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A Randomised Controlled Trial Evaluating the Efficacy and Mechanisms of a Ketogenic Diet as an Adjunctive Treatment for People With Treatment-resistant Depression
In Brief
A clinical study evaluating Ketogenic Diet and Phytonutrient Diet for Treatment Resistant Depression and 4 related conditions. Completed, enrolled 88 participants across 1 site.
Detailed Summary
Depression is a debilitating chronic illness affecting 1 in 6 adults in the United Kingdom (UK) at any one time. Antidepressants and psychological therapy are the main treatments, but some people do not respond to these. Neurons and signals in the brain are greatly disrupted in people with severe depression. A ketogenic diet, a high-fat and very low-carbohydrate diet, supplies a form of energy that appears to help brain cells communicate and may improve the treatment of depression. Our goal is to find out whether a ketogenic diet could be an additional effective treatment for patients with depression for which antidepressants do not work. Using social media advertising, 100 patients, ages 18-65, who have previously tried at least two different antidepressant medications within the current depressive episode will be recruited. Enrolment, consent, and data collection will be collected online using self-report questionnaires. Participants will be allocated by minimisation 1:1 to the KD group or control group based on depressive severity (moderately severe vs. severe) and body mass index (\<30kg/m2 vs. 30+ kg/m2). The intervention group will receive 6-weeks of prepared ketogenic diet meals (3 meals with snacks per day) and weekly ketogenic diet-focused nutrition counselling. The control group will be asked to follow a diet to reduce their saturated fat intake and increase vegetable consumption by one portion a day. The control group will receive vouchers to assist with purchases and will be provided with weekly nutritional counselling. Existing treatment for depression will remain in both groups. The primary outcome is the change in depression symptoms at six weeks. All participants will complete assessments of depression and anxiety every two weeks, starting before treatment to post-intervention (week 6), and again at week 12. Additional outcomes include participants' ability to experience pleasure, quality of life, ability to socialise and work, cognitive processing, morning cortisol, and gut microbiome. At all stages of the study, adults with lived experience of depression will advise the research team to take into account the needs and views of patients. This study will provide evidence of whether following a ketogenic diet leads to a short-term improvement in depression in people whose depression cannot be relieved by antidepressants.
Study Details
Timeline
Interventions
A Ketogenic Diet (KD) is a high-fat and very low-carbohydrate intake. Participants will follow a modified KD (estimated 20-50g carbohydrates/day based on a 2000 kcal diet) without energy restriction. Participants will test for ketosis in their morning urine at least twice a week to monitor adherence. To support adherence in people with depression, delivered pre-prepared KD meals (3 meals per day) and additional ketogenic snacks will be sent to participants. A registered dietitian will provide weekly 30-minute nutritional counselling sessions. The dietitian will schedule appointments and assess the participants' experience with adhering to the KD diet, troubleshoot as required, give guidance on how to prevent or overcome side effects of KD diets, and keep record of participants' ketosis level and suicide risk.
Participants in the control group will receive the same degree of dietetic input and be told that their diet is a modified fat and phytonutrient diet. The photo diet aims to increase vegetable consumption, reduce saturated fat intake and increase poly- and mono-unsaturated fat intake. Participants in the control group will receive food vouchers (£20 every two weeks) to help purchase these items. This aims to be a plausible placebo dietary treatment for depression. There is no clear evidence that these manipulations will change depression severity. The dietitian will create written materials to explain the diet and suggest foods by colour with supporting recipe suggestions.