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Rapidly-Acting Treatments for Treatment-Resistant Depression (RAPID)

Rapidly-Acting Treatments for Treatment-Resistant Depression (RAPID) is an NIMH-funded research project that promotes development of speedier therapies for severe, treatment-resistant depression. The initiative is supporting a team of researchers, led by Maurizio Fava , M.D., of Massachusetts General Hospital, who are identifying and testing promising pharmacological and/or non-pharmacological treatments that lift depression within a few days.

By contrast, current antidepressant medications usually take a few weeks to work – and half of patients fail to fully respond. While a proven brain stimulation technique, electroconvulsive therapy (ECT), works faster, it runs a risk of cognitive side-effects and requires anesthesia and a surgical setting. The urgent need for improved, faster acting antidepressant treatments is underscored by the fact that severe depression can be life-threatening, due to heightened risk of suicide. 

Recent studies have shown that ketamine, a drug known previously as an anesthetic, can lift depression in many patients within hours. Researchers are making significant progress in pinpointing its mechanism of action and in identifying biomarkers that predict response.

It’s unlikely that ketamine itself will become a practical treatment for most cases of depression. It must be administered through infusion, requiring a hospital setting, and can potentially trigger adverse side effects. Patients also typically relapse after treatment ends. But such research provides clues to potentially discoverable fast-acting antidepressant brain mechanisms, and the RAPID team is collaborating with investigators in NIMH’s Intramural Research Program , who have pioneered studies of fast-acting antidepressant mechanisms in trials of ketamine and scopolamine. The project aims to translate such evidence into practical treatments by evaluating interventions that show efficacy in proof of concept trials in humans, and following up, if warranted, with randomized clinical trials.

The RAPID team, which incorporates several research sites, is planning to test new compounds that work through the same brain mechanisms as ketamine, as well as non-pharmacological treatments such as magnetic brain stimulation therapies. Through this research, we will enhance our understanding of the underlying mechanisms of depression and guide the development of new ways to quickly help patients who have not responded to current antidepressant medications.