Dextromethorphan in Fibromyalgia

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must not be taking: MAOI, Anti-inflammatories

Disqualifiers: Rheumatologic, Auto-immune, Blood disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

27 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using any anti-inflammatory medications like aspirin, ibuprofen, or naproxen. If you are currently using a MAOI (a type of antidepressant) or consuming grapefruit juice daily, you will also need to stop.

What data supports the effectiveness of the drug Dextromethorphan/Bupropion?

Dextromethorphan combined with bupropion, known as Auvelity, has been approved for treating major depressive disorder (MDD) in adults. Clinical trials have shown that this combination is effective in treating MDD by altering neurotransmission in the brain, which is linked to depression. ^{1 2 3 4 5}

Is dextromethorphan generally safe for humans?

Dextromethorphan has been used safely for over 30 years as a cough suppressant, with adverse reactions being infrequent and usually not severe. However, it can cause side effects like dizziness, nausea, and headaches, and there are safety concerns when mixed with certain other drugs or when abused. ^{1 2 3 6 7}

How is the drug dextromethorphan-bupropion unique for treating major depressive disorder?

Dextromethorphan-bupropion (Auvelity) is unique because it combines dextromethorphan, which acts on NMDA receptors and sigma-1 receptors, with bupropion, which increases the availability of dextromethorphan in the body. This combination offers a novel mechanism of action compared to traditional antidepressants, potentially providing faster relief from depression symptoms. ^{1 2 3 4 8}

What is the purpose of this trial?

This trial is testing if DXM, a common cough medicine ingredient, can reduce pain in people with Fibromyalgia by calming brain inflammation. If successful, it could offer a new way to manage this chronic condition.

Research Team

Jarred W Younger, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

Inclusion Criteria

Severe chronic fatigue ≥6 consecutive months not due to ongoing exertion or other medical condition associated with fatigue;

Daily self-reported pain of at least 4 out of 10;

3. Meets American College of Rheumatology 2016 case definition criteria for FM;

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 10mg of Dextromethorphan twice daily or placebo for 4 weeks

4 weeks

Daily self-reported measures

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dextromethorphan
• N/A

Participant Groups

Group I: Dextromethorphan Experimental Treatment 1 Intervention

Participant will take one dextromethorphan 10mg capsule in the morning and at night.

Group II: Placebo Placebo Group 1 Intervention

Participants will take one placebo capsule in the morning and at night.

Dextromethorphan is already approved in United States for the following indications:

Approved in United States as Dextromethorphan for:

• Cough suppression
• Depression (when combined with bupropion as Auvelity)

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

Dextromethorphan/bupropion, a fixed-dose combination medication, was approved in August 2022 for treating major depressive disorder (MDD) in adults, highlighting its efficacy as a new treatment option.

The combination works by utilizing dextromethorphan as an NMDA receptor antagonist and sigma-1 receptor agonist, while bupropion enhances the bioavailability of dextromethorphan, potentially improving therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan/Bupropion: First Approval. Keam, SJ.[2022]

Dextromethorphan (DXM) has been repurposed multiple times, showing its versatility as a treatment for cough, pseudobulbar affect, and now major depressive disorder when combined with bupropion.

The oral formulation of dextromethorphan and bupropion is noted for its rapid action and favorable safety profile, making it a promising option for treating major depressive disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan: From Cough Suppressant to Antidepressant. Kverno, K.[2022]

Auvelity, a combination of dextromethorphan and bupropion, is approved for treating major depressive disorder in adults, but it carries a boxed warning for increased risk of suicidal thoughts and behaviors in younger patients.

Common side effects include dizziness, nausea, and headache, with a risk of seizures at higher doses, highlighting the importance of careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Combination Drug for Depression. Aschenbrenner, DS.[2023]

In a phase 2 trial involving 80 patients with major depressive disorder, dextromethorphan-bupropion (AXS-05) showed a significantly greater reduction in depression symptoms compared to bupropion, with a mean change in MADRS score of -13.7 points versus -8.8 points over 6 weeks.

Dextromethorphan-bupropion also resulted in higher remission rates (46.5% vs. 16.2% at week 6) and response rates (60.5% vs. 40.5% at week 6), while being generally well tolerated with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial. Tabuteau, H., Jones, A., Anderson, A., et al.[2022]

In a phase 3 trial involving 327 patients with major depressive disorder, AXS-05 (dextromethorphan-bupropion) significantly improved depressive symptoms compared to placebo, with effects noticeable as early as week 1.

The treatment led to a remission rate of 39.5% compared to 17.3% for placebo, and was generally well tolerated, with no serious side effects like weight gain or increased sexual dysfunction reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (GEMINI). Iosifescu, DV., Jones, A., O'Gorman, C., et al.[2022]

Dextromethorphan, a widely used nonopioid cough suppressant, has a reassuring safety profile with infrequent and usually mild adverse reactions, primarily dose-related neurological, cardiovascular, and gastrointestinal disturbances.

The most significant safety concern is the potential for abuse, particularly when combined with monoamine oxidase inhibitors (MAOIs), but no major safety risks were found for short-term use, even considering pharmacokinetic variations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan. An overview of safety issues. Bem, JL., Peck, R.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Dextromethorphan/Bupropion: First Approval. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Dextromethorphan: From Cough Suppressant to Antidepressant. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

New Combination Drug for Depression. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (GEMINI). [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Dextromethorphan. An overview of safety issues. [2022]

7. Poland pubmed.ncbi.nlm.nih.gov

Evaluation of the neuroprotective effect of dextromethorphan in the acute phase of ischaemic stroke. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Delirium associated with concomitant use of duloxetine and bupropion in an elderly patient. [2017]