OBJECTIVES: Nutraceuticals or medical foods are used to address a specific dietary requirement necessary to treat a disease or condition. While they must be used under medical supervision, they are not regulated as drugs by the US FDA or EU EMA and do not require a prescription. However, medical foods do have the potential to be co-packaged for concomitant use as adjunctive therapy with prescription drugs for disease management. Our objective was to review current guidance documents provided by the FDA and EMA to identify necessary requirements for a medical food to enter the prescription pharmaceutical market as adjunctive therapy to treat depression.

METHODS: Depression-related clinical trial phase II and III requirements related to safety, efficacy, endpoints, study design, and study population were reviewed and summarized. FDA and EMA requirements were compared to identify key differences necessary for securing marketing authorization of a medical food as adjunctive therapy in the US and EU prescription pharmaceutical markets.

RESULTS: Efficacy is established through 2 adequate and well-controlled investigations and standard primary endpoints are clinician-rated outcome measures, while secondary endpoints assess other areas of symptom improvement in both the US and EU. Safety requirements should include pharmacokinetics-informed dosing and drug switching strategies in phase II and maintenance of a safety database in phase III in the US. Phase II trials should be randomized, double-blind, placebo controlled and last 6-8 weeks. Phase III should be randomized double-blind withdrawal trials and last at least 6 months. The study population should include DSM defined MDD patients and a range of severity in the US while EU studies should focus on moderate MDD.

CONCLUSIONS: Findings highlight the necessary evidence requirements to take a medical food to the prescription pharmaceutical market as adjunctive therapy in the treatment of depression, identifying differences between US FDA and EU EMA requirements.