conventional antidepressants that may take weeks to show effects, esketamine can provide relief from depressive symptoms within hours. Speed of onset is a major selling point for struggling patients. This rapid action is particularly beneficial for patients who have not responded to multiple antidepressant treatments.
Esketamine was initially studied with an oral antidepressant but is now indicated for monotherapy. 4 Spravato( esketamine) is delivered in a clinical office on an outpatient basis, typically receiving three doses of intranasal sprays spaced five minutes apart. Since esketamine has the potential to distort perception, the patients are monitored in-clinic for two hours and are not allowed to drive themselves home. Our clinic starts therapy with twice weekly treatments for four weeks then begin gradual taper of the frequency to eventually a maintenance phase( monthly). Providers must be certified in the FDA REMS program( Risk Evaluation and Mitigation Strategy); regular reports must be submitted after treatments.
U. S. suicide rates remain alarmingly high, with 50,000 deaths by suicide annually, making it the eleventh leading cause of death overall. Conventional antidepressants may actually increase suicidal thoughts, especially SSRIs. 5 Only esketamine and lithium have been proven to decrease suicidal thoughts.
While esketamine is effective, it is not without risks. Patients may experience side effects such as sedation, dissociation and uncomfortable intoxication. Due to these risks, esketamine is only available through a restricted distribution program, and should not be used in patients with a history of mania, substance abuse or cardiovascular disease. Its rapid action and unique mechanism make it a valuable option for many patients struggling with severe depression.
Transcortical Magnetic Stimulation( TMS) is another novel treatment for patients showing poor response to oral antidepressant medications. This technology uses a coil to produce magnetic pulse waves that stimulate the bilateral prefrontal cortex, with a preference for the left dorsolateral prefrontal cortex. TMS is the only brain stimulation tool that does not use electricity directly but rather delivers magnetic pulses that induce focal depolarization of underlying neurons. Clinical data in real life practice settings have shown compelling results. Among patients who have completed 30 or more sessions, four out of five achieved a clinical response and approximately two-thirds achieved remission from depression. Benefits appear most profound for Major Depressive Disorder( MDD), Late-life depression, Anxious Depression and Obsessive-Compulsive Disorder( OCD). 6
This is a non-invasive, prescription-only procedure, and is performed while the patient is awake. By stimulating these specific nerve cells, TMS can restore activity in underactive areas of the brain, potentially improving mood and other symptoms. 7 The treatments are typically administered five days a week for about six weeks with each session lasting between 30-60 minutes.
Advantages over long established treatments such as electro-convulsive therapy( ECT) include a non-invasive, non-traumatic procedure that does not require anesthesia. Patients are awake during the treatment and can immediately return to their normal daily activities, including driving. Memory loss and rates of induced seizures are also lower. 8 Negatives include challenging insurance approval and out-ofpocket costs. In addition, TMS has a lower response rate compared to ECT for severe depression( 60 % vs. 80 %) and treatment-resistant depression( 50 % vs. 70 %). 9
In comparing esketamine and TMS therapies, several distinctions emerge. While TMS requires 30-36 treatments over six weeks, the benefits are sustained. Spravato works much more rapidly( within hours / days) but requires maintenance treatments. TMS is also less invasive, and patients can return to normal activities immediately versus esketamine which requires longer monitoring and no driving afterwards.
Both are covered by insurance for eligible conditions; however, documentation and prior authorization can be a real challenge.
In summary, both esketamine and TMS represent significant advancements in the treatment of depression, particularly for those who have not found relief through traditional therapies. For the first time in 60 years, we now have studied, and FDA approved antidepressant therapies that aren’ t just spinoffs of existing drugs. Though oral antidepressants will remain a frequent( and inexpensive) go-to for most providers, it is exciting to know that new treatments are available where none existed before.
References
1 https:// www. NAMI. org – National Alliance on Mental Illness
2 https:// www. cdc. gov / nchs
3
Psychiatric News, Nov 2025, Brown et al
4 https:// jamanetwork. com / journals / jama / article-abstract / 2837026
5 https:// www. cdc. gov
6
Am J Psychiatry 2025; 182( 3): 240-242
7 https:// www. yalemedicine. org
8
PubMed, Steinholtz et al, J. Affective Disorder, 2021
9
JAMA Netw Open, 2022, Jun 23: 5( 6)
Dr. Wernert is the Executive Medical Director of Norton Medical Group and practices with Norton Behavioral Medicine.
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