity. JAMA. 2002;288:2793-2796.

13. Santry HP, Gillen DL, Lauderdale DS. Trends in bariatric surgical procedures. JAMA. 2005;294:1909-1917.

14. Brolin RE, Kenler HA, Gorman RC, et al. The dilemma of outcome assessment after operations for morbid obesity. Surgery. 1989;105:337-346.

15. Sjöström L, Lindroos AK, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004;351:2683-2693.

16. Sjöström L, Narbro K, Sjöström CD, et al. and the Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357:741-752.

17. Bocchieri LE, Meana M, Fisher BL. A review of psychosocial outcomes of surgery for morbid obesity. J Psychosom Res. 2002;52:155-165.

18. Herpertz S, Kielmann R, Wolf AM, et al. Do psychosocial variables predict weight loss or mental health after obesity surgery? A systematic review. Obes Res. 2004;12:1554-1569.

19. Kalarchian MA, Marcus MD, Levine MD, et al. Psychiatric disorders among bariatric surgery candidates: relationship to obesity and functional health status. Am J Psychiatry. 2007;164:328-334.

20. Rosenberger PH, Henderson KE, Grilo CM. Psychiatric disorder comorbidity and association with eating disorders in bariatric surgery patients: a cross-sectional study using structured interview based diagnosis. J Clin Psychiatry. 2006;67:1080-1085.

21. Kalarchian MA, Marcus MD, Levine MD, et al. Relationship of psychiatric disorders to 6-month outcomes after gastric bypass. Surg Obes Relat Dis. 2008;4:544-549.

22. Rutledge T, Groesz LM, Savu M. Psychiatric factors and weight loss patterns following gastric bypass surgery in a veteran population. Obes Surg. 2009;[Epub ahead of print].

23. Kinzl JF, Schrattenecker M, Traweger C, et al. Psychosocial predictors of weight loss after bariatric surgery. Obes Surg. 2006;16:1609-1614.

24. Bauchowitz AU, Gonder-Frederick LA, Olbrisch ME, et al. Psychosocial evaluation of bariatric surgery candidates: a survey of present practices. Psychosom Med. 2005;67(5):825-832.

25. Wadden TA, Sarwer DB, Womble LG, et al. Psychosocial aspects of obesity and obesity surgery. Surg Clin North Am. 2001;81:1001-1024.

26. Fabricatore AN, Crerand CE, Wadden TA, et al. How do mental health professionals evaluate candidates for bariatric surgery? Survey results. Obes Surg. 2006;16:567-573.

27. Sarwer DB, Cohn NI, Gibbons LM, et al. Psychiatric diagnoses and psychiatric treatment among bariatric surgery candidates. Obes Surg. 2004;14(9):1148-1156.

28. Larsen JK, Greenen R, van Ramshorst B, et al. Psychosocial functioning before and after laparoscopic adjustable gastric banding: a cross-sectional study. Obes Surg. 2003;13(4):629-636.

29. Clark MM, Balsiger BM, Sletten CD, et al. Psychosocial factors and 2-year outcome following bariatric surgery for weight loss. Obes Surg. 2003;13(5):739-745.

30. Padwal R, Brocks D, Sharma AM. A systematic review of drug absorption following bariatric surgery and its theoretical implications. Obes Rev. 2010;11(1):41-50.

31. Macgreggor AMC, Boggs L. Drug distribution in obesity and following bariatric surgery: a literature review. Obes Surg. 1996;6:17-27.

32. Malone M. Altered drug disposition in obesity and after bariatric surgery. Nutr Clin Pract. 2003;18:131-135.

33. Miller AD, Smith KM. Medication and nutrient administration considerations after bariatric surgery. Am J Health Syst Pharm. 2006;63:1852-1857.

34. Paine MF, Khalighi M, Fisher JM, et al. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Pharmacol Exp Ther. 1997;283:1552-1562.

35. Skottheim IB, Stormark K, Christensen H, et al. Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients. Clin Pharmacol Ther. 2009;86(3):311-318.

36. Hamad GG, Kozak GM, Wisner KL, et al. The effect of gastric bypass on SSRI pharmacokinetics and pharmacodynamics. Abstract presented at: American Society for Metabolic and Bariatric Surgery 25 Annual Meeting; June 15-20, 2008; Washington, DC.

37. Seaman JS, Bowers SP, Dixon P, et al. Dissolution of common psychiatric medications in a Roux-en-Y gastric bypass model. Psychosomatics. 2005;46:250-253.

medication absorption from the GI tract into systemic circulation
distribution throughout the body as fat mass and total body water change after surgery
drug metabolism.

Clinical Point

The effects of bariatric surgery on medication pharmacokinetic parameters appears to be drug-specific

The effects of bariatric surgery on medication PK appears to be drug-specific.^30-33

The bypassed portion of the GI tract is the primary absorption site for most medications; therefore, the length of the Roux limb may affect the extent of drug absorption impairment. However, the duodenum wall is one of many locations of the cytochrome P450 (CYP) isoenzymes CYP3A4 and CYP3A5,³⁴ which are the primary metabolic enzymes for drugs such as atorvastatin. Eliminating this portion of the bowel could increase rather than decrease bioavailability.³⁵ Alterations in drug absorption also may result from changes in gastric emptying rate, reduced exposure to absorptive mucosal surfaces, and alterations in gastric pH that can impair drug dissolution and solubility.³⁰ These changes could reduce medication bioavailability.³³ The impact of such changes may differ according to the characteristics of the specific drug. It has been theorized that drugs that are intrinsically poorly absorbed, are highly lipophilic, and undergo enterohepatic circulation carry the highest risk of malabsorption.³⁰ Antidepressants vary in the extent to which they demonstrate these characteristics. Progressive changes in the volume of distribution as weight is lost also could affect the blood levels of some antidepressants.

A series of small studies and case reports of PK changes in medications such as digoxin, oral contraceptives, cyclosporine, sulfisoxazole, and tacrolimus after jejunoileal bypass—an older, obsolete bariatric procedure—reveal variability in the surgery’s effect on PK parameters, although most reported reduced absorption. Data specific to RYGB consist of small studies and case series that show reduced absorption after surgery with significant variability among agents (see our bibliography of studies describing PK changes in nonpsychiatric medications after bariatric surgery). In a systematic literature review, Padwal et al found evidence for a decreased magnitude of absorption in 15 of 22 studies of jejunoileal bypass patients, 1 of 3 studies of gastric bypass/gastroplasty, and no studies examining biliopancreatic diversion.³⁰

It is unclear if antidepressant absorption is impaired after RYGB because currently only 1 case report presents in-vivo data. Hamad et al describe an obese patient (BMI 46 kg/m²) taking sertraline, 100 mg/d, for depression.³⁶ Researchers measured sertraline levels before and 1 month after RYGB, at which time the patient’s depression worsened. After surgery, sertraline maximum concentration was lower (14.4 ng/ml vs 41.6 ng/ml), trough concentration was lower (11.1 ng/ml vs 17.5 ng/ml), and time to maximum concentration was shorter (240 vs 300 minutes). This suggests that a shift in sertraline absorption after surgery may have contributed to the patient’s worsened mood symptoms.

Clinical Point

There may be significant variability among antidepressants with regard to implications of an altered GI environment

An in-vitro study that simulated preand post-RYGB GI environments found that 12 of 22 psychotropic drugs tested dissolved differently between the models.³⁷ Whereas the dissolved fractions of amitriptyline, fluoxetine, paroxetine, and sertraline were significantly less in the post-RYGB environment, bupropion dissolved to a greater extent in the pre-RYGB environment, and venlafaxine and citalopram were not different between the 2 conditions (Table).³⁷ Although several limitations prevent translating these data into clinical recommendations, this study suggests that there may be significant variability among medications with regard to the implications of an altered GI environment.

Bibliography

PK changes in nonpsychiatric medications after bariatric surgery

Blouin RA, Bauer LA, Miller DD, et al. Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrob Agents Chemother. 1982;21(4):575-580.

Blouin RA, Brouwer KL, Record KE, et al. Amikacin pharmacokinetics in morbidly obese patients undergoing gastric-bypass surgery. Clin Pharm. 1985;4:70-72.

Chenhsu RY, Wu Y, Katz D, et al. Dose-adjusted cyclosporine c2 in a patient with jejunoileal bypass as compared to seven other liver transplant recipients. Ther Drug Monit. 2003;25(6):665-670.

Fuller AK, Tingle D, DeVane CL, et al. Haloperidol pharmacokinetics following gastric bypass surgery. J Clin Psychopharmacol. 1986;6:376-378.

Garrett ER, Süverkrup RS, Eberst K, et al. Surgically affected sulfisoxazole pharmacokinetics in the morbidly obese. Biopharm Drug Dispos. 1981;2:329-365.

Gerson CD, Lowe EH, Lindenbaum J. Bioavailability of digoxin tablets in patients with gastrointestinal dysfunction. Am J Med. 1980;69:43-49.

Hamad GG, Kozak GM, Wisner KL, et al. The effect of gastric bypass on SSRI pharmacokinetics and pharmacodynamics. Abstract presented at: American Society for Metabolic and Bariatric Surgery 25th Annual Meeting; June 15-20, 2008; Washington, DC.

Kelley M, Jain A, Kashyap R, et al. Change in oral absorption of tacrolimus in a liver transplant recipient after reversal of jejunoileal bypass: case report. Transplant Proc. 2005; 37:3165-3167.

Knight GC, Macris MP, Peric M, et al. Cyclosporine A pharmacokinetics in a cardiac allograft recipient with a jejunoileal bypass. Transplant Proc. 1988;20:351-355.

Marcus FI, Quinn EJ, Horton H, et al. The effect of jejunoileal bypass on the pharmacokinetics of digoxin in man. Circulation. 1977;55:537-541.

Magee SR, Shih G, Hume A. Malabsorption of oral antibiotics in pregnancy after gastric bypass surgery. J Am Board Fam Med. 2007;20:310-313.

Marterre WF, Hariharan S, First MR, et al. Gastric bypass in morbidly obese kidney transplant recipients. Clin Transplant. 1996;10:414-419.

Prince RA, Pincheira JC, Mason EE, et al. Influence of bariatric surgery on erythromycin absorption. J Clin Pharmacol. 1984;24:523-527.

Rogers CC, Alloway RR, Alexander JW, et al. Pharmacokinetics of mycophenolic acid, tacrolimus and sirolimus after gastric bypass surgery in end-stage renal disease and transplant patients: a pilot study. Clin Transplant. 2008;22:281-291.

Shepherd MF, Rosborough TK, Schwartz ML. Heparin thrombophylaxis in gastric bypass surgery. Obes Surg. 2003;13(2):249-253.

Skottheim IB, Stormark K, Christensen H, et al. Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients. Clin Pharmacol Ther. 2009;86(3):311-318.

Victor A, Odlind V, Kral JG. Oral contraceptive absorption and sex hormone binding globulins in obese women: effects of jejunoileal bypass. Gastroenterol Clin North Am. 1987;16(3):483-491.

PK: pharmacokinetic