What additional treatment should be considered for a 40-year-old male with major depressive disorder who is not responding to pharmacological (Pharmacal) therapy alone, according to American Psychiatric Association (APA) guidelines?

From the Guidelines

For a 40-year-old male with major depressive disorder not responding to pharmacotherapy alone, consideration of interventional treatments such as electroconvulsive therapy (ECT) or ketamine and esketamine is strongly recommended. According to the most recent guideline from the U.S. Department of Veterans Affairs and U.S. Department of Defense [ 1 ], these treatments are suggested for patients who have not responded to other treatments. Key points to consider include:

• The use of ketamine and esketamine in patients who have not responded to other treatments [ 1 ]
• Electroconvulsive therapy (ECT) is recommended in similar contexts, such as multiple prior treatment failures or need for rapid improvement [ 1 ]
• Psychedelic treatments are only recommended in a research setting [ 1 ]
• The guideline highlights the importance of considering interventional treatments and the use of psychedelic interventions, which have been extensively researched since the previous guidelines [ 1 ] Some important considerations for treatment include:
• The age of the evidence reviews, with the VA/DoD guideline having the most recent evidence review [ 1 ]
• The expansion of treatment options, including psychotherapy, ketamine, and esketamine, which increase choices for patients and providers [ 1 ]
• The need for additional research in areas such as psychedelic medications, pharmacogenomics, and treatment modalities [ 1 ]

From the Research

Treatment Options for Major Depressive Disorder

According to the APA guidelines, when a patient with major depressive disorder is not responding to pharmacal therapy alone, additional treatment should be considered. The following options can be explored:

• Augmenting the antidepressant with another therapy, such as atypical antipsychotics, buspirone, stimulants, thyroid hormone, or lithium 2
• Increasing the dose of the current antidepressant
• Switching to a different antidepressant
• Combining antidepressants

Non-Pharmacological Therapies

Non-pharmacological therapies, such as cognitive therapy and interpersonal psychotherapy, can also be effective in treating major depressive disorder:

• Cognitive therapy and interpersonal psychotherapy have been shown to have comparable effects in reducing depressive symptoms 3, 4
• Interpersonal psychotherapy focuses on addressing interpersonal problems and improving communication, expression of affect, and proactive engagement with the current interpersonal network 5
• Cognitive behavioral therapy can also be effective, but may have a higher dropout rate compared to interpersonal psychotherapy 4

Treatment-Resistant Depression

For patients with treatment-resistant depression, defined as inadequate response to ≥2 successive antidepressants in a single episode, alternative treatment strategies can be considered:

• Augmented antidepressant use can increase from first-line to third-line treatment 6
• Dual or triple antidepressant use can be considered, although this approach may not be effective for all patients 6
• Non-pharmacological therapies, such as cognitive therapy and interpersonal psychotherapy, can be used in conjunction with pharmacal therapy to improve treatment outcomes 3, 4, 5