For nearly thirty years, the FDA had not approved any new antidepressant medications since Prozac entered the market in 1988.
All that changed in March 2019, when the FDA approved Spravato, a nasal spray antidepressant for the treatment of adults with treatment-resistant depression, which is to be taken in conjunction with an oral antidepressant. Spravato is derived from esketamine and is the first FDA-approved medication of its kind. Esketamine is related to ketamine, an anesthetic and hallucinogenic more commonly associated with clubs, partygoers and highs. Ketamine had previously been used as an off-label treatment for depression in doses far below the amount used as a recreational drug.
Spravato was marketed as the answer to depression that did not respond to SSRI and SNRIs. In addition to its success treating depressive symptoms generally, manufacturer Johnson & Johnson also indicated that its clinical trials established that it works in hours rather than the weeks most antidepressants take to become effective.
Given Spravato’s relation to ketamine and its potentially serious side effects, the FDA has prohibited its administration at home. These side effects include sedation, dissociation, abuse and misuse, and suicidality. Patients must be monitored for two hours after administration to ensure that the patient has not developed any dangerous side effects and only then will be cleared to go home with another adult who can drive them home. The FDA has even given the medication a Boxed Warning, its highest warning level. Patients will be able to inhale the medication only at approved and certified treatment centers in low doses less likely to result in side effects.
In October 2019, Johnson & Johnson sought approval from the FDA for an additional indication — the treatment of adults with major depressive disorder with suicidal ideation with intent. The application is based upon findings from a recent clinical trial, the results of which were presented in September. The statistically significant clinical trial results included a reduction in depressive symptoms and severity of suicidality within 24 hours after the first dose of Spravato taken in conjunction with an oral antidepressant in comparison with those patients in the double-blind study who had received a placebo with an oral antidepressant.
Peter T. Crean, Esq.
Emma B. Glazer, Esq.
Although initial reports about Spravato appeared to be overwhelmingly positive, questions have since been raised about whether Johnson & Johnson rushed through the clinical trials for expedited FDA approval. Spravato was evaluated in three short-term clinical trials and one long-term (60 weeks) clinical trial. There is no clinical evidence that Spravato works beyond 60 weeks. In addition, reports indicate that six patients died during the clinical trial (three by suicide), but this was dismissed by the FDA. Johnson & Johnson dismissed the deaths by suicide as unrelated to the medication because severe depression is associated with suicidal behavior — even though suicidal patients were excluded from the clinical trial.
While the FDA’s approval of the first new major antidepressant is an exciting development in treatment of resistant depression, which affects more than 5 million Americans, psychiatrists would be wise to ensure that they hold detailed consent conversations with patients considering treatment with Spravato. In addition to the required written agreement between patient and physician regarding administration at a physician’s office, discharge after adequate monitoring, and travel home with another driver, additional precautionary measures should be considered, such as more frequent counseling or therapy to monitor suicidal thoughts or behaviors.
Peter T. Crean, Partner, and Emma B. Glazer, Associate, are attorneys in the Medical Malpractice Defense Group at Martin Clearwater & Bell LLP. For more information, visit mcblaw.com.