Potential risks and rewards of new treatments for depression, Parkinson's, colorectal cancer
May 1, 2019
Concern over a potential misuse of new depression medication
The U.S. Food and Drug Administration in March approved Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant, for the treatment of depression in adults who have tried other antidepressant medicines but failed to improve. These patients have what is called treatment-resistant depression.
While this new approach to depression may prove lifesaving in some cases, there is a very serious concern about misuse and abuse of this nasal spray. Because of the risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration, and the potential for abuse and misuse of the drug, it is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS).
“There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition,” said Dr. Tiffany Farchione, who is the acting director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research.
People with major depressive disorder who have tried at least two antidepressant treatments given at adequate doses for an adequate duration and still have not responded to treatment are considered to have treatment-resistant depression. The Spravato labeling contains a boxed warning that cautions that patients are at risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug.
Because of the risk of sedation and dissociation, patients must be monitored by a health care provider for at least two hours after receiving a dose of Spravato. The REMS requires the prescriber and the patient to both sign a Patient Enrollment Form that clearly states that the patient understands they should make arrangements to safely leave the health care setting to get home and that the patient should not drive or use heavy machinery for the rest of the day on which they received the drug.
The patient self-administers Spravato nasal spray under the supervision of a health care provider at a doctor’s office, and the spray cannot be taken home. Esketamine is the s-enantiomer of ketamine. Ketamine is a mixture of two enantiomers (mirror image molecules). This is the first FDA approval of esketamine for any use. The FDA approved ketamine (Ketalar) in 1970.
While it is the responsibility of physicians to provide a suicidal patient with the fullest range of effective interventions, in this case there is also a need to protect the public’s health by not promoting a new drug epidemic, according to experts in the field.
Gene therapy showing promise for Parkinson’s disease
Researchers now are testing gene therapy for treating Parkinson’s disease. A delicate operation that involves placing a gene into the brain has been found to reduce the severity of motor symptoms in patients with moderately advanced Parkinson’s disease. This approach is being tested in those patients who no longer can control their symptoms with medications.
In a phase I gene therapy trial led by University of California San Francisco, 15 patients were able to acquire up to three hours daily of extra “on-time”. This is the period in which their medication was effective without causing the involuntary muscle movements known as dyskinesia, a frequent side effect of longer-term medication use. Additionally, patients were able to decrease their Parkinson’s medication by up to 42 percent, depending on the amount of the brain that was infused and the dose of therapy.
“This is the first gene therapy trial for Parkinson’s disease in which intra-operative MRI-guided monitoring was used,” said study investigator Dr. Chad Christine, who is with the UCSF Department of Neurology and the Weill Institute for Neurosciences. “This allowed us to visualize and guide the infusion of the treatment into the brain in real time, to ensure delivery to the area that should provide maximum benefit.”
Dr. Christine said this approach may help patients to more efficiently convert levodopa into dopamine, thereby obtaining greater improvements in mobility with each dose. He said since many patients were able to substantially reduce the amount of Parkinson’s medications, this gene therapy treatment may also help patients by reducing dose-dependent side effects, such as sleepiness and nausea.
Vitamin D may help combat colorectal cancer
A new clinical trial is suggesting that supplementing chemotherapy with high doses of vitamin D may benefit patients with metastatic colorectal cancer by delaying progression of the disease. Scientists from Dana-Farber Cancer Institute recently reported very encouraging results from the SUNSHINE clinical trial, which included 139 patients with previously untreated metastatic colorectal cancer. These patients were randomly assigned to receive pills containing 4,000 international units (IU) of vitamin D per day along with standard chemotherapy or pills with 400 units (about the dose found in a multivitamin) along with chemotherapy.
“To our knowledge, this study is the first completed randomized clinical trial of vitamin D supplementation for treatment of advanced or metastatic colorectal cancer,” said Dr. Kimmie Ng, who is the director of Clinical Research in Dana-Farber’s Gastrointestinal Cancer Center, Boston, Massachusetts.
In the high-dose group, patients had a median delay of 13 months before their disease worsened. In the low-dose group, the median delay was 11 months. In addition, patients in the high-dose vitamin D group were 36 percent less likely to have disease progression or death during the follow-up period of 22.9 months.
“The results of our trial suggest an improved outcome for patients who received vitamin D supplementation, and we look forward to launching a larger trial to confirm these exciting and provocative findings,” said study senior author Dr. Charles Fuchs, who is the Director of Yale Cancer Center, New Haven, Connecticut.
Vitamin D, which is necessary for bone health, is made in the body through a chemical reaction dependent on sun exposure and is contained in some foods. In laboratory studies, vitamin D has demonstrated anti-cancer properties such as triggering programmed cell death, inhibiting cancer cell growth and reducing metastatic potential. Prospective observational studies have linked higher blood levels of vitamin D with a lower risk of colorectal cancer and improved survival of patients with the disease, but those studies could not prove that vitamin D was the cause.
The study and its findings are important because they identify a cost-effective, safe and easily accessible agent as a potential new treatment for metastatic colorectal cancer. “This could therefore potentially have a large and wide-reaching impact globally, regardless of a patient’s socioeconomic status or a country’s resources,” said Dr. Ng.
John Schieszer is an award-winning national journalist and radio and podcast broadcaster of The Medical Minute. He can be reached at firstname.lastname@example.org.