| Efficacy |
Which clinical groups may (or may not) benefit? Can/should clinicians recommend LC/KD as ‘off-label’ therapy, and if so when and when not? What are the clinical and medicolegal implications? How should clinicians respond to patients preferring LC/KD over other therapies? (potential risk if those with severe symptoms choose LC/KD in place of evidence-based therapies). Do LC/KD have inherent antidepressant, anxiolytic and/or mood stabilising effects, or are these secondary to weight loss, improved energy (and behavioural activation)? ‘Dose’: is ketosis required or is a non-ketotic low carbohydrate diet effective? Times to response, response rates, numbers needed to treat and numbers needed to harm for LC/KD compared with other therapies. Could LC/KD augment/replace other therapies? Long-term efficacy and efficacy in relapse prevention. Efficacy in individuals without obesity/metabolic syndrome/type 2 diabetes. Could LC/KD improve cognitive problems in mood disorders?
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| Adherence |
Strategies to aid LC/KD induction and maintenance (is this more challenging for individuals with mood disorders compared with those following LC/KD for obesity/type 2 diabetes but without a mood disorder?) Speed and severity of relapse on discontinuation (case reports suggest this may be rapid and significant). Managing mood instability if LC/KD adherence is intermittent.
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| Adverse effects |
Impact and management of induction symptoms. Restricted diet might exacerbate disordered eating. Weight loss likely: beneficial in people with obesity/metabolic syndrome but problematic if normal or low baseline BMI (and is this a contraindication if so?). Gut health: constipation, altered gut microbiota and gut metabolites with negative effects. Cardiovascular risk is uncertain: beneficial effect on inflammatory markers but variable effect on lipids.
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| Potential effects on pharmacotherapy |
A ketogenic diet may affect pharmacokinetics, for example lowering valproate levels, needing dose adjustment. Ketogenic diet-related diuresis may cause electrolyte changes, which could affect lithium levels and increase adverse effects. LC/KD often lowers blood pressure, weight and glucose levels – antihypertensive and diabetic medications will need to be adjusted or withdrawn.
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