Weighing in on Bariatric Surgery’s

effect in Psychiatric Medicine

Jordan Clark, PharmD | May 2, 2018
PGY1 Pharmacy Resident
Objectives

Differentiate the various contemporary bariatric surgical

procedures and their implications on pharmacokinetics

Assess common post-surgical complications potentially

affecting a patient’s treatment plan

Analyze specific medications and dosage forms pertinent in

psychiatric pharmacotherapy

2
Prevalence of Obesity
438,479 of
Americans

10,319 of
Hoosiers

Centers for Disease Control and Prevention. National Center for Chronic
Disease Prevention and Health Promotion, Division of Nutrition, Physical 3
Activity, and Obesity. Data, Trend and Maps [online].
Bariatric Surgery

~200,000
surgeries in
the US per 60% of patients
year undergoing
bariatric surgery
have psychiatric
illness
Lim RB. Bariatric procedures for the management of severe obesity:
Descriptions. Uptodate 4
Krieger CA. Pharmacotherapy. 2017
Mental Health in Bariatric Patients

17% Binge
19% 12%
Eating
Depression Anxiety
Disorder

Dawes AJ, JAMA. 2016. 5

Indications for Surgery

BMI 35-39.9 kg/m2 BMI 30-34.9 kg/m2

with difficult-to-control
BMI ≥40 kg/m2 with an obesity- T2DM or dysmetabolic
related comorbidity syndrome X

Lim RB. Bariatric procedures for the management of severe obesity:

6
Descriptions. Uptodate.
Mechanisms of Weight Loss

Caloric
restriction
Neurohormonal
Malabsorption
effects

Weight
loss

Lim RB. Bariatric procedures for the management of severe obesity: Descriptions. Uptodate. 7
Roux-en-Y Gastric Bypass

8
Roux-en-Y Gastric Bypass Procedure

• Small stomach pouch ~ 30

mL in size
• Small intestine is divided
• Bottom portion is
connected to the “new”
stomach
• Top portion connected
to the intestine further
down for acids and
stomach enzymes

Bariatric Surgery Procedure. American Society for Metabolic and Bariatric Surgery.
Lim RB. Bariatric procedures for the management of severe obesity: Descriptions. Uptodate. 9
Roux-en-Y Gastric Bypass Mechanism

• Decreased caloric intake

• Decreased digestion of
food
• Changes GI hormones to
promote satiety and
suppress hunger
• Expected ~ 70% loss of
excess weight at 2 years
Roux-en-Y Gastric Bypass Disadvantages

• Complex operation – increased risk of complications, longer

hospital stays
• Long-term deficiencies in vitamin B12, iron, calcium, and folate
• Required dietary recommendations and life-long
vitamin/mineral supplementation

Bariatric Surgery Procedure. American Society for Metabolic and Bariatric Surgery.
Lim RB. Bariatric procedures for the management of severe obesity: Descriptions. Uptodate.
Sleeve Gastrectomy

12
Sleeve Gastrectomy Procedure

• ~80% of the stomach is

removed

Bariatric Surgery Procedure. American Society for Metabolic and Bariatric Surgery.
Lim RB. Bariatric procedures for the management of severe obesity: Descriptions. Uptodate.
13
Sleeve Gastrectomy Procedure

• Decreased caloric
intake
• Changes GI
hormones to
promote satiety and
suppress hunger
• Expected ~ 70% loss
of excess weight at 2
years

Bariatric Surgery Procedure. American Society for Metabolic and Bariatric Surgery.
Lim RB. Bariatric procedures for the management of severe obesity: Descriptions. Uptodate.
14
Sleeve Gastrectomy Disadvantages

• Non-reversible procedure
• Potential for long-term vitamin/mineral deficiencies
• Higher risk of leaks and GERD

Bariatric Surgery Procedure. American Society for Metabolic and Bariatric Surgery.
Lim RB. Bariatric procedures for the management of severe obesity: Descriptions. Uptodate.
15
Biliopancreatic diversion with duodenal switch

16
Biliopancreatic diversion with duodenal switch
Procedure

• Portion of the stomach is

removed
• Bypass a ~3/4 of the small
intestines
• Bypassed portion is
reconnected to the last
portion of the small
intestines to deliver bile
and pancreatic enzymes

17
Biliopancreatic diversion with duodenal switch
Procedure

• Reduces caloric intake

• Decreased absorption of
caloric and nutrients
• Changes GI hormones to
promote satiety and
suppress hunger
• Expected ~ 70-80% loss of
excess weight at 2 years

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Biliopancreatic diversion with duodenal switch
Disadvantage

• Highest complication rates and risk for mortality

• Longer hospital stay
• Greater potential for protein, vitamin, and mineral deficiencies
• Strict adherence to dietary and vitamin supplementation is
critical

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Gastric Band

20
Gastric Band Procedure

• Creates a small stomach

pouch with an inflatable band
around the upper portion of
the stomach
• Adjustable with saline
injected via a port under the
skin
• Allows progressive size
reduction of the stomach
opening

21
Gastric Band Procedure

• Promotes feeling of fullness

and satiety
• Decreases caloric intake
• Less patients losing at least
50% of excess body weight

22
Gastric Band Disadvantages

• Slower weight loss

• Additional complications: band slippage, erosion, mechanical
problems
• Requires strict diet adherence
• High rates of re-operation

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Previous Treatments

Jejunoileal bypass
• Diverts a long segment of the small bowel
• High complication rate and frequent need for revision

Vertical banded gastroplasty

• Upper part of the stomach is partitioned with a staple line and a tight outlet
wrapped by a mesh or ban
• Lack of sustained/desired weight loss as well as the high incidence of
complications

Lim RB. Bariatric procedures for the management of severe obesity: Descriptions. Uptodate.
 Investigational Treatments

Intragastric balloon
Vagal blockade
Aspiration therapy
One-anastomosis gastric bypass
Single anastomosis duodeno-ileal bypass
Endoluminal vertical gastroplasty
Endoscopic gastrointestinal bypass devices

Lim RB. Bariatric procedures for the management of severe obesity: Descriptions. Uptodate.
 Changes in Obesity

• Proportion of adipose tissue

• Total body water
Increased • Lean body mass
• Visceral organ mass
• Glomerular filtration rate (GFR)

McAlpine DE. Current Psychiatry. 2006.

26
General Pharmacokinetic Considerations

Acid-base changes in the stomach

Decreased surface area for drug absorption

Alteration of gastrointestinal enzymes

Extended-release products may have decreased absorption

De Sousa Prado Geraldo M, Int J Gen Med. 2014. 27

Studies of Psychiatric
Medications after Bariatric
Surgery

28
 Medication Dissolution

Antidepressants Anxiolytic/Sedatives Antipsychotics/misc

• TCA • Benzodiazepine • Typical

• SSRI • Buspirone antipsychotics
• SNRI • Trazodone • Atypical
• Bupropion • Zolpidem antipsychotics
• Lithium
• Methylphenidate
• Oxcarbazepine

Seaman JS, Psychosomatics. May-June 2005. 29

Medication Dissolution

Environments created to simulate RYGB and

normal GI tract

RYGB medications were crushed as often done

in practice

Each medication with 3 trials in each scenario

Seaman JS, Psychosomatics. May-June 2005. 30

Medication Dissolution
→ in RYBG compared to normal anatomy

Bupropion Amitriptyline Clozapine

Lithium Fluoxetine Olanzapine
Paroxetine Quetiapine
Sertraline Risperidone
Clonazepam Ziprasidone

Seaman JS, Psychosomatics. May-June 2005. 31

 Antidepressants
• Retrospective study involving 439 patients who underwent RYGB
procedure
• 23% with an increase in antidepressant use after surgery,
Cunninghan • 18% started a new class of antidepressants
et al.
• 16% had a decreased need of antidepressant treatment

• After RYGB, risk of decreased bioavailability of SSRI medications

Hamad et al.

De Sousa Prado Geraldo M, Int J Gen Med. 2014. 32

Antidepressants

Small single-sex cohort of 5 female gastric bypass patients (GBP) and matched
nonsurgical control taking sertraline 100 mg

Loss of absorptive area had greater impact on kinetics

AUC0-10.5h 124.45 ± 55.46 ng • h/mL in GBP compared to 314.80 ± 129.56 ng •

h/mL in nonsurgical patients (p=0.043)

Edwards A, Ann Pharmacother. 2012. 33

Venlafaxine ER

Extended-release venlafaxine compared to immediate release

after RYBG surgery at Mayo Clinic
• Prospective, nonblinded single-dose pharmacokinetic study
• 10 adults served as their own control

Venlafaxine ER 75-mg capsule—the first visit at least 1 week

before RYGB and the second 3–4 months after RYGB.
• Blood samples were collected over 48 hours

No statistically significant difference in the exposure to

venlafaxine or primary metabolite exposure

Krieger CA. Pharmacotherapy. 2017 34

Lithium

Case report on lithium toxicity

• 18 yoF with bipolar disorder on lithium 300 mg every morning and 600
mg every evening
• Vertical sleeve gastrectomy 5 weeks prior with a 70 lb weight loss over
the last 6 months
• Presented to ED with fatigue, diarrhea, and tremors
• Lithium level = 2.7 mmol/L requiring hemodialysis

Possible multifactorial cause: AKI, decreased clearance,

increased absorption

Alam A, Clinical Psychopharmacology and Neuroscience 2016. 35

Possible Complications

Dumping
Gastric ulcers Cholelithiasis
syndrome

Stenosis/
Nephrolithiasis Hernias
Obstruction

Vitamin and mineral deficiencies

Ellsmere JC. Late complications of bariatric surgical operations. Uptodate. 36

Conclusions

Education

Consider medication dosage form

Monitoring

37
References

1. Centers for Disease Control and Prevention. National Center for Chronic Disease Prevention and Health Promotion, Division of Nutrition, Physical Activity,
and Obesity. Data, Trend and Maps [online]. Accessed 4/23/18. Available at: https://www.cdc.gov/nccdphp/dnpao/data-trends-maps/index.html.
2. Bariatric Surgery Procedure. American Society for Metabolic and Bariatric Surgery. https://asmbs.org/patients/bariatric-surgery-procedures.
Accessed 4/20/18.
3. Lim RB. Bariatric procedures for the management of severe obesity: Descriptions. Uptodate. Last updated: 3/26/18.
4. Krieger CA, Cunningham JL, Reid JM, Langman LJ, Grothe KB, Clark MM, Dierkhising RA. Comparison of Bioavailability of Single-Dose Extended
Release Venlafaxine Capsules in Obese Patients Before and After Gastric Bypass Surgery. Pharmacotherapy. 2017 Nov;37(11):1374-1382.
5. Dawes AJ, Maggard-Gibbons M, Maher AR, Booth MJ, Miake-Lye I, Beroes JM, Shekelle PG. Mental Health Conditions Among Patients Seeking
and Undergoing Bariatric Surgery A Meta-analysis. JAMA.2016;315(2):150-163
6. McAlpine DE. How to adjust drug dosing after bariatric surgery. Current Psychiatry. 2006;5(1):27-28.
7. Seaman JS, Bowers SP, Dixon P, Schindler Libby. Dissolution of Common Psychiatric Medications in a Roux-en-Y Gastric Bypass Model.
Psychosomatics 46:3, May-June 2005.
8. De Sousa Prado Geraldo M, Luiz Affonso Fonseca F, Regina de Fatima VG, Feder D. The use of drugs in patients who have undergone bariatric
surgery. Int J Gen Med. 2014; 7: 219–224.
9. Edwards A, Ensom Mary HH. Pharmacokinetic Effects of Bariatric Surgery. Ann Pharmacother. 2012;46:130-136.
10. Alam A, Raouf S, Recio FO. Lithium Toxicity Following Vertical Sleeve Gastrectomy: A Case Report. Clinical Psychopharmacology and
Neuroscience 2016;14(3):318-320.
11. Ellsmere JC. Late complications of bariatric surgical operations. Uptodate. Last updated 7/14/17

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Weighing in on Bariatric Surgery’s
effect in Psychiatric Medicine
Jordan Clark, PharmD | May 2, 2018
PGY1 Pharmacy Resident