Spravato Approved for Treatment-Resistant Depression
March 5, 2019 – The U.S. FDA has approved Spravato™ (esketamine) CIII nasal spray, manufactured by Janssen Pharmaceuticals, for use in conjunction with an oral antidepressant to treat adults who have treatment-resistant depression (TRD).
An estimated one-third of patients with clinical depression, also known as major depressive disorder, have TRD. Clinical depression is a leading cause of disability in the United States, and is characterized by persistent symptoms that last for at least two weeks. These symptoms can include, but are not limited to, feelings of sadness, loss of interest, sleep disturbances, poor appetite, lack of energy, difficulty with memory and concentration, a sense of hopelessness, and recurrent thoughts of death or self-harm.
Spravato is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist – the first new mechanism of action approved to treat depression in decades. In clinical trials, it produced a statistically significant improvement in symptoms compared to placebo, with effects observed within two days of starting treatment. In addition, patients who achieved stable remission or a stable response and continued treatment with Spravato were 51% less likely to experience a relapse of depressive symptoms than patients on placebo. Due to the serious nature of TRD, all patients who participated in the trials were also treated with an oral antidepressant.
Recommended dosing with Spravato is one dose twice a week for the first four weeks. Patients are started at a 56mg dosage strength on the first day; the dosage strength can be increased to 84mg for subsequent administrations if needed. Beginning the fifth week, administration frequency is reduced to once per week. In the ninth week, it can be reduced to once every other week, depending on the patient’s response to treatment.
Although patients can self-administer Spravato, they must do so in an appropriate clinical setting, under the supervision of a qualified healthcare provider, as part of the drug’s Risk Evaluation and Mitigation Strategy (REMS). Patients must also remain at the site of administration for monitoring for at least two hours. The product is a Schedule III Controlled Substance related to ketamine, and can cause sedation and dissociation (difficulty with attention, judgment, and thinking). A black box warning advises of these risks, as well as the risk of misuse or abuse of the medication. It also cautions that Spravato is not approved for use in pediatric patients, and that there is an increased risk of thoughts of self-harm and suicidal behaviors in pediatric and young adult patients who are taking antidepressants. The black box warning recommends closely monitoring all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors.
Janssen has launched Spravato at a wholesale acquisition cost (WAC) of $4,720 to $6,785 for the first four weeks of treatment (the induction phase), and a monthly cost of $2,360 to $3,540 for maintenance treatment. Spravato will not be available for direct distribution to patients. It will only be available at certified treatment centers for supervised self-administration.
Spravato is currently the only FDA-approved form of esketamine. The related substance ketamine first received FDA approval in 1970 for use as an anesthetic agent.