What is this research about?
Major depressive disorder, or depression, is a serious mental illness. It can lead to disruptions in relationships and work, disability, and even death. This project compares the effectiveness of two new treatments for depression: racemic ketamine delivered intravenously (IV ketamine) and esketamine delivered as a nasal spray. The type of depression that will be studied is called treatment-resistant depression. This is a type of depression where individuals do not experience benefit with standard oral antidepressants, such as fluoxetine, citalopram, or sertraline.
Because of its unique history, IV ketamine is unlikely to ever be approved by the US Food and Drug Administration (FDA) to treat depression. Esketamine, a similar but distinct treatment sponsored by Janssen Pharmaceuticals, did receive FDA approval. Hence, health insurance companies will often pay for it. Because only Janssen's esketamine holds the FDA indication, many health insurance companies limit their coverage to esketamine, not allowing the patients or providers to choose IV ketamine. However, there is a growing disagreement among experts as to how similar or different the two treatments are in relation to effectiveness and patient acceptability. Because there has never been a study directly comparing the two treatment approaches, no high-quality data is available to accurately inform the patients, providers, payers and policy makers on the true comparison of the treatments from the patient’s perspective.
Who can this research help?
This research could be helpful to a range of stakeholders. To ensure that the research addresses the broad range of interests and to maximize the impact of the findings, the study will be designed and executed with the advice of several different stakeholders. Stakeholders included in this project are patients (including those who have received one or both treatments to be studied), physicians (who prescribe and deliver the treatments), representatives from health insurance companies (who determine whether a health insurance policy will pay for a treatment), academic physician scientists (who analyze and disseminate the findings), and hospital and clinical administrators (who decide which treatments their clinics will offer).
This research could be helpful to all these stakeholders. It would help patients and physicians determine if one treatment is in fact more effective and acceptable. It could also help health insurance representatives determine their coverage policies on these treatment options and hospital and clinic administrators determine which treatments to offer.
What is the research team doing?
The research team will recruit individuals with depression who are seeking treatment with either IV ketamine or nasal esketamine. Those who agree to take part in the trial will be randomly assigned to either IV ketamine or nasal esketamine. This means that neither they nor the researchers can choose which treatment they will get. As individuals receive their assigned treatment (IV ketamine or nasal esketamine), they will give reports on their depression, anxiety and satisfaction with treatment. The researchers will also make careful observations related to the patient’s global improvement or worsening and the tolerability of the treatments during this time.
At the end of the study, the data will be used to help the research team decide if IV ketamine and nasal esketamine have similar antidepressant effects or if they are different. In total, about 400 patients will be enrolled in this study from six different sites. Each patient can be in the study for up to eight months. If the assigned treatment is not helpful, patients have the option to be treated with the other therapy. Patients will be asked to fill out questionnaires at one, three and six months after the treatment is completed.
The primary outcome to be studied will be the effectiveness of the treatment after four weeks (the standard course of IV ketamine or nasal esketamine). This will be measured by a 16-question survey called the Quick Inventory of Depressive Symptomatology. Patient acceptability and satisfaction is the second key outcome measure to be studied.
*All proposed projects, including requested budgets and project periods, are approved subject to a programmatic and budget review by PCORI staff and the negotiation of a formal award contract.