Pharmacy and Wellness Review
Abstract
Treatment-resistant depression (TRD) is a challenging and possibly life-threatening condition that affects millions of people worldwide. Patients with major depressive disorder (MDD) are diagnosed with TRD once they have tried and failed to respond to two antidepressant treatments at the maximum dose for a full trial of six to eight weeks. Most traditional antidepressant therapies work by increasing the levels of monoamine neurotransmitters such as dopamine, serotonin, and norepinephrine in the brain. These medications have a delayed onset of action, ranging from two to eight weeks, and often fail to relieve depressive symptoms in a patient with TRD. Therefore, targeting alternative neurotransmitters is crucial when developing treatments for TRD. Esketamine, the active component of Spravato®, primarily targets the major excitatory neurotransmitter glutamate and is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. It is formulated as a nasal spray, allowing for rapid absorption of the medication which leads to a faster onset. It has previously been utilized as an adjunct therapy to traditional antidepressants to help relieve patients of their depressive symptoms. However, Spravato® was recently FDA-approved in 2025 as monotherapy for adults with TRD. In clinical trials, Spravato® showed statistically significant improvement of depressive symptoms and indicated that it is safe to use as monotherapy to treat TRD. Although Spravato® has shown to be an effective agent in the treatment of TRD, it is associated with many adverse effects, including an increase in blood pressure, sedation, dissociation, and potential for abuse. Spravato® is available for use via the Risk Evaluation and Mitigation Strategy (REMS) program and thus must also be monitored closely during administration by a health professional. Despite the challenges associated with the use of Spravato®, it is at the forefront of bringing relief to patients suffering from TRD. Importantly, pharmacists can play a critical role in monitoring and educating patients using Spravato to ensure optimal outcomes in patients suffering from TRD.s1
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Pharmaceutical Preparations Commons, Psychiatric and Mental Health Commons, Psychiatry Commons