Ketogenic Diet for Treatment-Resistant Depression: Dietary Interventions for MEntal Health Study (DIME)

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