The Effect of Gastric Bypass on the Pharmacokinetics of Serotonin Reuptake Inhibitors

Depression Clinical Trial

Official title:

The Effect of Gastric Bypass on the Pharmacokinetics of Serotonin Reuptake Inhibitors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01317147
• Other study ID #: PRO07120162
• Status: Completed
• Phase: N/A
• First received: March 15, 2011
• Last updated: March 15, 2011
• Start date: August 2007
• Est. completion date: August 2010

Study information

• Verified date: March 2011
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The morbidly obese frequently present with mood and anxiety disorders, which are often treated with serotonin reuptake inhibitors (SRI) antidepressant drugs. The investigators hypothesized that gastric bypass surgery would decrease the absorption of SRI. The investigators also wished to determine whether a reduction in SRI levels would increase the likelihood of worsening depressive symptoms.

Description:

Twelve RYGB candidates who were successfully treated with an SRI for primary mood or anxiety disorders were studied prospectively. Blood samples for SRI plasma levels were drawn immediately after dose for pharmacokinetic studies (PK) preoperatively. Maximum concentration (CMAX), time to CMAX (TMAX), and Area Under Concentration/Time curve (AUC) were determined. PK studies were repeated at one, six, and twelve months post-operatively. PK data were corrected for dose at each study time point. The Structured Interview Guide for the Hamilton Depression Rating Scale— Atypical Depression Symptom Version was used to quantify depressive symptoms.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Able to tolerate general anesthesia

• Able to document prior unsuccessful attempts at weight loss under medical supervision during the last 6 months

• Able to provide informed consent

• Cleared for surgery by primary care MD, dietician, and psychiatrist

• SRI treatment specifically for depression for =6 wks at constant dose for last 2 out of 6 wks

Exclusion Criteria:

• pregnancy

• Unwilling or unable to comply with postoperative requirements for diet, supplements, exercise, or followup

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Anxiety Disorder
• Anxiety Disorders
• Depression
• Gastric Bypass

Intervention

Procedure:
• Roux-en-Y gastric bypass (RYGBP)

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pittsburgh	American Society for Metabolic and Bariatric Surgery

Country where clinical trial is conducted

United States, 

References & Publications (31)

Adams TD, Gress RE, Smith SC, Halverson RC, Simper SC, Rosamond WD, Lamonte MJ, Stroup AM, Hunt SC. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007 Aug 23;357(8):753-61. — View Citation

Alciati A, D'Ambrosio A, Foschi D, Corsi F, Mellado C, Angst J. Bipolar spectrum disorders in severely obese patients seeking surgical treatment. J Affect Disord. 2007 Aug;101(1-3):131-8. Epub 2007 Jan 16. — View Citation

Ali MR, Rasmussen JJ, Monash JB, Fuller WD. Depression is associated with increased severity of co-morbidities in bariatric surgical candidates. Surg Obes Relat Dis. 2009 Sep-Oct;5(5):559-64. doi: 10.1016/j.soard.2008.10.015. Epub 2008 Nov 21. — View Citation

Behrns KE, Smith CD, Sarr MG. Prospective evaluation of gastric acid secretion and cobalamin absorption following gastric bypass for clinically severe obesity. Dig Dis Sci. 1994 Feb;39(2):315-20. — View Citation

Bodnar LM, Wisner KL. Nutrition and depression: implications for improving mental health among childbearing-aged women. Biol Psychiatry. 2005 Nov 1;58(9):679-85. Epub 2005 Jul 25. Review. — View Citation

Brandacher G, Winkler C, Aigner F, Schwelberger H, Schroecksnadel K, Margreiter R, Fuchs D, Weiss HG. Bariatric surgery cannot prevent tryptophan depletion due to chronic immune activation in morbidly obese patients. Obes Surg. 2006 May;16(5):541-8. — View Citation

Brolin RE. Update: NIH consensus conference. Gastrointestinal surgery for severe obesity. Nutrition. 1996 Jun;12(6):403-4. Review. — View Citation

Clark MM, Niaura R, King TK, Pera V. Depression, smoking, activity level, and health status: pretreatment predictors of attrition in obesity treatment. Addict Behav. 1996 Jul-Aug;21(4):509-13. — View Citation

First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical interview for DSM-IV axis I disorders—patient edition. : New York State Psychiatric Institute; 1996.

Gubbins PO, Bertch KE. Drug absorption in gastrointestinal disease and surgery. Clinical pharmacokinetic and therapeutic implications. Clin Pharmacokinet. 1991 Dec;21(6):431-47. Review. — View Citation

Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49(2):71-87. doi: 10.2165/11318100-000000000-00000. Review. — View Citation

Kinzl JF, Schrattenecker M, Traweger C, Mattesich M, Fiala M, Biebl W. Psychosocial predictors of weight loss after bariatric surgery. Obes Surg. 2006 Dec;16(12):1609-14. — View Citation

Legenbauer T, De Zwaan M, Benecke A, Muhlhans B, Petrak F, Herpertz S. Depression and anxiety: their predictive function for weight loss in obese individuals. Obes Facts. 2009;2(4):227-34. doi: 10.1159/000226278. Epub 2009 Aug 17. — View Citation

Magee SR, Shih G, Hume A. Malabsorption of oral antibiotics in pregnancy after gastric bypass surgery. J Am Board Fam Med. 2007 May-Jun;20(3):310-3. — View Citation

Malinowski SS. Nutritional and metabolic complications of bariatric surgery. Am J Med Sci. 2006 Apr;331(4):219-25. Review. — View Citation

Miller AD, Smith KM. Medication and nutrient administration considerations after bariatric surgery. Am J Health Syst Pharm. 2006 Oct 1;63(19):1852-7. Review. — View Citation

Onyike CU, Crum RM, Lee HB, Lyketsos CG, Eaton WW. Is obesity associated with major depression? Results from the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 2003 Dec 15;158(12):1139-47. — View Citation

Padwal R, Brocks D, Sharma AM. A systematic review of drug absorption following bariatric surgery and its theoretical implications. Obes Rev. 2010 Jan;11(1):41-50. doi: 10.1111/j.1467-789X.2009.00614.x. Epub 2009 Jun 2. Review. — View Citation

Pihlajamäki J, Grönlund S, Simonen M, Käkelä P, Moilanen L, Pääkkönen M, Pirinen E, Kolehmainen M, Kärjä V, Kainulainen S, Uusitupa M, Alhava E, Miettinen TA, Gylling H. Cholesterol absorption decreases after Roux-en-Y gastric bypass but not after gastric banding. Metabolism. 2010 Jun;59(6):866-72. doi: 10.1016/j.metabol.2009.10.004. Epub 2009 Dec 16. — View Citation

Reis M, Aberg-Wistedt A, Agren H, Akerblad AC, Bengtsson F. Compliance with SSRI medication during 6 months of treatment for major depression: an evaluation by determination of repeated serum drug concentrations. J Affect Disord. 2004 Nov 1;82(3):443-6. — View Citation

Roerig JL, Steffen K, Zimmerman C, Mitchell JE, Crosby RD, Cao L. Preliminary comparison of sertraline levels in postbariatric surgery patients versus matched nonsurgical cohort. Surg Obes Relat Dis. 2012 Jan-Feb;8(1):62-6. doi: 10.1016/j.soard.2010.12.003. Epub 2010 Dec 15. — View Citation

Rusch MD, Andris D. Maladaptive eating patterns after weight-loss surgery. Nutr Clin Pract. 2007 Feb;22(1):41-9. Review. — View Citation

Ruz M, Carrasco F, Rojas P, Codoceo J, Inostroza J, Rebolledo A, Basfi-fer K, Csendes A, Papapietro K, Pizarro F, Olivares M, Sian L, Westcott JL, Hambidge KM, Krebs NF. Iron absorption and iron status are reduced after Roux-en-Y gastric bypass. Am J Clin Nutr. 2009 Sep;90(3):527-32. doi: 10.3945/ajcn.2009.27699. Epub 2009 Jul 22. — View Citation

Sanchez-Santos R, Del Barrio MJ, Gonzalez C, Madico C, Terrado I, Gordillo ML, Pujol J, Moreno P, Masdevall C. Long-term health-related quality of life following gastric bypass: influence of depression. Obes Surg. 2006 May;16(5):580-5. — View Citation

Sarwer DB, Cohn NI, Gibbons LM, Magee L, Crerand CE, Raper SE, Rosato EF, Williams NN, Wadden TA. Psychiatric diagnoses and psychiatric treatment among bariatric surgery candidates. Obes Surg. 2004 Oct;14(9):1148-56. — View Citation

Schauer PR, Ikramuddin S, Gourash W, Ramanathan R, Luketich J. Outcomes after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Ann Surg. 2000 Oct;232(4):515-29. — View Citation

Seaman JS, Bowers SP, Dixon P, Schindler L. Dissolution of common psychiatric medications in a Roux-en-Y gastric bypass model. Psychosomatics. 2005 May-Jun;46(3):250-3. — View Citation

Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry. 2010 Oct;71(10):1259-72. doi: 10.4088/JCP.09r05346blu. Review. — View Citation

Skottheim IB, Stormark K, Christensen H, Jakobsen GS, Hjelmesaeth J, Jenssen T, Reubsaet JL, Sandbu R, Asberg A. Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients. Clin Pharmacol Ther. 2009 Sep;86(3):311-8. doi: 10.1038/clpt.2009.82. Epub 2009 Jun 3. — View Citation

Williams JBW, Terman M. Structured Interview Guide for the Hamilton Depression Rating Scale with Ayptical Depression Supplement (SIGH-ADS). New York: New York State Psychiatric Institute; 2003.

Wills SM, Zekman R, Bestul D, Kuwajerwala N, Decker D. Tamoxifen malabsorption after Roux-en-Y gastric bypass surgery: case series and review of the literature. Pharmacotherapy. 2010 Feb;30(2):217. doi: 10.1592/phco.30.2.217. Review. — View Citation

* Note: There are 31 references in all — Click here to view all references