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

Why was RAPID a priority for NIMH?

There is an urgent need for improved, faster-acting antidepressant treatments for severe depression, which can be life-threatening due to a heightened risk of suicide. Current antidepressant medications usually take a few weeks to work—and half of patients fail to respond fully. 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.

Studies showed that ketamine, previously used as an anesthetic drug, can lift depression in many patients within hours. Researchers have made significant progress in pinpointing its mechanism of action and in identifying biomarkers that predict response. However, more research was needed to determine how ketamine can most effectively treat depression.

What was the impact of RAPID?

NIMH’s Intramural Research Program researchers pioneered studies of fast-acting antidepressant mechanisms in trials of ketamine and scopolamine. RAPID aimed to translate this evidence into practical treatments by evaluating interventions with proof-of-concept trials and then with randomized clinical trials for interventions that showed efficacy.

The RAPID team tested the optimal dosing of ketamine and the efficacy of treating depression with low-field magnetic stimulation, which uses a combination of low-strength, high-frequency electromagnetic field pulses to improve mood rapidly.

Study findings suggested that standard (0.5 mg/kg) and high doses (1 mg/kg) of ketamine can rapidly produce antidepressant effects, but lower doses are ineffective. RAPID researchers also found that 20-minute treatment sessions of low-field magnetic stimulation did not significantly improve symptoms for people with treatment-resistant depression. Additional work is needed to determine if more or longer treatments could be effective options.

The RAPID initiative deepened our understanding of the underlying mechanisms of depression and effective ways to quickly help patients who have not responded to currently available antidepressant medications.

Learn more about RAPID

Additional resources

• Depression Health Topic Page
• Depression Brochure

Science news and research highlights

• Experimental Medication Lifts Depression Symptoms in Bipolar Disorder Within an Hour
• Rapid Antidepressant Works by Boosting Brain’s Connections
• Millisecond Brain Signals Predict Response to Fast-Acting Antidepressant

Last Reviewed: January 2023