Table 4.
Ongoing clinical trials exploring the role of the KD in psychiatric disorders.
| Identifier | Study Title | Status | Locations | Conditions | Hospitalized/ Amulatory Patients |
Age of Participants |
Enrollment | Intervention | Control | Timeframe | Primary Outcome and Timeframe |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03873922 [118] | Dietary Intervention for Psychotic Disorders: a Pilot Intervention Study of Ketogenic Diet for Psychotic Symptoms—PsyDiet Pilot Study | Recruiting | Kuopio, Finland | Patients with psychotic symptoms (ICD-10 diagnosis F20-29) | Hospitalized | ≥18 | 40 | Ketogenic diet (15–20 g CHO/d) | Conventional hospital meals | 6 weeks | Changes in PANSS and diet feasibility |
| NCT05968638 [119] | Single-Blind Randomized Ketogenic Diet vs. Control Diet in People With Schizophrenia | Recruiting | Catonsville, Maryland, United States | Schizophrenia/Schizoaffective disorder (DSM-IV/DSM-5) | N/A | 18–64 | 50 | Ketogenic diet | Standard diet | 3 months | Changes in BPRS |
| NCT05268809 [120] | Can Neural Network Instability in Schizophrenia be Improved With a Very Low Carbohydrate Ketogenic Diet? | Recruiting | San Francisco, California, United States | Schizophrenia/Schizoaffective disorder/Bipolar disorder (SCID-5) | Ambulatory | 18–65 | 70 | Ketogenic diet (70% F; 10% CHO; 20% PRO); 3 meals + snak/d | The diet as usual | 4 weeks | Changes in network stabilization, cognition, waist to hip ratio, HOMA-IR, blood: CRP |
| NCT06221852 [121] | A Randomized Controlled Clinical Trial of Ketogenic and Nutritional Interventions for Brain Energy Metabolism and Psychiatric Symptoms in First Episode Bipolar Disorder | Not yet recruiting | Belmont, Massachusetts, United States | Bipolar disorder/Schizoaffective disorder, onset of illness in the last 7 years (DSM-5) | N/A | 18–45 | 50 | Ketogenic diet (75–80% F; 7% CHO; 13–18% PRO); 3 meals + snak/d; normocaloric | Dietary Guidelines for Americans; 3 meals + snak/d; normocaloric | 12 weeks | Changes in PANSS, HAM-D, YMRS, CGI, insulin resistance, brain NAD+/NADH ratio and creatine kinase forward reaction rate |
| NCT06081426 [122] | Elucidating Neurobiological Mechanisms Underlying the Therapeutic Effect of the Ketogenic Diet in Bipolar Disorder (BD): a Multidisciplinary Mechanistic Study | Recruiting | Pittsburgh, Pennsylvania, United States | Bipolar disorder I/Bipolar disorder II, hypomanic/euthymic (DSM-5) | N/A | 18–30 | 107 | Ketogenic diet | Non-ketogenic diet/No diet | 8–10 weeks | Changes in YMRS, brain activity and connectivity, brain concentration of GABA, glutamate, lactate, blood: glucose, lipids, bilirubin, total protein, albumin, liver enzymes |
| NCT05705063 [123] | Impact of A Low-Carbohydrate, High-Fat, Ketogenic Diet on Obesity, Metabolic Abnormalities, and Psychiatric Symptoms on Patients With Bipolar Disorder (BPD) | Not yet recruiting | Stanford, California, United States | Bipolar disorder (DSM-5) | N/A | 18–75 | 30 | Ketogenic diet | No control group | 6 weeks | Changes in weight, waist circumference, visceral fat mass, body fat mass, heart rate, blood pressure, HOMA-IR, blood: HbA1c, hs-CRP, lipids |
| NCT06105762 [124] | KETO-MOOD: Ketogenic Diet for Microbiome Optimization and Overcoming Depression | Not yet recruiting | Basel, Switzerland | Major Depressive Disorder/Bipolar Depression (ICD-10/ICD-11) | N/A | 18–70 | 120 | Ketogenic diet (MAD, <20 g CHO/d) | Mixed diet following the recommendations for healthy nutrition by the Schweizerische Gesellschaft für Ernährung (Société Suisse de Nutrition) (45–60% CHO) | 8 weeks | Changes in HAM-D17 |
| NCT05558995 [85] | Effects and Mechanistic Aspects of Ketogenic Diet in Individuals With Major Depressive Disorder: A Pilot Study | Recruiting | Kingston, Ontario, Canada | Major Depressive Disorder (DSM-5) | Ambulatory | 18–55 | 10 | Ketogenic diet (20–30 g CHO/d; 80–100 g PRO/d; PUFA; MUFA) + vitamins, minerals in caps | No control group | 12 weeks | Adherence to diet |
| NCT06091163 [125] | A Randomised Controlled Trial Evaluating the Efficacy and Mechanisms of a Ketogenic Diet as an Adjunctive Treatment for People With Treatment-resistant Depression | Recruiting | Oxford, United Kingdom | Depression | Ambulatory | 18–65 | 100 | Ketogenic diet (20–50 g CHO estimated on a 2000 kcal/d); 3 meals + snacks | Modified fat and phytonutrient diet | 6 weeks | Changes in PHQ-9 |
| NCT06080932 [126] | Ketogenic Intervention in Depression | Recruiting | Columbus, Ohio, United States | Major Depressive Disorder (DSM-5) | Ambulatory | 18–30 | 30 | Ketogenic diet (<50 g CHO/d, ~1.5 g PRO/kg reference weight) | No control group | ~up to 12 weeks | Changes in HAM-D17, WHO-5, blood: ketones and glucose |
DSM—Diagnostic and Statistical Manual of Mental Disorders; ICD—International Classification of Diseases; SCID—The Structured Clinical Interview for DSM; N/A—Not Applicable; CHO—carbohydrates; PRO—protein; PANSS—The Positive and Negative Syndrome Scale; BPRS—The Brief Psychiatric Rating Scale; HAM-D—Hamilton Depression Rating Scale; YMRS—Young Mania Rating Scale; PHQ—Patient Health Questionnaire; CGI—The Clinical Global Impressions Scale; WHO-5—The World Health Organisation-Five Well-Being Index; HOMA-IR—Homeostatic Model Assessment for Insulin Resistance; HbA1c—Glycated hemoglobin; CRP—C-Reactive Protein; GABA—Gamma Amino Butyric Acid; NAD/NADH—the ratio of oxidized and reduced forms of nicotinamide adenine dinucleotide.