1. Christian Askren, Christopher Fox, Sonja Hutchens, Marjorie Peck
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 Citalopram Escitalopram Fluoxetine Paroxetine
No information on:
Paroxetine
Duodenum
Citalopram
Fluoxetine
Sertraline
Ileum
Fluoxetine
Sertraline
Citalopram
Duodenum
Escitalopram
Fluoxetine
Duodenum (100%)
Ileum (66%)
Colon (15%)
Paroxetine
Sertraline

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

10. SSRIs vs. SNRIs SSRIs SNRIs
Plasma levels significantly reduced 1-3 mo. post-RYGB5
Plasma levels normalize 6-12mo. post-RYGB in 75% of patients5
Plasma levels largely unaffected post-RYGB
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
Amitriptyline
Clomipramine- small intestine
Desipramine
Doxepin
Imipramine
Nortriptyline

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

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

16. Mood Stabilizers No information on: Lithium Duodenum Lamotrigine
Upper small intestine
Valproate
Lower small intestine
Carbamazepine
Carbamazepine- lower intestine
Lamotrigine-duodenum
Lithium-no info
Valproate- upper region of the small intestine

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
A study conducted by Seaman etc al, concluded that lithium had an increase in dissolution in post roux-en-Y environment which could lead to toxicity if patient was current on their pre-procedure dose.
Quetiapine, Ziprasidone, and Fluoxetine have a greater dissolution rate in a normal ( pre-roux-en-y) environment.

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. Antipsychotics No information on: Asenapine Brexipiprazole Cariprazine
Chlorpromazine
Clozapine
Fluphenazine
Haloperidol
Loxapine
Lurasidone
Paliperidone
Perphenazine
Quetiapine
Risperidone
Thioridazine
Thiothixene
Trifuoperazine
Ziprasidone
Duodenum
Aripirazole
Iloperidone
Small intestine
Olanzapine
Colon
Olanzapine
Asenapine
Aripirazole- duodenum
Brexipiprazole
Cariprazine
Chlorpromazine
Clozapine
Fluphenazine
Haloperidol
Iloperidone- duodenum, jejunum and ileum
Loxapine
Lurasidone
Olanzapine- small intestine and colon
Paliperidone
Perphenazine
Quetiapine
Risperidone
Thioridazine
Thiothixene
Trifluoperazine
Ziprasidone

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
SSRI Antidepressants
Medication
Dosage Form
Primary Absorption Site
Citalopram
Duodenum
Escitalopram
Fluoxetine
Duodenum (100%)
Ileum (66%)
Colon (15%)
Paroxetine
Sertraline

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
SNRI Antidepressants
Medication
Dosage Forms
Absorption Site
Desvenlafaxine
Ileum (lowest in duodenum/colon)
Duloxetine
Duodenum (lowest in stomach)
Levomilnacipran
Venlafaxine
Throughout small intestine

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
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.

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:
Roerig, J. L.; Steffen, K. (2015) Psychopharmacology and Bariatric Surgery. Eur. Eat. Disorders Rev., 23: 463–469. doi: /erv.2396.
Segal, J.B., Clark, J.M., Shore, A.D. et al. OBES SURG (2009) 19: 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.