A 6-week ketogenic diet in treatment-resistant depression: a prospective single-arm feasibility pilot trial.
Prior evidence for the ketogenic diet (KD) interventions in treatment-resistant depression (TRD) was very limited when recruitment for the present pilot trial began on 1 November 2023. This pilot trial aimed to examine feasibility, adherence, safety, and preliminary clinical signals in patients with TRD treated with a 6-week KD intervention.
This prospective, single-arm, open-label pilot trial was conducted in adult patients with TRD who had a baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 20. The intervention consisted of a 6-week KD; preexisting psychopharmacological treatment had to be stable before study entry and was not changed during the intervention. Adherence was monitored by daily fasting capillary β-hydroxybutyrate measurements. The MADRS was assessed at baseline and after 2, 4, and 6 weeks in all participants. A response was defined as a ≥ 50% reduction in the MADRS score from baseline; remission was defined as a MADRS score of ≤10.
A total of 13 eligible patients were offered study participation; 5 declined, and 8 were enrolled. Four patients completed the full 6-week intervention. One patient discontinued after week 2, one patient was excluded after a revised diagnosis, and two patients discontinued because nutritional ketosis was not achieved. Nutritional ketosis was documented in all completers and was accompanied by marked symptomatic improvement in three of the four completers. Among the completers, two patients met the remission criteria at week 6, whereas one showed partial improvement and one showed no relevant antidepressant benefit despite sustained nutritional ketosis. The intervention was generally feasible, but recruitment and retention were challenging.
In this small prospective pilot trial, a KD was feasible in a subset of patients with TRD and was associated with improvement in depressive symptoms in three of the four completers. However, recruitment difficulties, early discontinuations, and heterogeneity of clinical responses highlight the need for larger controlled studies.
This prospective, single-arm, open-label pilot trial was conducted in adult patients with TRD who had a baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 20. The intervention consisted of a 6-week KD; preexisting psychopharmacological treatment had to be stable before study entry and was not changed during the intervention. Adherence was monitored by daily fasting capillary β-hydroxybutyrate measurements. The MADRS was assessed at baseline and after 2, 4, and 6 weeks in all participants. A response was defined as a ≥ 50% reduction in the MADRS score from baseline; remission was defined as a MADRS score of ≤10.
A total of 13 eligible patients were offered study participation; 5 declined, and 8 were enrolled. Four patients completed the full 6-week intervention. One patient discontinued after week 2, one patient was excluded after a revised diagnosis, and two patients discontinued because nutritional ketosis was not achieved. Nutritional ketosis was documented in all completers and was accompanied by marked symptomatic improvement in three of the four completers. Among the completers, two patients met the remission criteria at week 6, whereas one showed partial improvement and one showed no relevant antidepressant benefit despite sustained nutritional ketosis. The intervention was generally feasible, but recruitment and retention were challenging.
In this small prospective pilot trial, a KD was feasible in a subset of patients with TRD and was associated with improvement in depressive symptoms in three of the four completers. However, recruitment difficulties, early discontinuations, and heterogeneity of clinical responses highlight the need for larger controlled studies.