The US Food and Drug Administration (FDA) is revising its guidance on the clinical development of treatments for major depressive disorder (MDD).
FDA says the guidance—being issued today in draft form—contains major revisions to its 1977 Guidelines for the Clinical Evaluation of Antidepressant Drugs.
The recommendations made in the eight-page guidance apply to monotherapeutic, combination and adjunctive treatments for MDD, a common mood disorder characterized by persistent feeling of sadness or anxiety. FDA notes that its recommendations do not apply to the development of drugs to treat bipolar depression or to nonpharmacologic therapies.
FDA says that the regulatory issues for a particular drug development program will depend on whether the indication being pursued is for short- or long-term use.
The agency also notes that clinical trial design and regulatory issues may differ for rapid-acting antidepressant drugs, which are currently in development.
For maintenance treatments, FDA says it is interested in seeing studies that test whether responses can be maintained with a lower dose of the drug than is required for short-term efficacy and would consider adding the results of such studies to a product's label.
Overall, the guidance has been modernized to include more up-to-date evaluations, study designs, trial endpoints and diagnosis tools.
For instance, FDA says it has accepted the Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale and Children's Depression Rating Scale as primary endpoints for Phase 3 studies, but notes that novel endpoints may be acceptable.
The guidance also provides recommendations for statistical considerations, the collection of long-term safety data and recommendations for special populations, including pregnant women and children.
FDA says that sponsors should try to include patients with other conditions, including renal insufficiency, cardiac disease, chronic pain and hepatic impairment in their studies, and that patients with HIV and hepatitis C should not be excluded.
Additionally, FDA says that sponsors looking to include a biomarker as a facet of their development program should request a meeting with its Division of Psychiatry Products early on, as there are no currently recognized surrogate markers for assessing antidepressant effectiveness.
FDA, Federal Register Notice