Ketogenic Diet and Neuromodulation for Depression

(ALIGN Trial)

This trial explores whether a ketogenic diet (a low-carb, high-fat eating plan) combined with a brain stimulation technique called iTBS (Accelerated Intermittent Theta Burst Stimulation) can reduce depression symptoms more effectively than iTBS with a standard healthy diet. It also examines adherence to the ketogenic diet during treatment and its effect on blood ketone levels. The trial seeks adults with moderate to severe depression that hasn't improved with previous antidepressant treatments and who are new to brain stimulation therapies. Participants will follow either the ketogenic or a balanced diet for 12 weeks, with regular health check-ins.

As an unphased trial, this study provides a unique opportunity to explore innovative treatment combinations for depression.

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you use anticonvulsants, GABA agonists, or medications that reduce TMS efficacy. Benzodiazepines are allowed if the dose is less than 2 lorazepam equivalents.

Research has shown that the ketogenic diet (KD) may help people with depression that hasn't improved with other treatments. In one study, participants on a KD experienced a clear reduction in their depression symptoms over 10 to 12 weeks. Another review found that KDs generally improved the mood of people with depression. No major safety issues were reported, suggesting it is generally well-tolerated.

Accelerated intermittent theta burst stimulation (iTBS) is a type of brain stimulation approved by the FDA for treating depression. Studies have shown that iTBS works as well as other treatments and is just as safe. Reports confirm that it does not cause serious side effects.

Researchers are excited about exploring the ketogenic diet for depression because it offers a novel approach compared to standard treatments like antidepressants and psychotherapy. Unlike traditional options that mainly target neurotransmitter levels, the ketogenic diet aims to induce nutritional ketosis, which may influence brain energy metabolism and inflammation, potentially addressing underlying causes of depression. Additionally, the diet provides a non-pharmacological option, which could be appealing for individuals seeking alternatives to medication with fewer side effects. This innovative approach has the potential to offer a new pathway for managing depression symptoms.

Research has shown that a ketogenic diet, which participants in this trial may follow, might help reduce symptoms in people with treatment-resistant depression. One study found that participants who followed this diet experienced a 69% to 71% decrease in their depressive symptoms. The ketogenic diet induces a state called nutritional ketosis, where the body burns fat for energy instead of carbohydrates. Some early reports suggest that this diet can improve certain mental health conditions by affecting brain function. While more research is needed, these initial findings offer promise for those dealing with depression.⁶⁷⁸⁹