A Ketogenic Diet for Treatment-Resistant Depression: A Randomized Clinical Trial

Area of Science:

• Nutritional Psychiatry
• Metabolic Interventions
• Mental Health Research

Background:

• Preclinical studies and case reports suggest ketogenic diets (KDs) may benefit depression.
• Robust evidence from randomized clinical trials (RCTs) for KD efficacy in depression is limited.
• Treatment-resistant depression (TRD) remains a significant clinical challenge with unmet therapeutic needs.

Purpose of the Study:

• To evaluate the efficacy of a KD compared to a control diet in adults diagnosed with TRD.
• To determine if a KD can significantly improve depressive symptoms in a TRD population.
• To assess the impact of a KD on various secondary outcomes related to mental health and functioning.

Main Methods:

• A randomized controlled trial (RCT) involving 88 adults (aged 18-65) with TRD was conducted.
• Participants were randomized 1:1 to a 6-week ketogenic diet (KD) or a control (phyto) diet, both with dietetic support.
• The primary outcome measure was the change in the 9-item Patient Health Questionnaire (PHQ-9) score from baseline to week 6.

Main Results:

• Both KD and control groups showed significant reductions in PHQ-9 scores.
• The KD group demonstrated a statistically significant, albeit modest, greater reduction in PHQ-9 scores at 6 weeks compared to the control group (mean difference -2.18, P=.05).
• No significant differences were observed between groups for secondary outcomes at 6 or 12 weeks, and no serious adverse events were reported.

Conclusions:

• A ketogenic diet (KD) exhibited antidepressant effects compared to a control diet at 6 weeks in adults with treatment-resistant depression (TRD).
• The clinical relevance of the observed benefits is uncertain due to modest effect sizes and lack of significant findings in secondary outcomes.
• Further research is needed to clarify the long-term efficacy and clinical utility of KDs for managing depression.