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Personalized and Multimodal Treatment of MDD
Importance of Personalized and Multimodal Treatment: Key Insights From Recent Expert Presentations

Released: November 12, 2024

Expiration: November 11, 2025

Lisa Harding
Lisa Harding, MD
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Key Takeaways
  • Personalized and rapid treatment strategies: No single approach fits all. When managing major depressive disorder (MDD) and treatment-resistant depression (TRD), individualized treatment plans are essential. Adjust treatments based on the socioeconomic factors, clinical history, comorbidities, and overall health of the patient. 
  • Adjunctive/augmentation treatment options: For patients who do not achieve full remission with antidepressants alone, adding atypical antipsychotics can boost the efficacy of their current treatment. In addition to improving mood symptoms, addressing residual neurovegetative symptoms such as memory and concentration problems is crucial for full functional recovery in MDD.  
  • Nonoral pharmacologic/nonpharmacologic options: Nonpharmacologic therapies are a critical component of TRD management. Electroconvulsive therapy, transcranial magnetic stimulation, ketamine, esketamine, and vagus nerve stimulation are effective alternatives for patients who do not respond to medications alone.​ 

The management of major depressive disorder (MDD) and treatment-resistant depression (TRD) requires a careful balance of pharmacologic and nonpharmacologic interventions, especially as many patients fail to respond adequately to first-line treatments. During the past few months, leading experts in psychiatry have discussed evolving approaches. This commentary synthesizes key insights from these presentations, emphasizing the importance of personalized and multimodal treatment approaches. 

Personalized Treatment: The New Standard 
Experts have emphasized the importance of tailoring adjunctive therapies to the unique clinical profile of each patient, including prior treatment response and comorbid conditions. Personalizing treatment increases the likelihood of a successful outcome. Using guidelines in clinical practice is beneficial, as they provide a framework based on evidence and best practices. However, it is essential to understand their limitations. As healthcare professionals (HCPs), we cannot be so rigid in our adherence to guidelines that we risk undertreating patients. Individual patient needs, preferences, and responses to treatment must remain at the forefront of our decision-making, ensuring that we tailor our approaches to provide the best possible care. Balancing guideline adherence with personalized treatment is crucial for optimizing patient outcomes.

In patient care, it is crucial to aim for remission rather than settling for “good enough.” Although achieving some improvement in symptoms is a positive step, true recovery means striving for a state where patients can fully engage in their lives without the burden of persistent symptoms. Partial relief can leave individuals vulnerable to relapse and may inhibit their ability to thrive in various aspects of life, including work, relationships, and personal fulfillment. By committing to a goal of remission, we can empower patients to reclaim their well-being, enhance their quality of life, and promote long-term stability. It is our responsibility as HCPs to challenge the status quo and ensure that our patients receive the comprehensive care they need to achieve lasting recovery. 

Adjunctive/Augmentation Treatment Options
For patients who do not achieve full remission with antidepressants alone, adjunctive or augmentation treatment options can greatly enhance the effectiveness of their current therapy. Atypical antipsychotics are commonly used in MDD. These medications not only help improve mood symptoms but also address residual neurovegetative symptoms like memory, sleep, and concentration problems, which are crucial for achieving full functional recovery.

Here are 2 key clinical strategies to consider: 

  1. Switch antidepressants: If a patient has an inadequate response to their current treatment, switching to another antidepressant is a common approach. Bupropion, venlafaxine, or mirtazapine may offer improved outcomes, especially when the current treatment has led to intolerable adverse effects or suboptimal efficacy. For instance, bupropion is often chosen because of its lower risk of sexual adverse effects, whereas venlafaxine has shown efficacy in patients who do not respond to selective serotonin reuptake inhibitors. 
  2. Implement augmentation strategies: For patients who achieve a partial response to an antidepressant, augmentation is another viable option. Adding agents like lithium, atypical antipsychotics, or even thyroid hormone can enhance the effects of the existing antidepressant. This approach is particularly useful for those who have tolerated their current medication but need a stronger therapeutic effect. 

Although these strategies can improve treatment outcomes, HCPs must carefully weigh the benefits against potential risks, such as weight gain and metabolic syndrome. Continuous monitoring is essential for patients receiving these medications, especially over extended periods, to ensure a balanced and effective treatment approach. 

Nonpharmacologic treatments such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), and emerging treatments with ketamine and esketamine are key interventions for TRD. ECT remains one of the most effective treatments for severe depression, in particular for patients with psychotic features or at high risk of suicide. TMS and VNS offer alternatives with fewer cognitive adverse effects, making them suitable for patients who may be sensitive to the cognitive impairments associated with ECT. Ketamine and its nasal counterpart, esketamine, have garnered attention for their rapid-acting antidepressant effects, especially in cases where traditional therapies have failed. These treatments can provide relief within hours to days, representing an advancement in the management of TRD. Their unique mechanisms of action and potential for improving mood and overall functioning underscore the importance of considering a multimodal approach in treating depression, in particular for those who have not responded to standard pharmacologic interventions. 

Psychotherapy and adjunctive therapies such as cognitive-behavioral therapy and interpersonal therapy are often used alongside pharmacologic treatments to improve patient outcomes. In addition, therapies like bright light therapy and mindfulness can be effective, in particular in patients with seasonal exacerbations of depression​. 

Conclusion: A Multimodal Approach Is Key 
The consensus from recent discussions is clear: Managing MDD, particularly TRD, requires a personalized and multimodal approach. Whether through esketamine, atypical antipsychotics, TMS, or cognitive-enhancing treatments, combining multiple strategies offers the best chance for successful outcomes. As new treatment options emerge, HCPs are better equipped to help patients achieve not only mood improvement but full functional recovery. 

The exploration of adjunctive treatments for MDD has revealed opportunities to enhance patient outcomes, in particular for those who do not achieve full remission with standard antidepressants. As we integrate strategies like atypical antipsychotics, lithium, and nonpharmacologic interventions such as ECT, TMS, and ketamine, we are taking crucial steps toward more personalized and effective care. 

Looking ahead, there is a hopeful horizon in the field of psychiatry, with promising medications that target specific symptoms, such as anhedonia, on the verge of approval. Furthermore, the resurgence of interest in psychedelics as therapeutic agents offers exciting possibilities for treating depression and enhancing emotional well-being. These advancements not only provide optimism for those struggling with MDD but also signal a transformative era in psychiatry. As we continue to innovate and expand our treatment options, a future where every patient can find the relief and recovery they deserve, paving the way for brighter and more fulfilling lives. 

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