A Continued Evolution

Psychiatry continues to be one of the most dynamic and rapidly evolving specialties in medicine. Over the past decade, we have seen a whirlwind of innovation and advances: novel pharmacological agents, the rise of US Food and Drug Administration (FDA)–authorized prescription digital therapeutics (PDTs), the rapid pivot and adaptation to virtual care during the COVID-19 pandemic, and efforts to expand access to treatment by increasing the number of psychiatry residents, psychiatric mental health nurse practitioners, and psychiatric physician assistants. However, in my view, this progress has been hampered by the simultaneous transition of medicine from a patient-centric institution to a corporate/insurance-centric institution.

The good news is that, as the backbone of medicine, psychiatry is in a unique position to steer the continued evolution of medicine to a patient-centric culture. By working together and promoting a unified stance toward compassionate, responsible, ethical, accessible, and evidence-based health care delivery, we can ensure that innovations of today and tomorrow serve the needs of those who matter most: our patients.

A History of Innovations

To better understand where we are today, we need to reflect on our previous advances. I am fascinated by the fact that 3 of the most significant psychopharmacological advances in the past 10 years resulted from innovation and understanding the pharmacokinetic and pharmacodynamic properties of medications that have existed for decades (Figure). These advances have strengthened our pharmacological armamentarium with vesicular monoamine transporter type 2 inhibitors (deutetrabenazine and valbenazine), N-methyl-_D-aspartate–glutamate receptor antagonists (esketamine and dextromethorphan), and muscarinic cholinergic receptor 1 and 4 agonism (xanomeline) (Sidebar). The dedication of researchers to take agents, examine all their positive and adverse effects, and find ways to modify or combine with other agents is a wonderful example of innovation and patient-centric behaviors.

2024’s Novel Agent

The FDA approved the medication combination xanomeline/trospium (Cobenfy) in September 2024,¹ making it the first novel mechanism of action for the treatment of individuals with schizophrenia since the approval of chlorpromazine in 1954. Until this point, all agents since chlorpromazine were antagonists or antagonist/partial agonists of the dopamine-2 receptor, which is believed to be the mechanism that decreases psychotic symptoms.

Xanomeline/trospium, on the other hand, has no affinity to dopamine receptors.² Its mechanism is hypothesized to be secondary to xanomeline’s potent agonism at muscarinic cholinergic receptors 1 and 4, which are prominent in the brain’s prefrontal cortex and the ventral striatum, areas believed to be associated with positive, negative, and cognitive symptoms in schizophrenia. Xanomeline is believed to decrease presynaptic dopamine release in these 2 areas while having no effect on other dopamine tracts that are related to endocrine function and movement disorders.

The development of xanomeline/trospium is an example of innovation by an industry outsider that persevered against all odds and ultimately created a medication combination that has initiated a new paradigm in the understanding and treatment of schizophrenia and psychosis. For our patients to benefit, we must dedicate a significant amount of time to learn the neural circuitry involved, the pharmacokinetics and pharmacodynamics of xanomeline/trospium, how the brain’s muscarinic system differs from the dopamine system, and which patients may benefit from this novel medication. Medicine and especially psychiatry are young professions with rapidly emerging information that require ongoing education, including CME through many vehicles.

Prescription Digital Therapeutics

An exciting and rapidly growing technology is digital therapeutics, which are apps that augment or supplement traditional medical treatments. An advantage of these therapeutics is that they can be used when patients need them and are available wherever patients happen to be. Unlike the wide variety of apps available, these therapeutics have been well vetted by the FDA. Unfortunately, insurance reimbursement represents a huge obstacle to their access. Again, patient-centric treatments are marginalized by the insurance-centric health care system. In fact, Pear Therapeutics went bankrupt due to the lack of insurance coverage for their cognitive behavior therapy–based apps. The apps, reSET and reSET-O, which were designed for substance use disorders, were the first PDTs authorized by the FDA.

November 2024 saw a turn for the positive, as Medicare confirmed it would provide coverage for some mental health apps starting on January 1, 2025. Three new treatment/billing codes are being created “to describe these services and will monitor how digital mental health treatment devices are used as part of overall behavioral health care.”³

Although more than 20,000 mental health apps are available for download through the Apple App Store or Google Play Store, a very tiny subset—fewer than 10 apps—have been cleared by the FDA as PDTs (Table). To receive this clearance, PDTs are rigorously studied in randomized clinical trials and must demonstrate both efficacy and safety. If the FDA is satisfied with the data, they label the PDT as authorized (commonly referred to as cleared) as software as a medical device (SaMD). These PDTs then require a prescription from the patient’s licensed health care clinician. The SaMD can be used as complementary treatment to a medication or psychotherapy or used as the primary treatment, depending on how it was studied.

PDTs are a rapidly growing area of interest, especially as health care needs continue to exceed clinician availability. Most of the apps in the pipeline simply require a smartphone or tablet, making them readily accessible to a population ubiquitously using these devices and fluent with them. Of course, in order to prescribe PDTs, health care providers must learn how these PDTs operate, how they can be integrated into ongoing patient treatments, and how to educate their patients about their beneficial role in treatment.

Looking to 2025

Although we have made great strides in psychiatry this past decade, including this year, I am concerned that our patients may not be receiving the benefits of these treatments. Brief inpatient psychiatric admissions, poor communication of inpatient psychiatric providers with their outpatient counterparts, the commonly practiced 15-minute medication appointment, overbooked schedules, electronic documentation demands, returning calls to patients and pharmacies, prior authorizations, and exhaustion at the end of a long day of clinical practice converge to minimize the well-intentioned plans to educate ourselves about the enormous amount of new information and new treatments.

Curiously, the very institutions that exist to educate students in training—medical schools, residency programs, major medical centers, hospital systems, nursing schools, large treatment networks, nurse practitioner and physician assistant training programs—commonly insulate students from, rather than educate students about, the advances during the prior decade. For example, in speaking with clinicians around the country, I continue to be perplexed by the lack of knowledge of basic psychopharmacological tasks: how to perform an Abnormal Involuntary Movement Scale examination, how to differentiate the various movement disorders secondary to dopamine-2 receptor–blocking drugs, and how the treatment of these disorders varies dramatically among them.

What are you seeing? What are your frustrations and solutions? What must we consider during this continued evolution to keep us and the field patient-centric? As we look to the New Year, I welcome your ideas, recommendations, and perspectives based on your experiences of how well we are educating each other about novel treatments, and I will write a follow-up editorial to share your responses.

Dr Miller is Medical Director, Brain Health, Exeter, New Hampshire; Editor in Chief, Psychiatric Times; Staff Psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

References

1. Cobenfy. Prescribing information. Bristol Myers Squibb; 2024. Accessed November 11, 2024. https://packageinserts.bms.com/ppi/ppi_cobenfy.pdf

2. Miller JJ. Schizophrenia pharmacology: version 2.0. Psychiatric Times. 2024;41(11).

3. Calendar year 2025 Medicare Physician Fee Schedule final rule. Centers for Medicare & Medicaid Services. November 1, 2024. Accessed November 11, 2024. https://www.cms.gov/newsroom/fact-sheets/calendar-year-cy-2025-medicare-physician-fee-schedule-final-rule