PUSHING
BOUNDARIES
Medical Innovations:
There is New Hope in Novel Treatments for Difficult to Treat Mood Disorders
by John J. Wernert, MD
So much of our futuristic discussion around health care innovations seems to focus on new devices, artificial intelligence applications and virtual care. However, in clinical medicine, we must continue to heal with a“ personal” touch and must continue exploring new methods to treat“ body and brain” and promote holistic healing of disease. Mood disorders, especially depression, remain one of the most common conditions worldwide, affecting over 280 million people globally each year. Rates of mood and anxiety have risen consistently in adolescent and adult populations, especially since COVID-19, with the percentage of Americans being treated for depression growing annually since 2017. 1
New data from the CDC’ s National Center for Health Statistics indicate that the prevalence of depression in U. S. adolescents and adults increased 60 % in the past decade, representing 24 % of our population( 60 million people). Sadly, only 40 % of Americans affected obtained any treatment according to data from the National Health and Nutrition Examination Survey( NHANES). 2
Psychiatric care is not commonly associated with innovation as many brain-based conditions are elusive to study and hard to impact. However, the past five years have seen new disease modifying therapeutics in psychiatry, especially in altering the course of mood disorders. Hallucinogens, medical cannabis and brain stimulation have now become the new focus, speaking the language of the brain, using signal flow to alter neuronal signal propagation. 3
Antidepressant medicines are very commonly prescribed by primary care and various specialists, with marketing and direct to consumer advertising driving high rates of use. Standard antidepressant medications in conjunction with talk / psychotherapy have been accepted through research as the standard for depression treatment for years. Yet we who have prescribed medication and / or therapy understand that response rates are variable and remission for symptoms can be very elusive. The initial response rate for the first antidepressant is about 30 % with response rates decreasing with subsequent treatments. It has been evident for years that many factors play a role in poor antidepressant response, especially improper diagnoses, variable individual metabolism, medicine choices and the ubiquitous polypharmacy that befuddles providers. For over 50 years, newly marketed antidepressant therapies have been“ me too” drugs or spin-offs of existing medications. However, two novel therapies have been gaining acceptance in the past five years for relief of true treatment-resistant depression. I will review and compare these treatments, esketamine( Spravato) and Transcranial Magnetic Stimulation( TMS).
Esketamine is derived from ketamine, a well-known anesthetic. Esketamine is four times more potent in blocking the NMDA receptor and works differently from traditional antidepressants by increasing levels of glutamate, a neurotransmitter that plays a crucial role in brain function, rather than focusing solely on serotonin or norepinephrine. Esketamine’ s unique mechanism is thought to enhance synaptic connectivity and promote neuroplasticity. Unlike
10 LOUISVILLE MEDICINE