Dextromethorphan + Fluoxetine for Obsessive-Compulsive Disorder

Overseen By Pavithra Mukunda, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must be taking: Fluoxetine

Must not be taking: Psychotropic medications

Disqualifiers: Bipolar, Psychotic, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if a common cough medicine can help when taken with a low dose of a usual obsessive-compulsive disorder (OCD) medication. It targets patients with OCD and related disorders who often do not get enough help from current treatments. The cough medicine might work with the usual drug to better control troubling thoughts and actions. The usual medication is a well-established treatment for obsessive-compulsive disorder and has been shown to be effective in multiple studies.

Will I have to stop taking my current medications?

If you are taking any prescribed psychotropic medications other than fluoxetine, you will need to stop them at least 2 weeks before the study starts.

What evidence supports the effectiveness of the drug combination of Dextromethorphan and Fluoxetine for treating Obsessive-Compulsive Disorder?

Research shows that combining fluoxetine with another drug, clomipramine, can be effective for treating obsessive-compulsive disorder, especially when each drug alone is not enough. This suggests that combining fluoxetine with other drugs, like dextromethorphan, might also be beneficial. ^{1 2 3 4 5}

Is the combination of dextromethorphan and fluoxetine safe for humans?

There is no specific safety data available for the combination of dextromethorphan and fluoxetine, but fluoxetine (also known as Prozac) is generally considered safe for treating conditions like depression and obsessive-compulsive disorder. However, it's important to be cautious about potential drug interactions, as combining medications can sometimes lead to unexpected side effects. ^{2 4 6 7 8}

How is the drug combination of Dextromethorphan and Fluoxetine unique for treating obsessive-compulsive disorder?

The combination of Dextromethorphan and Fluoxetine for treating obsessive-compulsive disorder is unique because it combines a cough suppressant (Dextromethorphan) with an antidepressant (Fluoxetine), potentially offering a novel mechanism of action compared to traditional treatments that primarily focus on serotonin reuptake inhibition. ^{2 3 4 9 10}

Research Team

Peter van Roessel, MD, PhD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for California residents with OCD, body dysmorphic disorder, illness anxiety disorder, or somatic symptom disorder who can consent to participate. It excludes those with bipolar or psychotic disorders, pregnant or nursing women, recent users of certain psychotropic drugs other than fluoxetine, and individuals with current severe substance use issues.

Inclusion Criteria

I have been diagnosed with OCD, BDD, IAD, or SSD.

I understand and can agree to the study's procedures and risks.

Living within California

Exclusion Criteria

Pregnant or nursing women

I have bipolar or psychotic disorder.

Active moderate or severe substance use disorder, lifetime severe substance use disorder

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants in Group A take fluoxetine for 4 weeks; Group B takes fluoxetine plus dextromethorphan with increasing doses weekly for 4 weeks

4 weeks

Treatment Phase 2

Participants in Group A continue fluoxetine and add dextromethorphan with increasing doses weekly for 4 weeks; Group B continues fluoxetine alone for 4 weeks

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dextromethorphan
• Fluoxetine

Trial Overview The study tests the combination of dextromethorphan and fluoxetine for treating symptoms in patients with OCD and related conditions. The goal is to determine how well patients tolerate this combo and its effectiveness in symptom relief.

Participant Groups

Group I: Group B: fluoxetine plus dextromethorphan then fluoxetine Experimental Treatment 2 Interventions

Group B participants will take fluoxetine 20mg (or prior dose) daily together with over the counter dextromethorphan, with doses increasing weekly as tolerated, for 4 weeks, and then will stop dextromethorphan, continuing fluoxetine alone for 4 weeks.

Group II: Group A: fluoxetine then fluoxetine plus dextromethorphan Experimental Treatment 2 Interventions

Group A participants will take fluoxetine 20mg (or prior dose) daily for 4 weeks, and will then continue fluoxetine while adding over the counter dextromethorphan, with doses increasing weekly as tolerated, for 4 weeks.

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?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Avy L. & Roberta L. Miller Foundation

Collaborator

Trials

1

Recruited

60+

Findings from Research

The combination therapy of fluvoxamine and clomipramine in six adolescents with treatment-resistant OCD was well tolerated, allowing for lower doses of clomipramine than typically required when used alone.

Fluvoxamine effectively inhibited the metabolism of clomipramine, suggesting a potential for optimizing treatment and minimizing side effects, although further studies are needed to confirm the efficacy of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Review of Fluvoxamine-Clomipramine Combination Therapy in Obsessive-Compulsive Disorder in Children and Adolescents. Fung, R., Elbe, D., Stewart, SE.[2022]

Clomipramine may be beneficial in augmenting SSRI treatment for OCD patients who do not respond to SSRIs alone, but this combination carries significant risks of drug interactions that can increase adverse effects.

The combination can lead to dangerously high blood levels of either medication, particularly clomipramine, which can cause severe side effects like seizures, highlighting the need for careful dosing and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmenting selective serotonin reuptake inhibitors with clomipramine in obsessive-compulsive disorder: benefits and risks. Andrade, C.[2022]

A combination of clomipramine and fluoxetine was tested in 6 adolescents with OCD, showing marked improvements in 5 patients and moderate improvements in 1, suggesting enhanced efficacy compared to clomipramine alone.

The combination therapy was well tolerated, with fewer adverse effects compared to clomipramine used alone, indicating that lower doses of both medications can effectively treat OCD while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of adolescent obsessive-compulsive disorder with a clomipramine-fluoxetine combination. Simeon, JG., Thatte, S., Wiggins, D.[2014]

The combination of clomipramine and fluoxetine was beneficial in treating severe obsessive-compulsive disorder (OCD) in four cases, demonstrating effectiveness when either drug alone was insufficient.

In two instances, adding fluoxetine to clomipramine not only enhanced treatment outcomes but also did so without introducing additional side effects, suggesting a safe and effective adjunctive therapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The benefits of clomipramine-fluoxetine combination in obsessive compulsive disorder. Browne, M., Horn, E., Jones, TT.[2019]

In a 10-week double-blind, placebo-controlled trial involving 27 outpatients with obsessive-compulsive disorder, clomipramine was found to be significantly more effective than a placebo.

This study supports the efficacy of clomipramine as a treatment option for individuals diagnosed with obsessive-compulsive disorder according to DSM-III-R criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obsessive-compulsive disorder: a double-blind, placebo-controlled trial of clomipramine in 27 patients. Jenike, MA., Baer, L., Summergrad, P., et al.[2013]

Atomoxetine significantly inhibits the metabolism of dextromethorphan, suggesting a potential drug-drug interaction that could affect patients with ADHD, as both drugs are metabolized by the CYP 2D6 enzyme.

In contrast, dl-methylphenidate does not appear to interact with dextromethorphan, indicating that it is unlikely to influence the metabolism of this cough suppressant in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential interactions of methylphenidate and atomoxetine with dextromethorphan. Ciccone, PE., Ramabadran, K., Jessen, LM.[2019]

Fluvoxamine has a favorable safety profile based on 17 years of post-marketing surveillance involving approximately 28 million patients, showing low incidences of serious adverse effects like suicidality and sexual dysfunction.

The drug is well-tolerated, with mild withdrawal symptoms reported but no evidence of drug dependence, confirming its safety as a treatment for depression and obsessive-compulsive disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluvoxamine: safety profile in extensive post-marketing surveillance. Buchberger, R., Wagner, W.[2022]

A case of serotonin syndrome was documented in a 26-year-old woman after combining fluvoxamine and mirtazapine, highlighting the risks of drug interactions in patients with complex medical histories.

Clinicians should be vigilant about the potential for serotonin syndrome when prescribing multiple medications that affect serotonin levels, especially in patients with conditions like anorexia nervosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serotonin syndrome induced by fluvoxamine and mirtazapine. Demers, JC., Malone, M.[2022]

In a study of 20 outpatients with treatment-resistant obsessive-compulsive disorder (OCD), the combination of citalopram and clomipramine led to significant improvement in about 50% of patients after one month and continued effectiveness over a year.

The study suggests that combining these two serotonergic medications is a potentially useful and well-tolerated strategy for patients who have not responded to standard treatments, although further controlled studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of long-term augmentation with citalopram to clomipramine in treatment-resistant OCD patients. Marazziti, D., Golia, F., Consoli, G., et al.[2022]

In a 10-week trial with 64 patients, fluoxetine (80 mg/day) was found to be significantly more effective than placebo in reducing OCD symptoms, while phenelzine (60 mg/day) showed limited effectiveness overall.

Phenelzine may only benefit a specific subgroup of OCD patients with symmetry obsessions, as the study did not find evidence supporting its use for the broader OCD population or those with high anxiety levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of fluoxetine and phenelzine for obsessive-compulsive disorder. Jenike, MA., Baer, L., Minichiello, WE., et al.[2022]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Retrospective Review of Fluvoxamine-Clomipramine Combination Therapy in Obsessive-Compulsive Disorder in Children and Adolescents. [2022]

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

Augmenting selective serotonin reuptake inhibitors with clomipramine in obsessive-compulsive disorder: benefits and risks. [2022]

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

Treatment of adolescent obsessive-compulsive disorder with a clomipramine-fluoxetine combination. [2014]

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

The benefits of clomipramine-fluoxetine combination in obsessive compulsive disorder. [2019]

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

Obsessive-compulsive disorder: a double-blind, placebo-controlled trial of clomipramine in 27 patients. [2013]

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

Potential interactions of methylphenidate and atomoxetine with dextromethorphan. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Fluvoxamine: safety profile in extensive post-marketing surveillance. [2022]

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

Serotonin syndrome induced by fluvoxamine and mirtazapine. [2022]

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

Effectiveness of long-term augmentation with citalopram to clomipramine in treatment-resistant OCD patients. [2022]

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

Placebo-controlled trial of fluoxetine and phenelzine for obsessive-compulsive disorder. [2022]