Ketogenic Diet for Bipolar Disorder

Overseen By Jill Morris-Tillman

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must be taking: Atypical antipsychotics, lithium

Must not be taking: Anticoagulants

Disqualifiers: Head injury, Neurological disorder, SUD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

107 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how a ketogenic diet, high in fats and low in carbohydrates, affects brain activity and emotions in individuals with Bipolar Disorder (BD). Participants will follow both a ketogenic and a non-ketogenic diet to assess the impact on their condition. The study is open to adults with BD who are not currently on a ketogenic diet, making it ideal for those interested in exploring dietary changes as part of their mental health management. As an unphased trial, it provides a unique opportunity to explore innovative dietary approaches for managing mental health.

Do I need to stop my current medications to join the trial?

Participants with Bipolar Disorder can continue taking their current medications, such as atypical antipsychotics, lithium, antidepressants, and anxiolytics. The trial does not require stopping these medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the ketogenic diet, high in fat and low in carbohydrates, is generally safe for most people. In studies involving individuals with bipolar disorder, participants followed this diet without major safety issues. For instance, a small study found that participants adhered to the diet, deriving most of their energy from fats, without serious side effects. Another study suggested that this diet might improve overall health, potentially aiding in the management of mood disorders.

Some individuals might experience fatigue or headaches when starting the diet, but these symptoms usually improve as the body adapts. The ketogenic diet is also under study for other health conditions, showing promise and appearing reasonably safe. However, following advice from healthcare professionals is crucial, especially when managing a condition like bipolar disorder. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using a ketogenic diet for bipolar disorder because it offers a non-pharmacological approach that may stabilize mood by altering brain metabolism. Unlike standard treatments like mood stabilizers and antipsychotics, which often come with significant side effects, a ketogenic diet focuses on consuming high-fat, low-carbohydrate foods to shift the body’s energy source from glucose to ketones. This change in metabolic state is thought to potentially provide a more natural balance to brain function, offering a new avenue for managing bipolar symptoms without medication. Additionally, this dietary approach could be appealing for those looking for lifestyle-based interventions as part of their mental health management.

What evidence suggests that this trial's treatments could be effective for Bipolar Disorder?

Research suggests that the ketogenic diet might help treat bipolar disorder. In several studies, individuals following this high-fat, low-carbohydrate diet experienced improvements in mental health. Specifically, one study found that the diet reduced mood swings and stabilized emotions in those with bipolar disorder. This trial will compare the effects of a ketogenic diet to a non-ketogenic diet in participants with bipolar disorder. Participants will alternate between these diets in different phases of the study. Although more research is needed, these findings indicate that the ketogenic diet could be a helpful option for managing bipolar disorder. ^{1 2 6 7 8}

Who Is on the Research Team?

Mary L Phillips, MD, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

Adults aged 18-30 with Bipolar Disorder, either hypomanic or euthymic, who are taking certain BD medications can join. Healthy controls without psychiatric history are also needed. Exclusions include head injury, systemic diseases, substance abuse (except limited cannabis), poor English understanding, and specific medical conditions.

Inclusion Criteria

I have bipolar disorder, with more manic than depressive symptoms, and I'm on medication.

I have bipolar disorder, am stable on my medication, and my mood scores are low.

I am healthy, have no psychiatric history, and match the sex of the BD group participants.

Exclusion Criteria

I am not sex-matched with BD groups and have a psychiatric history.

BD hypomanic group: Must be meeting sex proportions: not 50% female, Must be meeting diagnosis proportions: not 50:50% BDI:II (DSM-5), Diagnosis of BD in a depressive, manic, or euthymic episode, Young Mania Rating Scale score(YMRS)10 or lower, Score 8 or higher on Hamilton Rating Scale for Depression(HRSD), Using psychotropic medications other than those allowed in inclusion criteria, Head circumference larger than about 58 cm (size restriction of 7Tesla (7T) scanner)

BD euthymic group: Not meeting sex proportion: not 50% female, Not meeting diagnosis proportion: not 50:50% BDI:II, Diagnosis of BD in a depressive, hypomanic, or manic episode, Score 8 or higher on YMRS, Score 8 or higher on HRSD, Using psychotropic medications other than those allowed in inclusion criteria

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Baseline assessments including fasting hepatic function panel, fasting glucose, and neuroimaging scans

1 week

1 visit (in-person)

First Dietary Phase

Participants with Bipolar Disorder consume either a ketogenic or non-ketogenic diet, with mood and energy monitoring

8-10 weeks

Continuous monitoring (at-home)

Second Dietary Phase

Participants switch diets (from ketogenic to non-ketogenic or vice versa), with continued mood and energy monitoring

8-10 weeks

Continuous monitoring (at-home)

Follow-up

Participants are monitored for safety and effectiveness after dietary interventions

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Diet
• No diet
• Non-ketogenic Diet

Trial Overview

The trial is testing the effects of a ketogenic diet versus no diet change or a non-ketogenic diet on brain function and mood in people with Bipolar Disorder. Participants will be monitored to see how their brain activity and emotional state respond to dietary changes.

How Is the Trial Designed?

Group I: No diet Experimental Treatment 1 Intervention

Participants without Bipolar Disorder will not participate in the diet phases of the study

Group II: 1st phase Non-ketogenic Diet / 2nd phase Ketogenic Diet Experimental Treatment 2 Interventions

Participants with Bipolar Disorder will consume a non-ketogenic diet for the first phase of the study and then a ketogenic diet for the second phase of the study

Group III: 1st phase Ketogenic Diet / 2nd phase Non-ketogenic Diet Experimental Treatment 2 Interventions

Participants with Bipolar Disorder will consume a ketogenic diet for the first phase of the study and then a non-ketogenic diet for the second phase of the study

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

Baszucki Brain Research Fund

Collaborator

Trials

8

Recruited

330+

Published Research Related to This Trial

The ketogenic diet has shown significant efficacy in reducing seizure frequency in children with refractory epilepsy, with about two-thirds of patients experiencing a notable decrease and one-third becoming nearly seizure-free.

There is potential for the ketogenic diet to act as a mood stabilizer in bipolar disorder, as it may improve brain energy metabolism and reduce intracellular sodium levels, which are common mechanisms of effective mood stabilizers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet may have mood-stabilizing properties. El-Mallakh, RS., Paskitti, ME.[2008]

The ketogenic diet, which is high in fat and low in carbohydrates, has been found to be more effective than many new antiepileptic drugs for treating refractory epilepsy.

There is a significant lack of awareness among pediatricians and neurologists regarding the ketogenic diet as a treatment option for epilepsy, highlighting the need for better education on this effective dietary intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet and other dietary treatments for refractory epilepsy in children. Sharma, S., Jain, P.[2021]

The ketogenic diet (KD) has been associated with several health concerns in children, including poor growth, dyslipidemia, and kidney stones, raising questions about its long-term safety.

Despite these concerns, emerging evidence suggests that the KD may offer beneficial long-term health effects beyond its primary use in controlling seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term health consequences of epilepsy diet treatments. Vining, EP.[2022]

The ketogenic diet is an effective non-drug treatment for childhood epilepsy that does not respond to medication, supported by international guidelines from studies in Germany and the United States.

An Italian collaborative study group has developed a consensus statement to standardize the management of the ketogenic diet, covering aspects like patient selection, dietary induction, and follow-up care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet for Dravet syndrome and other epileptic encephalopathies: an Italian consensus. Veggiotti, P., Burlina, A., Coppola, G., et al.[2017]

In an analysis of comments from 274 individuals with bipolar disorder, 85.5% reported positive effects on mood stabilization from a ketogenic diet, with a significant number experiencing lasting improvements for months to years.

The ketogenic diet was associated with a higher rate of significant mood stabilization compared to other dietary interventions, suggesting it may have beneficial effects on mood, potentially linked to its impact on mitochondrial function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketosis and bipolar disorder: controlled analytic study of online reports. Campbell, IH., Campbell, H.[2023]

The ketogenic diet (KD), characterized by high fat and low carbohydrate intake, has shown promise in reducing symptoms of various psychiatric disorders based on a review of 14 studies.

While the results indicate a positive response for individuals adhering to the KD, further research is needed to clarify the specific benefits and mechanisms of action in psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of the ketogenic diet in the treatment of psychiatric disorders. Tillery, EE., Ellis, KD., Threatt, TB., et al.[2023]

In a retrospective analysis of 14 patients on the ketogenic diet (KD) for epilepsy, 3 patients became seizure-free and 7 experienced a reduction of at least 50% in their seizures, demonstrating the diet's potential efficacy in managing resistant epilepsy.

Despite positive outcomes, some patients discontinued the KD due to issues like frequent infections, family concerns, and financial difficulties, highlighting the need for ongoing support and consideration of individual circumstances in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet experience at Ondokuz Mayıs University. Tekin, E., Serdaroğlu, FM., Şahin, Ş., et al.[2021]

Choledochoduodenostomy (CDD) is a safe and effective treatment for common bile duct stones (CBDS), with a very low recurrence rate of stones (0.06%) and no cases of serious complications like sump syndrome or cholangiocarcinoma reported in a study of 388 patients.

Long-term outcomes after CDD show significant improvements in quality of life, as measured by the Gastrointestinal Quality of Life Index (GIQLI), indicating that patients experience better overall health following the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term outcomes of choledochoduodenostomy for common bile duct stones in the era of laparoscopy and endoscopy. El Nakeeb, A., Askr, W., El Hanafy, E., et al.[2015]

In a study of 199 patients with refractory epilepsy, the ketogenic diet (KD) demonstrated significant efficacy, with 58% of patients experiencing a reduction in seizure frequency of over 50% after 6 months, and 33% becoming seizure-free.

While the KD is generally safe and effective, with most complications being mild, there were five reported deaths, highlighting the need for careful monitoring of patients, especially those with symptomatic and partial epilepsies who may have a higher risk of relapse after discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the ketogenic diet for intractable childhood epilepsy: Korean multicentric experience. Kang, HC., Kim, YJ., Kim, DW., et al.[2022]

The commentary highlights that newer, more flexible versions of the classic ketogenic diet for treating intractable epilepsy have shown similar effectiveness, making it a viable option for patients.

These flexible ketogenic diet therapies improve compliance and palatability, while also potentially reducing side effects, thanks to better initiation protocols and available resources for patients and healthcare professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Not your parents' ketogenic diet - Flexibility in 2020. Blackford, R.[2021]

Laparoscopic common bile duct exploration (LCBDE) is a safe and feasible procedure for patients with nondilated CBD who have had unsuccessful endoscopic stone removal, based on a study of 165 cases from 2011 to 2015.

The study found no significant differences in key outcomes such as operating time, hospital stay, or complication rates between patients with nondilated CBD and those with dilated CBD, suggesting that LCBDE can be effectively performed regardless of CBD diameter.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laparoscopic management after failed endoscopic stone removal in nondilated common bile duct. Jinfeng, Z., Yin, Y., Chi, Z., et al.[2022]

In a study of 76 patients with bipolar disorder on lithium therapy for at least one year, adherence to medication was found to be suboptimal, with a mean adherence score of 6.95 out of 10.

The study identified that positive attitudes towards lithium and having family support during psychiatric visits were significant predictors of better medication adherence, highlighting the importance of education and support in treatment compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-reported medication adherence and its correlates in a lithium-maintained cohort with bipolar disorder at a tertiary care centre in India. Singh, S., Kumar, S., Mahal, P., et al.[2020]

Endoscopic ultrasonography is highly effective for diagnosing common bile duct (CBD) stones, showing greater sensitivity compared to magnetic resonance cholangiopancreatography, which is crucial for early diagnosis and treatment.

For high-risk patients with CBD stones, single-stage laparoscopic CBD exploration combined with cholecystectomy is more effective and results in shorter hospital stays than the traditional approach of ERCP followed by laparoscopic cholecystectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Management of Common Bile Duct Stones]. Park, CH.[2018]

In a study of 707 patients with suspected common bile duct stones, 22% of ERCP procedures were negative for sludge or stones, indicating a significant rate of unnecessary procedures.

The likelihood of detecting CBD stones during ERCP was higher when pre-procedural imaging (EUS or MRCP) was performed within 2 days prior to the procedure, suggesting that timely imaging can improve diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suspected common bile duct stones: reduction of unnecessary ERCP by pre-procedural imaging and timing of ERCP. Sperna Weiland, CJ., Verschoor, EC., Poen, AC., et al.[2023]

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Ketogenic Diet Shows Promise for Bipolar Disorder

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