The U.S. Food and Drug Administration on Tuesday approved Spravato, a new nasal spray antidepressant using the drug esketamine, which works in a different way than any new drug approved for depression in decades.
The FDA has okayed esketamine for patients suffering from treatment-resistant depression who have tried at least two other antidepressants without relief. It is meant to be used in conjunction with an oral antidepressant.
Esketamine is the chemical mirror of ketamine, which has been used for years as an anesthetic but can be abused recreationally at higher doses. Recent studies have documented potent antidepressant actions of ketamine that take effect much faster than the two to four weeks of older medications.
“There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition,” said Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research.
“Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA’s drug approval process including a robust discussion with our external advisory committees, were important to our decision to approve this treatment. Because of safety concerns, the drug will only be available through a restricted distribution system and it must be administered in a certified medical office where the health care provider can monitor the patient.”
Some involved in the vetting and approval process expressed concern about side effects of esketamine, which is being developed by Janssen Pharmaceutical Companies, a division of Johnson & Johnson. These included increased risk of sedation, dissociation and higher blood pressure.
The FDA recommended implementing a risk evaluation and mitigation strategy (REMS) program which included making sure esketamine is only dispensed and administered under medical supervision.
Janssen indicated that esketamine would be given twice a week during the first month of treatment, then reduced to once a week or once every other week during the maintenance phase. There are still nagging questions about long-term treatment with esketamine, including how long to keep patients on the medication and what the risks of long-term use might be.
“Ketamine is a nasty drug … should (J&J’s) drug get approved, I think a strong effort has to be given as part of REMS … so that patients really know what they are getting themselves into,” Dr. Steven Meisel, another advisory panel member, told Reuters.
Because of its fast-acting effects, esketamine is also being weighed as a treatment for major depressive disorder with imminent risk for suicide, for which it has received an FDA “breakthrough therapy” designation. That classification is meant to expedite the development and review of drugs to treat a serious condition, and preliminary clinical evidence indicates the drug may show substantial improvement over available treatments.
Major depressive disorder affects nearly 300 million people of all ages globally and is the leading cause of disability worldwide. Individuals with depression, including major depressive disorder, suffer from a serious, biologically based disease that has a significant negative impact on all aspects of life, including quality of life and function.
Although currently available antidepressants are effective for many patients, about one-third of patients do not respond to treatment and are thought to have treatment-resistant depression.