Psychiatric Disorders

Medically supervised ketogenic diet as an adjunctive treatment for moderate to severe depression: A pilot study

Major depressive disorder is a prevalent and often treatment-resistant psychiatric condition, frequently co-occurring with metabolic dysfunction. Given growing interest in metabolic interventions, this pilot study explored the feasibility, safety, tolerability, and preliminary efficacy of a medically supervised ketogenic diet (MSKD) as an adjunctive treatment for moderate to severe depression.

The 14-week open-label, single-arm trial was conducted virtually through Kingston General Hospital in Canada. Eleven participants were enrolled, with eight completing both the induction and maintenance phases. All completers maintained nutritional ketosis, defined by blood β-hydroxybutyrate levels ≥ 0.5 mmol/L.

The intervention began with a two-week induction phase, progressing from moderate to high-fat intake and sharply reducing carbohydrates. This was followed by a 12-week maintenance phase supported by weekly consultations with a registered dietitian. Clinical assessments were conducted throughout, including the Montgomery-Åsberg Depression Rating Scale (MADRS), Generalized Anxiety Disorder-7 (GAD-7), and Snaith-Hamilton Pleasure Scale (SHAPS) to measure anhedonia.

Key Findings

Feasibility and Adherence:

• 73% (8/11) completed the full intervention
• All completers maintained nutritional ketosis, with 87.5% adhering continuously.
• Blood ketone levels averaged between 0.7 and 2.0 mmol/L across participants.

Depressive Symptoms (MADRS):

• Mean MADRS score decreased from 29.1 to 6.4 points.
• Average reduction of 23.3 points (p < 0.001).
• 87.5% of participants achieved remission (MADRS ≤10) by week 12.

Anxiety Symptoms (GAD-7): GAD-7 scores decreased by an average of 8.8 points (p = 0.005), indicating substantial improvement.

Anhedonia (SHAPS): SHAPS scores dropped from 5.4 to 0.6 (mean reduction: 4.8 points, p = 0.001), suggesting meaningful gains in hedonic capacity.

Safety and Tolerability: No serious adverse events were reported, with mild, transient side effects (e.g., gastrointestinal discomfort, headache, insomnia) mostly confined to the induction phase.

This pilot study demonstrates that a medically supervised ketogenic diet is feasible, well-tolerated, and associated with significant improvements in depressive symptoms, anxiety, and anhedonia in individuals with moderate to severe depression. These findings provide preliminary support for ketogenic therapy as a promising adjunctive intervention and warrant further investigation in larger randomized controlled trials.