Major depressive disorder is the greatest cause of workplace disability, and depressive disorders are the world’s second greatest public health issue. During a presentation at NAMCP 2020 Virtual Spring Managed Care Forum, Michael E. Thase, MD, professor of psychiatry at the Perelman School of Medicine at the University of Pennsylvania, discussed treatment options for depressive disorders.
Diagnosing depressive disorders can be difficult due to the heterogeneity of key depressive symptoms, but screening tools are inexpensive and can be useful.
Over the past 20 years, three strategies have been developed to individualize care for these patients and improve treatment outcomes: measurement-based care, collaborative care, and shared decision-making. Measurement-based care consists of accurately assessing symptom severity, ensuring adequate antidepressant dosage, assessing tolerability of medication, and monitoring and promoting treatment adherence. Collaborative care involves nurses and other professionals to increase clinical contact and therapeutic support and ensure timely progression through algorithms, as well as the availability of psychologists and other clinicians to provide empirically validated psychotherapies. Shared decision-making moves away from a paternalistic relationship between the provider and patient and allows patients to make decisions with their physicians.
Despite various antidepressants, there remains an unmet need for treatment options. In clinical trials of first- and second-line antidepressants, there is an approximately 10% to 20% advantage of this treatment compared with placebo, thus there is limited specific efficacy. In addition, the adverse events associated with these drugs can be intolerable in up to 10% of patients, and they have a relatively slow onset of action.
Dr. Thase then discussed the antidepressant therapy algorithm, which begins with a first-line antidepressant (usually a generic selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor), followed by a switch to another first-line antidepressant. If another treatment change is warranted, combination and adjunctive strategies can be considered, as well as use of older antidepressants (e.g., tricyclic antidepressants or monoamine oxidase inhibitors). The next steps for treatment-resistant depression would include neuromodulation strategies (e.g., transcranial magnetic stimulation or electroconvulsive therapy), ketamine infusions, or intranasal esketamine, followed by vagus nerve stimulation or unproven/experimental strategies.
He then discussed the use of ketamine and esketamine in this patient population. An effective dose of ketamine is approximately 0.5 mg/kg infused over 40 minutes two to three times per week, with an antidepressant effect typically seen within three doses. This is not usually covered by insurance, and there are residual concerns about tolerance and long-term safety. However, increasing evidence has demonstrated a sustained benefit with weekly doses for months and years.
Esketamine is a more potent stereoisomer of racemic ketamine that is delivered intranasally, which is convenient for physicians and patients, he said. An 84 mg intranasal dose of esketamine is about equivalent to 0.5 mg/kg of intravenous racemic ketamine. In a 2019 study published in the American Journal of Psychiatry, use of esketamine plus an oral antidepressant improved response and remission rates compared with oral antidepressants and placebo. Long-term safety and abuse-resistance measures need to be considered.
Overall, novel therapies such as esketamine provide additional options for patients with treatment-resistant depression.
Presentation: Recent Developments in the Treatment of Major Depressive Disorder: Overcoming Barriers Through Personalized Care. NAMCP 2020 Virtual Spring Managed Care Forum, April 16-17.