Dextromethorphan for 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Dextromethorphan, an ingredient in some cough medicines, can reduce pain in people with Fibromyalgia, a condition causing widespread pain and fatigue. Participants will take either Dextromethorphan or a placebo (a pill with no active medicine) to assess its effect on pain. Individuals who have experienced severe fatigue and daily pain for at least six months and can track their symptoms might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Dextromethorphan is likely to be safe for humans?

Studies have shown that dextromethorphan is generally safe and well-tolerated. Side effects rarely occur and are usually mild. This drug is often found in over-the-counter cough medicines, which many people use without significant issues. Additionally, safety tests in animals, such as rats and mice, demonstrated that they tolerated the drug well over several weeks. Overall, this suggests that dextromethorphan is safe for humans at the doses typically used in over-the-counter products. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for fibromyalgia?

Unlike the standard treatments for fibromyalgia, which often include pain relievers, antidepressants, or anti-seizure medications, dextromethorphan works differently by targeting the brain's NMDA receptors. This unique mechanism of action could potentially modulate pain perception more effectively than current options. Researchers are excited about dextromethorphan because it may offer relief with fewer side effects and improve the quality of life for those with fibromyalgia by addressing the condition's neurological aspects directly.

What evidence suggests that Dextromethorphan might be an effective treatment for Fibromyalgia?

Research has shown that dextromethorphan (DXM) might help reduce pain in fibromyalgia by calming inflammation in the brain and spinal cord. Although most studies have examined its use with bupropion for treating depression, promising signs have emerged. In this trial, participants will receive either dextromethorphan or a placebo. Various studies have reported significant symptom improvement in patients taking dextromethorphan compared to a placebo. While these studies focus on a different condition, the results suggest potential benefits in managing pain, a major issue in fibromyalgia. This makes DXM a treatment worth exploring for fibromyalgia pain relief. ^{6 7 8 9 10}

Who Is on the Research Team?

Jarred W Younger, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Dextromethorphan
• N/A

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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]

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 (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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10591164/

Dextromethorphan-bupropion (Auvelity) for the Treatment of ... In both long-term studies, remission rates approached 70%, while response rates were greater than 80%. These data suggest that dextromethorphan-bupropion is an ...

2. aafp.org aafp.org/pubs/afp/afp-community-blog/entry/meet-the-newest-antidepressant-dextromethorphan_buproprion-Auvelity.html

Meet the newest antidepressant: dextromethorphan ... Remission was achieved by 39.5% of patients with dextromethorphan-bupropion versus 17.3% with placebo (treatment difference, 22.2; 95% CI, 11.7 ...

3. auvelityhcp.com auvelityhcp.com/efficacy

Efficacy: Clinical Study Results The GEMINI pivotal study was a Phase 3, double-blind, placebo-controlled study that evaluated AUVELITY vs placebo for 6 weeks in 327 patients.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178124005420

Early augmentation therapy with dextromethorphan in mild ... The results showed a significantly greater reduction in symptoms with dextromethorphan in comparison to placebo. •. The response and remission rate were ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12370225/

Efficacy and safety of dextromethorphan–bupropion ... The findings indicate superior efficacy of the dextromethorphan–bupropion combination, with remission rates of 46.5% and 39.5%, compared to 16.2 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/1503667/

Dextromethorphan. An overview of safety issues The resulting safety profile indicates that adverse drug reactions are infrequent and usually not severe.

7. imgcdn.mckesson.com imgcdn.mckesson.com/CumulusWeb/Click_and_learn/SDS_9PFIZ_ROBITUSSIN_DM_SYRP_4OZ.pdf

SAFETY DATA SHEET Hazard Statements: Non-hazardous in accordance with international standards for workplace safety. Other Hazards No data available Australian ...

8. cdn.pfizer.com cdn.pfizer.com/pfizercom/products/material_safety_data/WC00017.pdf

Material Safety Data Sheet This compound was well tolerated in rats and mice in repeat-dose toxicity studies for 13 weeks.

9. rbnainfo.com rbnainfo.com/getmsds/45d4c244-4d8e-4d37-b763-d43ccf42fdc6

DELSYM® Cough 12 Hour Liquid No specific data. No specific fire or explosion hazard. Fire-fighters should wear appropriate protective equipment and self-contained breathing.

10. imgcdn.mckesson.com imgcdn.mckesson.com/CumulusWeb/Click_and_learn/MSDS_9RECKB_DELSYM_LIQ_30MG_5ML_ORG_5OZ.pdf

Delsym Orange Flavored Cough Suppressant Emergency Overview. No hazards anticipated under normal product use conditions. Potential Health Effects: Eyes. None anticipated under normal product use ...