The FDA published draft guidance to assist developers of monotherapeutic, combination and adjunctive drug treatments for major depressive disorder, offering considerations for nonclinical safety and clinical pharmacology.

Sponsors should consider the drug’s intended treatment duration, its mechanism of action and all known pharmacodynamics and/or pharmacokinetic interactions with co-administered drugs, in addition to typical animal toxicology studies.

General toxicology studies should include a thorough evaluation of at least seven slices of the brain as described in Bolon et al.’s recommended practices for sampling and processing the nervous system during nonclinical general toxicity studies. Use of alternate slices can be justified based on the drug’s predicted sensitivity.