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

Trial Summary

What is the purpose of this trial?

This trial is testing if a high-fat, low-carb diet can help adults with Bipolar Disorder. The diet increases a substance that might reduce severe mood swings. Researchers will use various methods to study its effects on brain activity and emotions. The diet may have mood-stabilizing properties.

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.

What data supports the effectiveness of the ketogenic diet as a treatment for bipolar disorder?

The ketogenic diet, known for its success in treating epilepsy, may help stabilize mood in bipolar disorder. Online reports and studies suggest it could be beneficial due to its effects on brain energy and sodium levels, which are important for mood stabilization. ^{1 2 3 4 5}

Is the ketogenic diet generally safe for humans?

The ketogenic diet has been used for conditions like epilepsy, and while it can be effective, it may cause side effects such as poor growth, high cholesterol levels, and kidney stones, especially in children. However, newer flexible versions of the diet may help reduce these risks. ^{3 6 7 8 9}

How does the ketogenic diet treatment for bipolar disorder differ from other treatments?

The ketogenic diet is unique for bipolar disorder as it focuses on altering metabolism by reducing carbohydrate intake and increasing fat consumption, which may influence brain energy use and neurotransmitter balance, unlike traditional medications like lithium that target mood stabilization through chemical pathways. ^{10 11 12 13 14}

Research Team

Mary L Phillips, MD, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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) 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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

The use of the ketogenic diet in the treatment of psychiatric disorders. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The ketogenic diet may have mood-stabilizing properties. [2008]

3. Italy pubmed.ncbi.nlm.nih.gov

Ketogenic diet experience at Ondokuz Mayıs University. [2021]

4. India pubmed.ncbi.nlm.nih.gov

The ketogenic diet and other dietary treatments for refractory epilepsy in children. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Ketosis and bipolar disorder: controlled analytic study of online reports. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

The ketogenic diet for Dravet syndrome and other epileptic encephalopathies: an Italian consensus. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the ketogenic diet for intractable childhood epilepsy: Korean multicentric experience. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

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

10. Netherlands 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. [2020]

11. Korea (South) pubmed.ncbi.nlm.nih.gov

[The Management of Common Bile Duct Stones]. [2018]

12. Germany pubmed.ncbi.nlm.nih.gov

Suspected common bile duct stones: reduction of unnecessary ERCP by pre-procedural imaging and timing of ERCP. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Laparoscopic management after failed endoscopic stone removal in nondilated common bile duct. [2022]

14. Greece pubmed.ncbi.nlm.nih.gov

Long term outcomes of choledochoduodenostomy for common bile duct stones in the era of laparoscopy and endoscopy. [2015]