The U.S. Food and Drug Administration has approved Spravato (esketamine) CIII nasal spray for adults living with major depressive disorder who have had an inadequate response to at least two oral antidepressants, according to a news release issued by Johnson & Johnson.
Spravato is the first and only approved monotherapy for adults with refractory major depressive disorder. Approval of Spravato, granted following FDA priority review, was based on the results of a randomized, double-blind, multicenter, placebo-controlled trial. On day 28 of the trial, patients taking Spravato exhibited numerical improvements for all 10 items on the Montgomery-Asberg Depression Rating Scale (MADRS). After four weeks, 22.5 percent of patients taking Spravato achieved remission (score ≤12 on MADRS) compared with 7.6 percent of patients taking placebo.
Spravato nasal spray is administered by the patient under the supervision of a health care provider in a health care setting. Spravato targets the neurotransmitter glutamate; however, the mechanism by which esketamine exerts its antidepressant effect is unknown. In an effort to ensure the safe and appropriate use of Spravato, the medication is only available through a restricted program called the Spravato Risk Evaluation and Mitigation Strategy Program. This is due to the risks for serious adverse outcomes resulting from sedation, dissociation, respiratory depression, abuse, and misuse.
“Treatment-resistant depression can be very complicated, especially for patients who do not respond to oral antidepressants or cannot tolerate them. For too long, health care providers have had few options to offer patients much-needed symptom improvement,” Bill Martin, Ph.D., Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Innovative Medicine, said in a statement. “Spravato is now available as a standalone treatment, meaning patients may experience improvements in depressive symptoms as early as 24 hours and at 28 days — without the need for daily oral antidepressants.”
Approval of Spravato was granted to Johnson & Johnson.
What is the Montgomery-Asberg Depression Rating Scale (MADRS)?
The Montgomery-Asberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used by mental health professionals to measure the severity of depressive episodes in patients with mood disorders.
How does ketamine treat depression?
Unlike traditional antidepressants that target serotonin and norepinephrine, ketamine primarily works on the glutamatergic system, a different neurotransmitter pathway in the brain. Specifically, it blocks the N-methyl-D-aspartate (NMDA) receptor, a type of glutamate receptor. This action is believed to trigger a cascade of events that promote the growth of new synapses and neural connections in the brain, particularly in areas associated with mood regulation, like the prefrontal cortex. This neuroplasticity is thought to be crucial for its rapid antidepressant effects.
Scientists are exploring how ketamine influences other neurotransmitters and growth factors, contributing to its therapeutic benefits. While promising, ketamine is not a first-line treatment and is often considered for treatment-resistant depression.
How does treatment-resistant depression affect Black Americans?
Treatment-resistant depression (TRD) poses a significant challenge for Black people, often exacerbated by systemic inequities. While Black individuals may experience depression at similar rates to white individuals, they face unique barriers to effective treatment.
One key factor is misdiagnosis: Black individuals are more likely to report physical symptoms of depression, which may be overlooked or misinterpreted by healthcare providers unfamiliar with cultural nuances in symptom presentation. This can lead to inadequate treatment and the perception that depression is resistant to interventions.
Furthermore, socioeconomic disparities can limit access to quality mental healthcare. Lack of insurance, transportation, and culturally competent providers can hinder timely and appropriate treatment, contributing to TRD.
Experiences of racism and discrimination also play a role. These stressors can contribute to chronic depression and make it more difficult to respond to standard treatments. Additionally, historical mistrust of the healthcare system due to past injustices may lead to hesitancy in seeking help.