Spravato Approved for Treatment-Resistant Depression
Spravato, the esketamine nasal spray, was approved by the FDA for treatment-resistant depression as a monotherapy with no oral antidepressants required.
February 25, 2025
Spravato, the esketamine nasal spray approved in 2019 for use alongside oral antidepressants for treatment-resistant depression, has been approved by the U.S. Food and Drug Administration (FDA) as a standalone monotherapy with no oral medication required.
Esketamine is a form of the dissociative agent ketamine, commonly used as an anesthetic; it works by targeting the neurotransmitter glutamate. According to a randomized, double-blind, placebo-controlled study, 22.5% of patients who took Spravato alone for four months achieved remission from depression (as measured by MADRS) compared with 7.6% of patients taking placebo.1
Common side effects in clinical trials were disassociation, dizziness, nausea or vomiting, sedation, headache, decreased sensitivity, anxiety, increased blood pressure, and feeling of intoxication. Due to these potential risks, the treatment is available only through the Risk Evaluation and Mitigation Strategy Program and must be self-administered in certified health care settings. Spravato is approved for use in adults with major depressive disorder (MDD) who have had an inadequate response to two or more oral antidepressants.
Eight percent of Americans suffer from MDD, with far higher rates of prevalence found among people with ADHD. According to a decade-long study that looked at nearly 400,000 young adults with ADHD and an equal number of neurotypical young adults, approximately half of the ADHD group had a diagnosed depressive episode — more than twice the frequency seen in the non-ADHD group. The rate of attempted suicide was four times higher among the ADHD group than in the neurotypical control. 2
These findings echoed the results of an earlier study of people with mood disorders that found having comorbid ADHD was associated with a higher risk of suicide, more frequent hospitalizations, more recurrent episodes, and an earlier onset of depression.3
“MDD affects every aspect of a person’s life and makes it seem as though life is not worth living,” writes William Dodson, M.D., LF-APA, a psychiatrist specializing in adult ADHD, in his ADDitude article, “6 Unexpected Signs of Depression.” “The World Health Organization ranks depression as the single largest contributor to global disability.4 It’s a serious problem that needs to be addressed.”
Spravato may increase blood pressure and heart rate, a side effect also common with stimulant medications used to treat ADHD, like Adderall and Ritalin. Thus, taking both medications may increase risk of high blood pressure. This is one reason healthcare providers monitor patients’ heart rate and blood pressure in the two hours after medication is administered.
Treatment-Resistant Depression: Readers’ Experiences
About a third of individuals with depression find no relief from oral antidepressants.5 Consequently, millions of Americans who have tried multiple kinds of depression medication continue to struggle with symptoms like hopelessness and suicidality.
In recent years, a growing number of these individuals have sought relief through the monitored use of ketamine, a close relative of esketamine. FDA-approved as an anesthetic, ketamine must be used “off-label” to treat depression.
“I took ketamine for complex PTSD, depression, and suicidal ideation and it helped massively,” says Mia, an ADDitude reader in Texas.
Bob, a reader in Arizona explains that ketamine-assisted therapy helped him “immensely” with his depression: “My psychiatrist offered ketamine treatments for patients with treatment-resistant depression who likely would have checked themselves into a psychiatric hospital otherwise.”
Karlyn, in South Africa, credits ketamine treatments, recommended by her psychiatrist, with helping her through a period of acute suicidality when nothing else worked: “It was the best drug that I have ever used for the treatment of depression.”
Sources
1Janik A, Qiu X, Lane R, et al. SPRAVATO (esketamine nasal spray) as a monotherapy for treatment-resistant depression (TRD). American Society of Psychopharmacology Annual Meeting.; May 28-31, 2024. Poster W80.
2Babinski DE, Neely KA, Ba DM, Liu GL (2020) Depression and suicidal behavior in young adult men and women with ADHD: Evidence from claims data. Journal of Clinical Psychiatry, 81 (6) 7-13.
3Zhang, Z., Zhang, L., Zhang, G., Jin, J., & Zheng, Z. (2018). The effect of CBT and its modifications for relapse prevention in major depressive disorder: a systematic review and meta-analysis. BMC Psychiatry, 18. https://doi.org/10.1186/s12888-018-1610-5.
4Depression and Other Common Mental Disorders: Global Health Estimates. Geneva: World Health Organization; 2017, https://apps.who.int/iris/bitstream/handle/10665/254610/WHO-MSD-MER-2017.2-eng.pdf
5Zhdanava M, Pilon D, Ghelerter I, Chow W, Joshi K, Lefebvre P, Sheehan JJ. The Prevalence and National Burden of Treatment-Resistant Depression and Major Depressive Disorder in the United States. J Clin Psychiatry. 2021 Mar 16;82(2):20m13699. doi: 10.4088/JCP.20m13699. PMID: 33989464.
