Shebani Sethi MD, ABOM
Clinical Assistant Professor, Psychiatry and Behavioral Sciences
Bio
Dr. Sethi is a Clinical Assistant Professor in the Department of Psychiatry and Behavioral Sciences and founding Director of the first academic Metabolic Psychiatry Clinical program since 2015. She is board-certified in both Psychiatry and Obesity Medicine with additional expertise in adult eating disorders. She completed her residency in Psychiatry at Stanford University and specialized training in Obesity Medicine at Duke Medical Center. Dr. Sethi received her MD jointly from Duke University School of Medicine and the National University of Singapore. She received a Masters degree in Biotechnology from Johns Hopkins University. Metabolic Psychiatry is a term she developed to describe the emerging clinical discipline focused on the integrative study and treatment of metabolic dysfunction and the relationship to mental illness. Dr. Sethi's approach to psychiatric treatment incorporates detection and treatment of metabolic abnormalities, principles of obesity medicine, nutrition and metabolism. She was awarded funding by the Obesity Treatment Foundation and Baszucki Brain Foundation to study the effectiveness of a low - carbohydrate ketogenic dietary intervention in patients with bipolar illness or schizophrenia with overlapping metabolic abnormalities. Her previous research included a pilot randomized clinical trial testing an FDA-approved obesity medication for binge-eating disorder and bulimia nervosa at Stanford University funded by SPARK. She is a recipient of the Kuen Lau Bipolar Research Award and the Symonds Fellow Award from the Association of Women Psychiatrists for innovation in psychiatry and contributions to women’s health. She is a member of the Obesity Medicine Association, the American Psychiatric Association, and served on the council of the Northern California Psychiatric Association.
Clinical Focus
- Psychiatry
- Obesity Medicine
- Adult Eating Disorders
- Metabolic Syndrome
- Metabolic Psychiatry
Academic Appointments
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Clinical Assistant Professor, Psychiatry and Behavioral Sciences
Administrative Appointments
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Founding Director, Metabolic Psychiatry Clinic, Stanford University School of Medicine (2019 - Present)
Honors & Awards
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Kuen Lau Bipolar Research Award, Stanford Department of Psychiatry (2021)
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Metabolic Psychiatry Research Fund, Baszucki Brain Foundation (2021)
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Obesity Treatment Foundation Grant Award, Obesity Medicine Association (2018)
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Symonds Fellow Award, Association of Women Psychiatrists (2016)
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ASCP Clinical Trial Scholarship, American Society of Clinical Psychopharmacology (2016)
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Recipient, The Coaching Fellowship (2015)
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Scholar, Stanford Society of Physician Scholars (2015)
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Clinical and Translational Science Award (CTSA) Seed Grant, Stanford Office of Community Health (2010-2012)
Professional Education
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Board Certification: American Board of Obesity Medicine, Obesity Medicine (2020)
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Board Certification: American Board of Psychiatry and Neurology, Psychiatry (2018)
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Residency, Stanford University Medical Center, Psychiatry (2017)
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Internship, Stanford University Medical Center, Psychiatry (2014)
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MD, National University of Singapore, Medicine (2013)
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MD, Duke University School of Medicine, Medicine (2013)
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MS, Johns Hopkins University, Biotechnology (2007)
Current Research and Scholarly Interests
Improving metabolic and mental health through dietary metabolic therapies, pharmacological optimization, and other lifestyle interventions in those with severe mental illness, such as bipolar disorder, schizophrenia, major depression is a major focus of her research. Clinical and academic interests include management of psychiatric disorders with co-morbid obesity, insulin resistance, metabolic dysfunction and/or eating disorders, particularly binge eating disorder and bulimia nervosa.
Clinical Trials
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Can Neural Network Instability in Schizophrenia be Improved With a Very Low Carbohydrate Ketogenic Diet?
Recruiting
Wide ranging cognitive deficits are major drivers of functional decline and poor outcomes in people with schizophrenia (SZ) and bipolar disorder (BD). Medications do not target pathophysiological mechanisms thought to underlie these deficits. In the search for interventions targeting underlying cognitive impairment in SZ and BD, we look comprehensively beyond just the brain and to the potential role of dysfunctional systemic metabolism. Disrupted insulin and glucose metabolism are seen in medication-naïve first-episode SZ, suggesting that SZ itself, and not just the medications used to treat it, is associated with risk of Type 2 diabetes, cardiovascular morbidity and mortality, and more generally, accelerated aging. Even young people with SZ have increased risk of metabolic disease and cognitive deficits. Sadly, their life span is shortened by 15-20 years. BD is associated with similar but less severe disruptions in glucose and insulin metabolism and life expectancy. Although the human brain is 2% of the body's volume, it consumes over 20% of its energy, and accordingly, the brain is particularly vulnerable to the dysregulation of glucose metabolism seen in SZ and BD. While glucose is considered to be the brain's default fuel, ketones provide 27% more free energy and are a major source of energy for the brain. Ketones prevent or improve various age-associated diseases, and a ketogenic diet (70% fat, 20% protein, 10% carbohydrates) has been posited as an anti-aging and dementia antidote. The premise of the work is based on recent evidence that ketogenic diets improve dynamic neural network instability, related to cognitive deficits, aging, and Type 2 diabetes (Mujica-Parodi et al., Proc Natl Acad Sci U S A. 2020;117(11):6170-7.). The rigor of the work rests on findings of (1) poor cerebral glucose homeostasis in SZ and BD, (2) neural network instability in SZ and BD, and (3) direct effects of ketosis on network instability. Unknown is whether ketogenic diets can improve network instability in people with SZ and BD.
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FDA Approved Medication to Reduce Binge Eating and/or Purging
Not Recruiting
This study will demonstrate the efficacy of Qsymia versus placebo in treating bulimia nervosa and binge eating disorder.
Stanford is currently not accepting patients for this trial. For more information, please contact Debra L Safer, MD, 650-723-7928.
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Impact of a Ketogenic Diet on Metabolic and Psychiatric Health in Patients With Bipolar Illness
Not Recruiting
To initiate a low-carbohydrate, high-fat (LCHF) or ketogenic dietary (KD) intervention among a cohort of outpatients with bipolar illness who also have metabolic abnormalities, overweight/obesity, and/or are currently taking psychotropic medications experiencing metabolic side effects.
Stanford is currently not accepting patients for this trial. For more information, please contact Diane E Wakeham, PhD, 650-736-5243.
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Impact of a Ketogenic Diet on Metabolic and Psychiatric Health in Patients With Bipolar or Schizophrenia Illness
Not Recruiting
To initiate a low-carbohydrate, high-fat (LCHF) or ketogenic dietary (KD) intervention among a cohort of outpatients with either schizophrenia or bipolar illness who also have metabolic abnormalities, overweight/obesity, and/or are currently taking psychotropic medications experiencing metabolic side effects.
Stanford is currently not accepting patients for this trial.
All Publications
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The Role of Ketogenic Metabolic Therapy on the Brain in Serious Mental Illness: A Review
Journal of Psychiatry & Brain Sciences
2022; 7:e220009.
View details for DOI 10.20900/jpbs.20220009
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Ketogenic Diet as a Metabolic Treatment for Mental Illness.
Current Opinion in Endocrinology, Diabetes and Obesity.
2020 ; 27 (5)
View details for DOI 10.1097/MED.0000000000000564
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Low Carbohydrate Ketogenic Therapy as a Metabolic Treatment for Binge Eating and Ultra-processed Food Addiction.
Current Opinion Endocrinology, Diabetes and Obesity
2020; 27 (5)
View details for DOI 10.1097/MED.0000000000000571
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Treating Binge Eating and Food Addiction Symptoms with Low-carbohydrate Ketogenic Diets: A Case Series
Journal of Eating Disorders.
Biomed Central .
2020
Abstract
Background: Many patients with obesity and comorbid binge eating symptoms present with the desire to lose weight. Although some studies suggest that dietary restriction can exacerbate binge eating, others show dietary restriction is associated with significant reductions in binge eating. The effect of a particular type of dieting on binge eating, the ketogenic diet (a high fat, moderate protein, very low carbohydrate diet), is not known. Case presentations: We report on the feasibility of a low-carbohydrate ketogenic diet initiated by three patients (age 54, 34, and 63) with obesity (average BMI 43.5 kg/m2) with comorbid binge eating and food addiction symptoms. All patients tolerated following the ketogenic diet (macronutrient proportion 10% carbohydrate, 30% protein, and 60% fat; at least 5040 kJ) for the prescribed period (e.g., 6–7 months) and none reported any major adverse effects. Patients reported significant reductions in binge eating episodes and food addiction symptoms including cravings and lack of control as measured by the Binge-Eating Scale, Yale Food Addiction Scale, or Yale- Brown Obsessive-Compulsive Scale modified for Binge Eating, depending on the case. Additionally, the patients lost a range of 10–24% of their body weight. Participants reported maintenance of treatment gains (with respect to weight, binge eating, and food addiction symptoms) to date of up to 9–17 months after initiation and continued adherence to diet. Conclusions: Although the absence of control cases precludes conclusions regarding the specific role of ketogenic diets versus other forms of dietary restriction, this is the first report to demonstrate the feasibility of prescribing a ketogenic diet for patients with obesity who report binge eating and food addiction symptoms. Further research should seek to reproduce the observed effects in controlled trials as well as to explore potential etiologies. Keywords: Binge eating, Food addiction symptoms, Obesity, Ketogenic diet, Dietary restriction
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A Randomized, Placebo‐controlled Crossover Trial of Phentermine‐topiramate ER in Patients with Binge‐eating Disorder and Bulimia Nervosa
International Journal of Eating Disorders
2019
View details for DOI 10.1002/eat.23192
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Ketogenic Diet as a Metabolic Therapy for Bipolar Disorder: Clinical Developments
Journal of Affective Disorders Reports
2022
View details for DOI 10.1016/j.jadr.2022.100457
- Ketogenic Diet as a Metabolic Therapy for Bipolar Disorder: Clinical Developments Research Square Preprint . 2021
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Ketogenic diet as a metabolic treatment for mental illness.
Current opinion in endocrinology, diabetes, and obesity
2020; 27 (5): 269-274
Abstract
Ketogenic diets, which have been used to treat drug-refractory paediatric epilepsy for over 100 years, are becoming increasingly popular for the treatment of other neurological conditions, including mental illnesses. We aim to explain how ketogenic diets can improve mental illness biopathology and review the recent clinical literature.Psychiatric conditions, such as schizophrenia, depression, bipolar disorder and binge eating disorder, are neurometabolic diseases that share several common mechanistic biopathologies. These include glucose hypometabolism, neurotransmitter imbalances, oxidative stress and inflammation. There is strong evidence that ketogenic diets can address these four fundamental diseases, and now complementary clinical evidence that ketogenic diets can improve the patients' symptoms.It is important that researchers and clinicians are made aware of the trajectory of the evidence for the implementation of ketogenic diets in mental illnesses, as such a metabolic intervention provides not only a novel form of symptomatic treatment, but one that may be able to directly address the underlying disease mechanisms and, in so doing, also treat burdensome comorbidities (see Video, Supplementary Digital Content 1, http://links.lww.com/COE/A16, which summarizes the contents of this review).
View details for DOI 10.1097/MED.0000000000000564
View details for PubMedID 32773571
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Low carbohydrate ketogenic therapy as a metabolic treatment for binge eating and ultraprocessed food addiction.
Current opinion in endocrinology, diabetes, and obesity
2020; 27 (5): 275-282
Abstract
The aim of this study was to highlight the recent advancements and future directions for potential use of a low carbohydrate ketogenic dietary approach to treat binge eating and ultraprocessed food addiction. Herein, we explore proposed mechanisms of why a diet low in refined carbohydrates, processed sugar and higher fat content may be helpful in alleviating symptoms.Emerging evidence suggests there may be a metabolic role in development of maladaptive eating. These findings broaden our understanding of eating psychopathology causes. Ultraprocessed, refined or high glycemic index carbohydrates are a possible trigger mediating neurochemical responses similar to addiction. The carbohydrate-insulin model of obesity supports observations of these foods triggering abnormal blood sugar and insulin spikes subsequently leading to changes in metabolic and neurobiological signaling. This results in overeating symptoms and hunger exacerbation, which differs from observed effects of healthy fat consumption and lack of similar insulin spikes. As supported in recent case series, significantly reducing or abstaining from these addictive-like ultraprocessed foods and highly refined carbohydrates could be considered a treatment approach.The current review highlights recent and pertinent evidence with respect to theoretical and practical application of low carbohydrate ketogenic therapeutic approaches for ultraprocessed food addiction and binge eating symptoms. VIDEO ABSTRACT:.
View details for DOI 10.1097/MED.0000000000000571
View details for PubMedID 32773576
- If Americans were healthier, we could have been better prepared for this pandemic. The Hill Op-Ed. 2020
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Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa.
Contemporary clinical trials
2018; 64: 173–78
Abstract
Bulimia nervosa (BN) and binge eating disorder (BED) are associated with severe psychological and medical consequences. Current therapies are limited, leaving up to 50% of patients symptomatic despite treatment, underscoring the need for additional treatment options. Qsymia, an FDA-approved medication for obesity, combines phentermine and topiramate ER. Topiramate has demonstrated efficacy for both BED and BN, but limited tolerability. Phentermine is FDA-approved for weight loss. A rationale for combined phentermine/topiramate for BED and BN is improved tolerability and efficacy. While a prior case series exploring Qsymia for BED showed promise, randomized studies are needed to evaluate Qsymia's safety and efficacy when re-purposed in eating disorders. We present a study protocol for a Phase I/IIa single-center, prospective, double-blinded, randomized, crossover trial examining safety and preliminary efficacy of Qsymia for BED and BN.Adults with BED (n=15) or BN (n=15) are randomized 1:1 to receive 12weeks Qsymia (phentermine/topiramate ER, 3.75mg/23mg-15mg/92mg) or placebo, followed by 2-weeks washout and 12-weeks crossover, where those on Qsymia receive placebo and vice versa. Subsequently participants receive 8weeks follow-up off study medications. The primary outcome is the number of binge days/week measured by EDE. Secondary outcomes include average number of binge episodes, percentage abstinence from binge eating, and changes in weight/vitals, eating psychopathology, and mood.To our knowledge this is the first randomized, double-blind protocol investigating the safety and efficacy of phentermine/topiramate in BED and BN. We highlight the background and rationale for this study, including the advantages of a crossover design.Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824.
View details for PubMedID 29038069
- Could Pokémon Go Have Some Mental Health Benefits? American Psychiatric Association . Washington DC. 2016