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Exploring the Role of Dextromethorphan Depression Treatment: A Breakthrough Combination


Dextromethorphan depression treatment, commonly known as a cough suppressant, has taken an unexpected turn in recent years as a potential treatment for depression. This over-the-counter medication in popular cough syrups like Robitussin and Nyquil has been making waves in the mental health community. The combination of dextromethorphan with other antidepressants, such as bupropion, has shown promising results in relieving symptoms of depression. In this blog, we delve into recent research findings, the effectiveness of the combination treatment, potential side effects, and considerations for those exploring this unconventional approach to managing depression.

The Research:

Dextromethorphan’s journey from a cough suppressant to a depression treatment option began with initial research suggesting its efficacy. However, the real breakthrough came when it was combined with other drugs, showcasing even more promising results.

A 2020 study investigating the combination of dextromethorphan and memantine for individuals receiving treatment for bipolar disorder demonstrated a significant improvement in depressive symptom scores. This laid the groundwork for further exploration into the potential benefits of dextromethorphan in mental health.

In a phase 3 clinical trial conducted in 2022, researchers evaluated the effectiveness of dextromethorphan combined with bupropion (AXS-05) for treating major depressive disorder (MDD). The compelling results showed that this combination was more effective than a placebo in reducing MDD symptoms as early as the first week of treatment. After six weeks, over 39% of participants achieved remission compared to only 17.3% in the placebo group.

The Mechanism of Action:

One reason behind the efficacy of dextromethorphan for depression may lie in its impact on glutamate pathways. Moreover, a neurotransmitter believed to play a role in depression development. When combined with bupropion, a common antidepressant, this specific medication combination seems to address these pathways more effectively, providing relief for individuals struggling with depression.

Potential Concerns:

While the combination of dextromethorphan and bupropion shows promise. Therefore, it’s essential to acknowledge potential concerns. Some individuals may experience a temporary worsening of depression symptoms when initiating this treatment. Although a common occurrence with many antidepressants.

Research from 2017 suggests that high doses of dextromethorphan (over 1,500 mg a day) may lead to symptoms like delusions, hallucinations, and paranoia. However, there is currently no evidence to suggest a direct link between dextromethorphan and the onset or worsening of depression.

Side Effects:

Like any medication, dextromethorphan depression treatment can cause side effects. Commonly reported side effects include headaches, blurred vision, joint pain, dry mouth, dizziness, nausea, diarrhea, constipation, fatigue, lethargy, drowsiness, insomnia, anxiety, excessive sweating, sexual dysfunction, appetite changes, and tingling in the extremities.

In the phase 3 trial for dextromethorphan/bupropion, dizziness, nausea, headache, drowsiness. Furthermore, includes dry mouth were the most frequently reported side effects. Understanding these potential side effects is crucial for individuals considering this treatment option.

Cost and Coverage:

For individuals considering dextromethorphan-based medications like Auvelity, it’s important to factor in the cost. While most health insurance plans cover prescribed medications for specific conditions, coverage rules vary. It’s advisable to contact your insurance provider to understand the extent of coverage for newer options like dextromethorphan/bupropion.

Without insurance, these newer medications can be expensive, with estimates suggesting costs exceeding $560 for a 30-day supply of Auvelity. Understanding the financial aspect is crucial for individuals exploring long-term treatment options.


Dextromethorphan depression treatment, especially when combined with other antidepressants, represents a notable stride in mental health research. The positive outcomes from clinical trials provide hope for individuals living with major depressive disorder. However, it’s important to approach this unconventional treatment option with awareness of potential side effects and financial considerations.

If you are grappling with depression or a related mental health condition, reaching out to your doctor to discuss the viability of dextromethorphan-based treatments is a crucial step. The evolving landscape of mental health treatments continues to offer new possibilities, and for some, dextromethorphan may be a valuable addition to the toolkit of available therapies.

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