Ketogenic Diet in People With Schizophrenia

Schizophrenia is a serious mental disorder with a heterogenous presentation, lack of clear understanding of pathophysiology and only partially effective treatments. First-line antipsychotic drugs block dopamine, but many people continue to suffer from persistent positive or negative symptoms that cannot be fully treated with available medications. Recently, our group has found that dietary modulations have efficacy comparable to antipsychotic medications and that determining which patients could benefit from a personalized treatment framework is critical.

The ketogenic diet consists of low-carbohydrate, moderate protein and high fat intake inducing a state in which ketone bodies in the blood provide energy to the cells. In pharmacologic mouse models a ketogenic diet regimen resulted in complete restoration of normal behaviors, independent of strict caloric restriction and other work has suggested that a ketogenic diet may improve schizophrenia like deficits in rodents. An open label ketogenic diet study in the 1950s reported improvement in schizophrenia symptom. At least 7 additional case reports have found robust improvements or complete resolution of schizophrenia symptoms. Recently a retrospective study found robust and significant improvements in schizophrenia symptoms in 10 schizoaffective disorder patients treated with a ketogenic diet. In addition to psychiatric symptoms, improvements in metabolic outcomes have been demonstrated. However, to date, there have been no published double blind randomized controlled trials evaluating the effects of a ketogenic diet since few sites can conduct inpatient trials and have observation and control for food intake

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Key information

Conditions

Schizophrenia Mental Disorders Psychotic Disorders Schizo Affective Disorder Schizophrenia Spectrum and Other Psychotic Disorders

Age range

18 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Maryland Psychiatric Research Center (MPRC) Treatment Research Program (TRP)

Catonsville, Maryland, 21228, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Age 18- 64 years
Diagnostic and Statistical Manual (DSM-IV/DSM 5) diagnosis of schizophrenia or schizoaffective disorder
Antipsychotic regimen with no dose change in last 14 days
Minimum score of 45 on BPRS
Body mass index > 18.5
Ability to consent determined by a score of 10 or greater on the Evaluation to Sign Consent.

Exclusion criteria

Pregnant or lactating females
Type I diabetes or insulin dependent Type II diabetes
Current diagnosis of DSM 5 eating disorder
Heart failure
corrected QT interval (QTc) prolongation greater than or equal to 500ms
Significant kidney disease

Indicators for possible acute kidney injury (AKI) or moderate chronic kidney disease (CKD) based on some factors below. Each is not used individually but a clinician will determine based on the following:

Creatinine > 1.3mg/dL
Glomerular Filtration Rate (GFR) < 60 mL/min/1.73 m2
Renal tubular disorders
History of kidney transplantation
Significant liver disease.

Indicators for possible acute or chronic liver disease. Each is not used individually but a clinician will determine based on the following:

Prolonged International Normalized Ratio (INR) greater than or equal to 1.5, elevated bilirubin and aminotransferases (3x normal upper limit) and/or Complete Blood Count (CBC) abnormalities (thrombocytopenia, anemia)
Physical examination abnormalities (jaundice, icteric sclera, asterixis)
Alcohol use disorder (AUD) based on DSM 5 criteria for moderate AUD
History of liver disease (cirrhosis, Wilson disease, Gilbert disease, chronic hepatitis, autoimmune hepatitis, primary biliary cirrhosis (PBC), primary Sclerosing Cholangitis (PSC) alpha-1 antitrypsin deficiency, hereditary hemochromatosis, Budd-Chiari syndrome)
History of liver transplantation
Porphyria
Genetic disorders that affect fat metabolism (Gaucher disease, Tay-Sachs disease, medium-chain acyl-CoA dehydrogenase deficiency (MCADD)
Carnitine deficiency syndromes (primary carnitine deficiency, carnitine palmitoyltransferase deficiency, carnitine translocase deficiency)
Pyruvate kinase deficiency
Gastroparesis
Refusal to eat intervention diet, food allergies or restrictions that the kitchen cannot accommodate, and/or dietary noncompliance with dietary energy needs

Treatment and study plan

Regular Diet

Other

Regular Diet

Ketogenic diet

Other

Ketogenic Diet

Primary outcomes

Assessment of positive and negative symptoms

Time frame: 3 months

Brief Psychiatric Rating Scale (BPRS): The BPRS scale will be the primary outcome measure. It will be administered at baseline and at the end of each week. The BPRS is considered the most widely used symptom rating scale in psychiatric research, is highly sensitive to change, and has excellent interrater reliability with appropriate training of raters. The BPRS assesses the level of 18 symptom constructs such as hostility, suspiciousness, hallucination, and grandiosity. The rater enters a number for each symptom construct that ranges from 1 (not present) to 7 (extremely severe). The score ranges from 18-126, with the higher the number the worse the symptoms.

Sponsors and collaborators

Lead sponsor

University of Maryland, Baltimore

Other

Registry information

Official study title

Single-Blind Randomized Ketogenic Diet vs. Control Diet in People With Schizophrenia

Important dates

Study start: 2023
Primary completion: 2026
Study completion: 2027
First posted: Aug 1, 2023
Registry last updated: Nov 12, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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