DIETARY THERAPY

The ketogenic diet (KD) is a high‐fat, low‐carbohydrate, and adequate‐protein diet that mimics the fasting state by switching to fat as the primary energy source. KD has been used for the treatment of epilepsy since the 1920s, before the advent of the many conventional antiseizure medications (ASM).^1–3

KD therapy (KDT) has been used successfully in children with drug‐resistant epilepsy (DRE), and it is in this age group that the evidence base is strongest. KDT is a first‐line treatment for GLUT‐1 deficiency and pyruvate dehydrogenase deficiency (PDHD). Evidence suggests there is more than 50% seizure reduction in a third to a half of people when used in generalised epilepsies and symptomatic focal syndromes. Specific disorders in which KDT has been successfully used include infantile spasms, tuberous sclerosis, myoclonic‐atonic epilepsy, Dravet and Rett syndromes, absence seizures and complex 1 mitochondrial disorder. There is also limited data on efficacy in refractory status epilepticus, including FIRES and NORSE. Current thinking advocates for its earlier consideration in specific syndromes.^4–10

KDT may be a potentially effective intervention in adults with DRE in whom surgery has been excluded or declined, but evidence is lacking.^10–12 Discontinuation rates are high due to unpalatability and restrictiveness, which reduce adherence, particularly with the classical KD. Recently, relaxed variations have been developed to improve retention, including the Modified Atkins Diet (MAD), the Medium‐Chain Triglyceride (MCT) diet, and the Low‐Glycemic Index Treatment (LGIT). The different diets vary in the ratio of fat to carbohydrate (2 : 1 to 4 : 1) and the need to measure food portions.

Side effects of KDT include gastrointestinal symptoms such as constipation, nephrolithiasis, potentially adverse cardiovascular outcomes, muscle loss and vitamin, mineral and trace element deficiencies, reinforcing the need for regular monitoring. Long‐term outcome data are scarce, particularly in adults. Beyond the effect on seizures, there is some evidence to suggest that KDT may have potentially beneficial effects on cognition, well‐being and mood.¹³

KDT is also being explored in a range of disorders, from diabetes and obesity to cancer and neurodegeneration, and there is evidence that it may have epigenetic effects.¹⁴ The spectrum of its physiological and metabolic effects is likely to be wide‐ranging and requires elucidation. The biological basis through which the KDT suppresses seizures remains unknown; one proposed mechanism involves a role for decanoic acid in mitochondrial function. This, in turn, has led to some focus on using supplements of medium‐chain triglycerides (MCT) such as decanoic acid (C‐10) in epilepsy.^15–17 Research has also suggested that intermediary metabolites, including ketone bodies such as β‐hydroxybutyric acid, may augment GABA‐mediated neurotransmission.¹⁸

One obstacle is access to a dedicated KDT service. Such a service is essential for excluding contraindicating disorders (including liver failure, pancreatitis, fatty acid oxidation defects, carnitine cycle deficiencies, porphyria). They would also facilitate education and counselling before initiation, as well as monitoring and optimisation throughout treatment.

PSYCHOLOGICAL THERAPIES

Psychological approaches can improve well‐being, health‐related quality of life, enhance mood, reduce fatigue, facilitate medication adherence, and alleviate stress and anxiety. The rationale for pursuing such means for treating epilepsy is based on the idea that mental and behavioural states may influence seizure occurrence. There is an increased risk of depression and anxiety in people with epilepsy, with a bidirectional relationship between them. Acute stress is commonly cited as a seizure trigger.

Cognitive behavioural therapy (CBT), relaxation therapy, and biofeedback have been assessed; however, methodological deficiencies and small sample sizes are limiting factors in the interpretation of these studies. The current evidence base does not support the use of psychological interventions to treat seizures per se. However, the increased incidence of anxiety, low mood, and psychosocial difficulties in people with epilepsy means that psychologically‐based therapies form an essential part of comprehensive epilepsy care.^19–21