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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a combination of two medications, dextromethorphan (commonly found in cough syrup) and fluoxetine (a common antidepressant), can alleviate symptoms for individuals with obsessive-compulsive disorder (OCD) and related conditions. The trial evaluates the tolerability of this combination and its effectiveness in reducing symptoms. Participants will be divided into two groups: one will begin with both medications, while the other will add dextromethorphan after several weeks of taking fluoxetine alone. Individuals with OCD, body dysmorphic disorder, illness anxiety disorder, or somatic symptom disorder residing in California may be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to early findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is examining the safety and effectiveness of combining dextromethorphan and fluoxetine for treating obsessive-compulsive disorder (OCD). Although specific data on this combination for OCD is limited, both medications have been safely used in other contexts.

Dextromethorphan, commonly found in cough medicines, is usually safe when taken as directed. Fluoxetine, also known as Prozac, is an approved treatment for several mental health conditions, including OCD. It has been used extensively, and studies have shown it to be safe and effective for various disorders.

This trial is in its second phase, indicating that earlier studies did not identify any serious safety issues. This phase focuses on how well participants tolerate the treatment and gathers more information on side effects.

In summary, while specific data on this combination for OCD is not yet available, the individual drugs have been used safely in other settings. The trial aims to confirm that using them together is also safe and effective. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of dextromethorphan and fluoxetine for treating Obsessive-Compulsive Disorder (OCD) because it offers a fresh approach to managing the condition. While most standard OCD treatments, like SSRIs, primarily focus on serotonin levels, dextromethorphan adds a unique twist by potentially affecting glutamate pathways, which may enhance treatment outcomes. This dual-action approach could help patients who don't fully respond to traditional therapies, providing a new hope for faster or more effective relief.

What evidence suggests that this trial's treatments could be effective for OCD?

Research has shown that fluoxetine alone can effectively reduce OCD symptoms. One study with 64 patients found that fluoxetine significantly lessened OCD symptoms compared to a placebo, which contains no active medicine. In this trial, participants in Group A will initially receive fluoxetine alone before adding dextromethorphan. Meanwhile, Group B will start with both fluoxetine and dextromethorphan, then continue with fluoxetine alone. Dextromethorphan, commonly used to suppress coughs, is being studied for its potential mental health benefits. Although specific evidence supporting dextromethorphan for OCD is not yet available, early research is exploring how it might work with fluoxetine. This combination could be helpful because dextromethorphan affects brain chemicals that fluoxetine also targets. Initial findings suggest that using both together might improve symptom relief. ^{1 3 4 6 7}

Who Is on the Research Team?

Peter van Roessel, MD, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04899687

Study of Dextromethorphan in OCD and Related Disorders

The purpose of the study is to assess the tolerability and efficacy of dextromethorphan in combination with fluoxetine for symptom relief in OCD and related ...

2.

withpower.com

withpower.com/trial/phase-3-obsessive-compulsive-disorder-8-2021-1603c

Dextromethorphan + Fluoxetine for Obsessive-Compulsive ...

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 ...

3.

trial.medpath.com

trial.medpath.com/clinical-trial/cad1b1c8e91817d1/irct20090117001556n158-dextromethorphan-fluoxetine-ocd-treatment

Dextromethorphan and Fluoxetine for the treatment of OCD

Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0010440X2200058X

Treatment-resistant OCD: Pharmacotherapies in adults

While no data yet support use of dextromethorphan in OCD, an open-label pilot study testing the combination of dextromethorphan and fluoxetine—also a potent ...

5.

med.stanford.edu

med.stanford.edu/mosslab/research/_jcr_content/main/clinicaltrials.html?ctid=NCT04899687&conditionId=&serviceLineId=&condition=&alpha=s

Study of Dextromethorphan in OCD and Related Disorders

The purpose of the study is to assess the tolerability and efficacy of dextromethorphan in combination with fluoxetine for symptom relief in OCD and related ...

6.

trialfinder.panfoundation.org

trialfinder.panfoundation.org/en-US/trial/listing/541315

Study of Dextromethorphan in OCD and Related Disorders

The purpose of the study is to assess the tolerability and efficacy of dextromethorphan in combination with fluoxetine for symptom relief in ...

7.

stanfordhealthcare.org

stanfordhealthcare.org/trials/s/NCT04899687.html

Study of Dextromethorphan in OCD and Related Disorders

The purpose of the study is to assess the tolerability and efficacy of dextromethorphan in combination with fluoxetine for symptom relief in OCD and related ...