Considerations for Psychotropic Medication in Altered GI Patients

1. Considerations for Psychotropic Medication in Patients with Altered Gastrointestinal Physiology Christian Askren, Christopher Fox, Sonja Hutchens, Marjorie Peck

2. Why It Matters: • According to the National Institute of Health (NIH) 35% of the U.S. population remains obese (BMI ≥ 30kg/m2)1. • 20-70% of morbidly obese patients ( BMI ≥ 40 kg/ m2) are also afflicted with a current or past psychiatric disorder.2,3 • As the prevalence of bariatric surgery in patients with psychiatric illnesses increases, it is important to consider changes in absorption and efficacy of medications following GI interventions.4 • Looking at where certain antidepressants, antipsychotics and mood stabilizers are absorbed will allow us to adjust therapy for this population to avoid toxic or sub-therapeutic levels.

4. Short Bowel Syndrome & Roux-en-Y Surgery

5. Methods: How did we go about our research? • Reviewed literature found in PubMed and Embase using Mesh term including: • Anastomosis, Roux-en-y • Bypass, gastric • Short bowel syndrome • Stomach neoplasms • Pyloric stenosis • Mesenteric ischemia • Gastritis, Atrophic • Communication with pharmaceutical manufacturers • In the case that we could not find the product specific properties online we contacted the pharmaceutical manufacturers to question them regarding absorption sites for the medications.

6. Why does this matter? Common mental health conditions in patients undergoing bariatric surgery • depression 19% • binge eating disorder 17% Dawes AJ - JAMA (2016) Mental Health Conditions Among Patients Seeking and Undergoing Bariatric Surgery A Meta-analysis

7. GI Tract

8. SSRI Antidepressants No information on: Paroxetine Duodenum • Citalopram • Fluoxetine • Sertraline Ileum • Fluoxetine • Sertraline

9. No information on: Levomilnacipran SNRI Antidepressants Duodenum • Duloxetine Ileum (low small intestine) • Desvenlafaxine • Venlafaxine

10. SSRIs vs. SNRIs Levels 1-3mo. post-RYGB - Normalization 6-12mo. post-RYGB - Plasma levels unaffected

11. Question: RY is a patient who just had a RYGB one week ago. He has been taking sertraline 50mg for the past 3 years to help manage his depression. He has never tried any other SSRI’s or any SNRI’s. His provider recently read an article detailing changes in drug absorption post-RYGB and asks you what changes you would make to his regimen? Continue sertraline 50mg QD Decrease sertraline dose to 25mg QD Start venlafaxine ER 37.5mg QD and adjust to effective dose, then transition back to sertraline after three months. Discontinue sertraline for three months, then resume 50mg QD

12. Question: RY is a patient who just had a RYGB one week ago. He has been taking sertraline 50mg for the past 3 years to help manage his depression. He has never tried any other SSRI’s or any SNRI’s. His provider recently read an article detailing changes in drug absorption post-RYGB and asks you what changes you would make to his regimen? Continue sertraline 50mg QD Decrease sertraline dose to 25mg QD Start venlafaxine ER 37.5mg QD and adjust to effective dose, then transition back to sertraline after three months. Discontinue sertraline for three months, then resume 50mg QD

13. Tricyclic Antidepressants No information on: • Amitriptyline • Desipramine • Doxepin • Imipramine • Nortriptyline Small intestine • Clomipramine

14. MAOIs No information on: • Phenelzine • Selegiline • Tranylcypromine Small intestine • Isocarboxazid

15. No information on: • Bupropion • Mirtazapine • Vilazodone • Trazodone Other Antidepressants Upper small intestine • Vortioxetine

16. Mood Stabilizers No information on: • Lithium Duodenum • Lamotrigine Upper small intestine • Valproate Lower small intestine • Carbamazepine

17. Question: A 61-year old woman presents to the ED with complaints of lightheadedness, dizziness, weakness and fatigue 12 days post roux-en-Y bypass surgery. Her PMH includes morbid obesity, type 2 diabetes mellitus, nephrogenic diabetes insipidus and bipolar disorder. She had a HR of 48 bpm and a BP of 74/38. She states no changes in her medication but is unable to remember the names of her medications. Which medication do you think is contributing to her symptoms and why? Lithium Carbonate, it has greater dissolution in a post-RYGB environment. Quetiapine, it has less dissolution in a post-RYGB environment. Fluoxetine, it has less dissolution in a post-RYGB environment. No medication is causing her symptoms, she is just seeking attention

18. Question: A 61-year old woman presents to the ED with complaints of lightheadedness, dizziness, weakness and fatigue 12 days post roux-en-Y bypass surgery. Her PMH includes morbid obesity, type 2 diabetes mellitus, nephrogenic diabetes insipidus and bipolar disorder. She had a HR of 48 bpm and a BP of 74/38. She states no changes in her medication but is unable to remember the names of her medications. Which medication do you think is contributing to her symptoms and why? Lithium Carbonate, it has greater dissolution in a post-RYGB environment. Quetiapine, it has less dissolution in a post-RYGB environment. Fluoxetine, it has less dissolution in a post-RYGB environment. No medication is causing her symptoms, she is just seeking attention

19. No information on: • Asenapine • Brexipiprazole • Cariprazine • Chlorpromazine • Clozapine • Fluphenazine • Haloperidol • Loxapine • Lurasidone • Paliperidone • Perphenazine • Quetiapine • Risperidone • Thioridazine • Thiothixene • Trifuoperazine • Ziprasidone Antipsychotics Duodenum • Aripirazole • Iloperidone Small intestine • Olanzapine Colon • Olanzapine

20. Question: A 42 y/o female presents with ongoing generalized anxiety disorder following Roux-en-Y Gastric Bypass surgery: • Which of the following SSRIs will be impacted by her altered GI physiological state? • Which SSRI is available in the most dosage forms to allow for alternative routes of administration? • Citalopram • Escitalopram • Fluoxetine • Paroxetine • Sertraline

21. Alternative Formulations & Sites of Absorption

22. Question: A 42 y/o female presents with ongoing generalized anxiety disorder following Roux-en-Y Gastric Bypass surgery: • Which of the following SSRIs will be impacted by her altered GI physiological state? • Which SSRI is available in the most dosage forms to allow for alternative routes of administration? • Citalopram • Escitalopram • Fluoxetine • Paroxetine • Sertraline

23. Question: A 42 y/o female presents with ongoing generalized anxiety disorder following Roux-en-Y Gastric Bypass surgery: • Which of the following SSRIs will be impacted by her altered GI physiological state?All (Greatest absorption in duodenum) • Which SSRI is available in the most dosage forms to allow for alternative routes of administration? • Citalopram • Escitalopram • Fluoxetine • Paroxetine • Sertraline

24. Alternative Formulations & Sites of Absorption

25. Question: A 37 y/o male presents with ongoing depression following Roux-en-Y Gastric Bypass surgery: • Which of the following SNRIs will be least impacted by his altered GI physiological state? • Which of the following SNRIs will be most impacted by his altered GI physiological state? • Desvenlafaxine • Duloxetine • Levomilnacipran • Venlafaxine

26. Question: A 37 y/o male presents with ongoing depression following Roux-en-Y Gastric Bypass surgery: • Which of the following SNRIs will be least impacted by his altered GI physiological state?Desvenlafaxine (Absorbed in ileum) • Which of the following SNRIs will be most impacted by his altered GI physiological state? Duloxetine (Absorbed in duodenum) • Desvenlafaxine • Duloxetine • Levomilnacipran • Venlafaxine

27. Conclusions: • Co-diagnoses of obesity and psychiatric illness may pose issues with absorption & therapeutic efficacy in patients with altered GI physiology • Gastric Bypass Surgery • Short Bowel Syndrome • Medications absorbed in the duodenum are most affected by RYGB • Absorption throughout small intestine → Moderately affected • Absorption primarily in ileum/colon → Least affected • Certain commercially-available dosage forms may be efficacious when administered via alternative routes

28. Implications: What’s Next? • Limited research available • MAOIs • Phenelzine, Selegiline, Tranylcypromine • TCAs • Amitriptyline, Desipramine, Doxepin, Imipramine • Other antidepressants • Bupropion, Mirtazapine, Vilazodone, Trazodone

29. References • CDC Data & Statistics: NCHS Data Brief: https://www.cdc.gov/nchs/data/databriefs/db219.pdf • Roerig, J. L.; Steffen, K. (2015) Psychopharmacology and Bariatric Surgery. Eur. Eat. Disorders Rev., 23: 463–469. doi: 10.1002/erv.2396. • Segal, J.B., Clark, J.M., Shore, A.D. et al. OBES SURG (2009) 19: 1646. - references for second bullet • Seaman JS, Bowers SP, Dixon P, Schindler L. Dissolution of common psychiatric medications in a Roux-en-Y gastric bypass model. Psychosomatics. 2005;46(3):250-3. • Hamad, G. G., Helsel, J. C., Perel, J. M., Kozak, G. M., McShea, M. C., Hughes, C., … Wisner, K. L. (2012). The Effect of Gastric Bypass on the Pharmacokinetics of Serotonin Reuptake Inhibitors. The American Journal of Psychiatry, 169(3), 256–263. http://doi.org/10.1176/appi.ajp.2011.11050719