Considerations for Psychotropic Medication in Patients with Altered Gastrointestinal Physiology Askren R, Fox C, Hutchens S, Peck M, Kauer J. University of Iowa College of Pharmacy Background Patients with psychiatric illness can have altered GI pathophysiology for multiple reasons, including medical complications from suicide attempts or psychotropic medication use leading to short bowel syndrome or bariatric surgery in patients with comorbid mental illness and obesity. According to the National Institute of Health (NIH) 35% of the U.S. population remains obese (BMI ≥ 30kg/m2). 20-70% of morbidly obese patients ( BMI ≥ 40 kg/ m2) are also afflicted with a current or past psychiatric disorder. 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. 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. Results Limitations Medication Absorption Sites Commercially-Available Dosage Forms Mood Stabilizers Carbamazepine Lower intestine Oral tablet (IR, ER, chewable) ER capsule Oral suspension Valproate Upper region of the small intestine IV liquid Oral syrup DR sprinkle Oral capsule(IR, DR) Antipsychotics Aripiprazole Primarily throughout duodenum IM (Syringe, powder for suspension) Oral tablet ODT Oral solution Iloperidone Greatest metabolism in duodenum (44%),Jejunum (32%) Ileum (24%) Olanzapine Small intestine and colon IM(long acting, IR) SSRIs Citalopram Duodenum Escitalopram Fluoxetine Throughout GI tract; Primarily Duodenum Sertraline SNRIs Desvenlafaxine Ileum (primary) Oral tablet(ER) Duloxetine Oral capsul(DR) Venlafaxine Small intestine Oral tablet (IR, ER) Oral capsule(ER) TCAs Clomipramine Throughout small intestine Oral capsule Isocarboxazid MAOIs Other Antidepressants Vortioxetine Drug Classes Medications Without Absorption Site Information SSRIs & SNRIs Paroxetine, Levomilnacipran Tricyclic Antidepressants Amitriptyline, Desipramine, Doxepin, Imipramine, Nortriptyline MAOIs Phenelzine, Selegiline, Tranylcypromine Other Antidepressants Bupropion, Mirtazapine, Vilazodone, Trazodone Mood Stabilizers Lithium Antipsychotics Asenapine, Brexipiprazole, Cariprazine, Chlorpromazine, Clozapine, Fluphenazine, Haloperidol, Loxapine, Lurasidone, Paliperidone, Perphenazine Quetiapine, Risperidone, Thioridazine, Thiothixene, Trifuoperazoine, Ziprasidone Discussion and Future Research Of the psychotropic medications included in this literature evaluation, areas of interest include primary site(s) of absorption within the GI tract, a description of commercially-available dosage forms currently in production, and any clinical efficacy data in patients with altered gastrointestinal physiology.  Medications that are available in a variety of dosage forms may be of particular benefit to the patient population studied in that they facilitate opportunities for alternative routes of psychotropic medication administration. Upon evaluation of existing literature, it was found that plasma levels of SNRI antidepressants administered post-RYGB intervention were more consistent and robust compared to SSRI alternatives.  Following RYGB, SSRI antidepressants tend to exhibit a marked reduction in plasma levels during the initial 3 months following intervention.  While both SNRI and SSRI plasma levels tend to return to near-baseline levels 12 months post-intervention, SNRI levels appear to be affected less by altered GI physiology than SSRI plasma levels. In the absence of published literature for specific medications, respective drug manufacturers were contacted for information regarding site of absorption within the GI tract for each medication in question.  Because limited data exists for new psychotropic agents—such as atypical antipsychotics—this literature review found sparse data regarding primary site(s) of absorption and clinical efficacy in patients with altered GI physiology.  Future directions include revisiting the clinical literature once additional studies are performed utilizing these agents.  Objectives Identify literature on psychotropic medication use after GI surgical interventions or in patients with abnormal GI physiology. Collect medication information from medication manufacturers regarding each drug’s absorption site. Summarize drug information collected in table format to help facilitate dosing recommendations in patients with abnormal GI physiology. Methods 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. Conclusions While bariatric surgery and short bowel syndrome are not uncommon comorbidities in patients with psychiatric illness, there is limited literature to guide clinicians about absorption of psychotropic medications in patients with these conditions.  Even drug manufacturers have limited information available regarding absorption sites of psychotropic medications. Medications absorbed in the duodenum are most affected by RYGB Absorption throughout small intestine → Moderately affected Absorption primarily in ileum/colon → Least affected Alternative dosage forms that bypass the GI tract (e.g. transdermal and rectal) are not commercially available for most psychotropic medications, making an understanding of where these medications are absorbed in the GI tract a very important consideration for choosing therapy in patients with altered GI pathophysiology and comorbid psychiatric illness.