One-third of people with depression do not respond to antidepressants, and, after two adequate courses of antidepressants, are classified as having treatment-resistant depression (TRD). Some case reports suggest that ketogenic diets (KDs) may improve some mental illnesses, and preclinical data indicate that KDs can influence brain reward signalling, anhedonia, cortisol, and gut microbiome which are associated with depression. To date, no trials have examined the clinical effect of a KD on TRD. This is a proof-of-concept randomised controlled trial to investigate the efficacy of a six-week programme of weekly dietitian counselling plus provision of KD meals, compared with an intervention involving similar dietetic contact time and promoting a healthy diet with increased vegetable consumption and reduction in saturated fat, plus food vouchers to purchase healthier items. At 12 weeks we will assess whether participants have continued to follow the assigned diet. The primary outcome is the difference between groups in the change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to 6 weeks. PHQ-9 will be measured at weeks 2, 4, 6 and 12. The secondary outcomes are the differences between groups in the change in remission of depression, change in anxiety score, functioning ability, quality of life, cognitive performance, reward sensitivity, and anhedonia from baseline to 6 and 12 weeks. We will also assess whether changes in reward sensitivity, anhedonia, cortisol awakening response and gut microbiome may explain any changes in depression severity. This study will test whether a ketogenic diet is an effective intervention to reduce the severity of depression, anxiety and improve quality of life and functioning ability for people with treatment-resistant depression.

中文翻译：

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评估生酮饮食作为难治性抑郁症患者辅助治疗的功效和机制：随机对照试验方案


三分之一的抑郁症患者对抗抑郁药没有反应，在服用两个足够的抗抑郁药疗程后，被归类为难治性抑郁症 (TRD)。一些病例报告表明，生酮饮食（KD）可以改善一些精神疾病，临床前数据表明，KD 可以影响与抑郁症相关的大脑奖赏信号、快感缺乏、皮质醇和肠道微生物组。迄今为止，还没有试验检验 KD 对 TRD 的临床效果。这是一项概念验证随机对照试验，旨在调查为期六周的每周营养师咨询加上提供 KD 餐的计划的效果，与涉及类似饮食接触时间和通过增加蔬菜摄入量和促进健康饮食的干预措施进行比较。减少饱和脂肪，再加上食品券来购买更健康的物品。第 12 周时，我们将评估参与者是否继续遵循指定的饮食。主要结果是各组之间患者健康问卷 9 (PHQ-9) 评分从基线到 6 周的变化差异。 PHQ-9 将在第 2、4、6 和 12 周进行测量。次要结果是组间抑郁缓解变化、焦虑评分变化、功能能力、生活质量、认知表现、奖励敏感性、从基线到 6 周和 12 周的快感缺失。我们还将评估奖励敏感性、快感缺失、皮质醇觉醒反应和肠道微生物组的变化是否可以解释抑郁症严重程度的变化。这项研究将测试生酮饮食是否是一种有效的干预措施，可以降低难治性抑郁症患者抑郁、焦虑的严重程度，提高生活质量和功能能力。