Spravato, known generically as esketamine nasal spray, is a prescription medication designed for specific mental health conditions. It is administered as a nasal spray in a supervised healthcare setting due to potential serious side effects like sedation and dissociation. This medication offers a different approach to treating severe depressive symptoms compared to traditional oral antidepressants.
What Spravato Treats
Spravato treats two forms of severe depression in adults. One is treatment-resistant depression (TRD), defined as major depressive disorder that has not improved after trials of at least two different antidepressant medications. The other is for depressive symptoms in adults with major depressive disorder (MDD) experiencing acute suicidal ideation or behavior. In both cases, Spravato is typically used in conjunction with an oral antidepressant, though it can be used as monotherapy for TRD.
When these symptoms are severe and include thoughts or actions related to suicide, it constitutes a psychiatric emergency. Spravato’s approval for these conditions addresses a need for faster-acting treatments given the typical four to six-week onset of effect for many conventional antidepressants.
How Effectiveness is Assessed
The effectiveness of Spravato is evaluated through clinical trials, using randomized, controlled study designs. These trials compare outcomes of patients receiving Spravato, often with an oral antidepressant, to those receiving a placebo or another active comparator. This helps isolate the medication’s specific effects.
A primary tool for measuring changes in depressive symptoms in these studies is the Montgomery-Åsberg Depression Rating Scale (MADRS). The MADRS is a clinician-rated scale that assesses the severity of ten common depressive symptoms, with total scores ranging from 0 to 60; higher scores indicate more severe depression. Researchers track changes in MADRS total scores from baseline to specific time points, such as 24 hours, four weeks, or longer.
A reduction in the MADRS score signifies improvement in depressive symptoms. For instance, a 50% or greater reduction from baseline in the MADRS total score is often defined as a “response” to treatment. “Remission” is typically defined as achieving a MADRS total score of 12 or less, indicating a significant alleviation of depressive symptoms. These standardized measures allow for consistent evaluation of treatment efficacy across different studies.
Clinical Trial Findings
Clinical trials have demonstrated Spravato’s efficacy in reducing depressive symptoms for both treatment-resistant depression and major depressive disorder with acute suicidal ideation or behavior. In studies for TRD, Spravato, when combined with an oral antidepressant, showed a greater improvement in MADRS scores compared to placebo plus an antidepressant. For example, some trials reported a decrease in MADRS total score ranging from -3.6 to -4.2 points more than placebo over four weeks.
The rapid onset of effect is a key finding, with significant reductions in depressive symptoms observed as early as 24 hours after the first dose in patients with MDD and acute suicidal ideation or behavior. In these studies, Spravato plus standard of care showed superiority over placebo plus standard of care in rapidly reducing symptoms. The MADRS score reductions at 24 hours were around -15.9 to -16.0 points for Spravato compared to -12.0 to -12.2 points for placebo, leading to mean differences of approximately -3.8 to -3.9 points favoring Spravato.
For TRD, studies have shown that a greater proportion of patients achieved remission with Spravato. In one study comparing esketamine nasal spray to quetiapine extended-release, both combined with an SSRI/SNRI, 27.1% of patients in the esketamine arm achieved remission by Week 8, compared to 17.6% in the quetiapine arm. Remission rates continued to increase over time, with 55% of esketamine patients achieving remission by Week 32 compared to 37% for quetiapine. In a trial supporting Spravato as monotherapy for TRD, 22.5% of patients achieved remission (MADRS total score ≤ 12) at Week 4, compared to 7.6% for placebo.
Considerations for Treatment Outcomes
Beyond the controlled environment of clinical trials, several factors influence an individual’s response to Spravato treatment. Adherence to the prescribed regimen is important, as Spravato is administered in a certified healthcare setting under direct observation. Patients typically receive doses twice weekly during the initial induction phase, then weekly, and eventually every other week for maintenance.
Concurrent use of an oral antidepressant is important for most patients receiving Spravato, particularly for MDD with acute suicidal ideation or behavior. This combination therapy provides comprehensive management of depressive symptoms. Patient characteristics, such as age and overall health, may also play a role in individual responses.
Ongoing monitoring by a healthcare provider is also a consideration for treatment outcomes. This includes regular assessment of depressive symptoms, blood pressure, and observation for potential side effects such as sedation or dissociation, which can occur after administration. The structured nature of Spravato treatment aims to manage these potential risks and promote positive outcomes.