The present study is an open trial of ketogenic diets for adolescents and young adults (ages 12-21 yrs) in the depressive or mixed phases of bipolar disorder (BD). The investigators aim to determine whether combining standard of care pharmacological treatment for bipolar spectrum disorders with a 16-week ketogenic diet is well-tolerated and associated with improvements in depression, inflammatory and metabolic indicators, and executive functioning over the study period.
The experimental treatment in this study is a 16-week full ketogenic diet. Four study sites (UCLA, U Cincinnati, U Colorado and U Pittsburgh) will recruit 80 total youth (20 each) from bipolar specialty clinics. All youth eligible for the ketogenic therapy will be provided with the ketogenic diet and standard of care pharmacological treatment. During the diet therapy youth will be seen by a study child/adolescent psychiatrist at least once a month (and more frequently when needed), with the psychiatrist recommending and providing side effects monitoring and pharmacotherapy as clinically indicated.
The youth and caregivers will also meet with an expert dietitian who will coach all youth on maintaining the ketogenic diet (low carbs, high fats, medium protein) and making sure the child is tolerating the diet and getting enough liquid and nutrients, following the practice guidelines of the International Ketogenic Diet Study Group for treating youth. All youth and involved caregivers will also be provided will at least one motivational enhancement session to support them in goal setting and completion of the study elements.
Throughout the study the investigators will assess metabolic (e.g., blood ketones, HOMA-IR) and inflammatory indicators (e.g., C-reactive protein), both for safety reasons and to assess correlates of symptomatic change. Independent evaluators will assess youth every month regarding their symptoms (depression, mania, anxiety, psychosis), psychosocial functioning, and quality of life.
The investigators anticipate that the pilot will transpire over 24 months and be an important step toward establishing feasibility and acceptability of ketogenic therapy for this population, not only in terms of diet administration and compliance but also for obtaining symptomatic, metabolic and inflammatory measurements.
Youth must be ages 12 to 21 years old and speak English
Youth must be appropriate for outpatient treatment (i.e., not a danger to self or others; not acutely psychotic, suicidal or manic; not in need of partial or full hospitalization)
Youth must have a current BSD (bipolar I, II per DSM-5 criteria (Association, 2013) or other specified BSD by the University of Pittsburgh diagnostic criteria (Birmaher et al., 2006). The Pittsburgh other specified BSD criteria require recurrent and distinct 1-3 day periods (minimum 4 hours/day) in which there has been abnormally elevated, expansive, or irritable mood plus two (three, if irritable mood only) symptoms of mania that caused a change in functioning and totaled at least 4 days in the child's lifetime
Active symptoms: In the 2 weeks prior to study intake, participants must have had weekly depression Psychiatric Status Ratings (PSRs) of 3 (moderate) or higher (using the 1-6 depression severity scales from the Adolescent Longitudinal Follow-up Evaluation, or A-LIFE); or an interview-based Children's Depression Rating Scale, Revised (CDRS-R) score covering the prior 2 weeks of > 20. Youth may also enter with mixed symptoms (e.g., simultaneous elevations of > 3 on the PSR depression and hypomania scales, with Young Mania Rating Scale scores of 12 or higher), without meeting criteria for a full manic episode in the past month.
pregnancy or breastfeeding
underweight (BMI below 18.5) or wasting syndrome (e.g., anorexia cachexia)
current or history of anorexia nervosa
current disordered eating (bulimia or binge eating disorder)
Single group
Ketogenic Therapy
Other interventionDuring the keto therapy (16 weeks), the youth will participate in a strict ketogenic diet, with adjustments made as necessary from weekly dietitian coaching sessions.
Diet Adherence
The investigators will assess diet adherence primarily by the proportion of youth who maintain an average weekly ketone level of 1 mmol/L or above, as measured through daily blood ketone assays using the Keto Mojo device, a Bluetooth-enabled ketone and glucose testing kit.
Diet Tolerance
The investigators will assess diet tolerance primarily by calculating the proportion of youth staying on the diet. The investigators hypothesize 70-80% of youth will tolerate staying on the keto therapy throughout the 16-week treatment as verified by youth self report of continuance of the diet (combined with parent report if applicable). Youth with multiple weekly ketone levels at .5 mmol/L or below will be considered diet intolerant regardless of self-report.
Depression Symptom Improvement
The investigators hypothesize that youth who complied with the 16-week keto diet therapy will show statistically significant reductions in depressive symptoms from baseline to completion of the diet. Depressive symptoms will primarily be captured using the clinician-rated Children's Depression Rating Scale, Revised (CDRS-R). Scores range from 17 to 113, with higher scores indicating greater pathology or severity of depressive symptoms (worse outcome).
Bipolar Symptom Improvement
The investigators hypothesize that youth who complied with the 16-week keto diet therapy will show statistically significant reductions in bipolar mood instability from baseline to completion of the diet. Bipolar instability will primarily be captured using the clinician-rated Clinical Global Impression - Bipolar Disorder Severity Scale (CGI-BP). CGI-BP overall psychiatric illness scores range from 1 (normal, best outcome) to 7 (very severely ill, worse outcome) and capture severity of bipolar symptoms over the worst 7-day period in the past 2 weeks.
Youth Functional Improvement
The investigators hypothesize that youth who complied with the 16-week keto diet therapy will show statistically significant increases in Global Assessment of Functioning (GAF) scores. GAF measures an individual's overall psychological, social, and occupational functioning on a scale from 1 to 100, with higher scores indicating better functioning (better outcome).
Serum Inflammatory Biomarkers (CRP)
The investigators hypothesize that youth who complied with the 16-week keto diet therapy will show statistically significant decreases in C-reactive serum protein (CRP) IL-6/IL-10 inflammatory markers. Lower CRP signifies less inflammation (better outcome).
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University of California, Los Angeles
Lead sponsor
University of Cincinnati
Collaborator
University of Pittsburgh
Collaborator
University of Colorado, Denver
Collaborator
Advanced Ketogenic Therapies
Collaborator
Baszucki Family Foundation
Collaborator
