The World Health Organization ranked depression as the leading cause of disability and the third-leading contributor to the global burden of disease. It even goes as far as to predict that the debilitating condition will be the top cause as soon as 2030. Cases of anxiety and depression increased by an astounding 25% in the first year of the COVID-19 pandemic alone, so it is imperative now more than ever to identify effective therapies for patients diagnosed with mental health conditions. A brand-new approval of a rapidly acting medication for the treatment of major depressive disorder (MDD) in adults is a hopeful advancement in antidepressive therapy.

With the estimates of the number of US adults who experience MDD reaching 21 million individuals, it is clear just how common a disorder it is. Since patients frequently first speak to their primary care physicians about symptoms of depression they may be experiencing, it is important for providers to be well-versed in the disorder's characteristics and be able to discuss treatment options to determine the appropriate approach. According to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), a major depressive episode is constituted by a period of at least two weeks where a patient has experienced five or more of the following symptoms, where one is either a depressed mood or decreased interest or pleasure in daily activities that they previously enjoyed:

• Depressed mood for most of the day
• Markedly diminished interest or pleasure in all or almost all activities for most of the day
• Significant (>5%) weight gain or loss or decreased or increased appetite
• Insomnia (often sleep-maintenance insomnia) or hypersomnia
• Psychomotor agitation or retardation observed by others (not self-reported)
• Fatigue or loss of energy
• Feelings of worthlessness or excessive or inappropriate guilt
• Diminished ability to think or concentrate or indecisiveness
• Recurrent thoughts of death or suicide, a suicide attempt, or a specific plan for committing suicide

Additional criteria to determine MDD are that the patient's symptoms are causing significant distress or functional impairment and that an episode is not attributable to the physiological effects of another medical condition (eg, thyroid or adrenal gland disorders, brain tumors, stroke, Parkinson disease, multiple sclerosis, AIDS) or use of certain drugs. Clinical evaluation should include checks of CBC and levels for electrolytes, TSH, B12, and folate. The Patient Health Questionnaire (PHQ-9) is a standard screening tool used as part of the dialogue with the patient to understand and scale the symptoms they are experiencing in order to help diagnose depression.

Despite MDD being a serious mental illness, it can be treated. Many patients have success with a combination of pharmacotherapy and psychotherapy. Individual patient response to pharmacotherapy can vary greatly, and full response time can take up to 12 weeks, though many do have improvement within one to two weeks. The recent FDA approval for Auvelity (bupropion HCl/dextromethorphan HBr) for the treatment of MDD in adults brings a new fast-acting pharmaceutical option for providers to offer. The drug, administered orally as extended-release tablets, is a unique combination of 45mg of dextromethorphan, an uncompetitive N-methyl D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist, and 105mg of bupropion, an aminoketone and CYP450 2D6 inhibitor. A differentiator of this new product is that it has the ability to work quickly in patients. Waiting for many weeks for an antidepressant to have a significant effect in patients can be challenging. The clinical trials for Auvelity demonstrated symptom improvement at week one and remission by week two. This markedly faster action may make this new addition a welcome treatment option. The drug is expected to launch in the fourth quarter of 2022.

The Auvelity prescribing label does carry a black box warning for the possible link of antidepressants to an increased risk of suicidal thoughts and behaviors in pediatric and young adult patients. The drug is not approved for use in children. All patients treated with antidepressants need to be monitored closely in order to identify any clinical worsening or development of suicidal thoughts and behaviors. Stay informed about emergent drug information, including treatment options for MDD, by updating or registering your profile to receive email alerts and other critical drug information updates from PDR. You can also stay current by using the official PDR app, mobilePDR, available for free from your favorite app stores.