Fluoxetine for Obsessive-Compulsive Disorder

Overseen By Stephen Kichuk, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Yale University

Must be taking: Fluoxetine

Must not be taking: Coumadin, MAOIs

Disqualifiers: Substance use disorder, Psychotic disorder, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 18 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how fluoxetine (Prozac), a common medication, affects people with obsessive-compulsive disorder (OCD). Researchers use special brain imaging to observe the brain's response to this treatment. Individuals with significant OCD symptoms who aren't currently on medication and are seeking treatment might be suitable candidates. The study also includes a comparison group of healthy individuals without OCD to aid in interpreting the results. As a Phase 1 and Phase 2 trial, this research focuses on understanding the treatment's effects and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to early-stage treatment insights.

Will I have to stop taking my current medications?

Yes, participants must not be on any current psychoactive medication, except for occasional use of sleep aids. There is also a requirement to not have used psychotropic medications in the past 8 weeks.

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

Research has shown that fluoxetine is generally safe for people with obsessive-compulsive disorder (OCD). The FDA has approved this medication for treating OCD, confirming its safety for this purpose.

Studies have found that most people tolerate fluoxetine well. Common side effects include nausea, headaches, or trouble sleeping, but these are usually mild. Even at higher doses, it remains safe for OCD patients, with similar side effects across different dose levels.

Overall, fluoxetine is a well-established treatment for OCD with a strong safety record. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fluoxetine is unique because it's one of the few medications that specifically targets serotonin reuptake in the brain, which is crucial in managing obsessive-compulsive disorder (OCD) symptoms. Unlike other treatments for OCD that might take longer to show effectiveness, such as cognitive-behavioral therapies or other antidepressants like clomipramine, fluoxetine has the potential to provide earlier symptom relief. Researchers are excited because it could offer a more immediate option for individuals struggling with OCD, potentially improving their quality of life more quickly than current alternatives.

What is the effectiveness track record for fluoxetine in treating obsessive-compulsive disorder?

Research has shown that fluoxetine effectively treats obsessive-compulsive disorder (OCD). Studies have found that taking 40 to 60 mg per day can significantly reduce OCD symptoms. Both open-label studies, where participants know their treatment, and placebo-controlled trials, where the treatment is compared to a placebo, support these findings. Psychiatrists' real-world experiences also highlight fluoxetine's positive effects on OCD. In this trial, participants in the OCD group will receive fluoxetine, either immediately or after a 6-week placebo lead-in, to further evaluate its effectiveness. Overall, fluoxetine is a well-known treatment that helps many patients manage their OCD symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Christopher Pittenger, MD, PhD

Principal Investigator

Professor of Psychiatry; Director, Yale OCD Research Clinic

Are You a Good Fit for This Trial?

This trial is for adults with Obsessive-Compulsive Disorder (OCD) who are seeking treatment and appropriate for fluoxetine therapy. They must not be on psychoactive medication, pregnant, or have a family history of certain disorders. Healthy controls matched by demographics are also included.

Inclusion Criteria

Ability and willingness to participate in all study procedures, including clinical assessments and fMRI scans.

My family does not have a history of OCD or related disorders.

Signed informed consent, approved by the Yale Human Investigations Committee.

Exclusion Criteria

I have used sleep aids or painkillers within 3 days before a scan.

Pregnancy.

Any unstable medical, psychiatric, or neurological condition (including active or otherwise problematic suicidality) that may necessitate urgent treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo baseline fMRI imaging to establish initial brain network data

1 week

1 visit (in-person)

Treatment

OCD participants receive either immediate or placebo-delayed SSRI treatment, with fMRI imaging conducted over the course of treatment

18 weeks

Multiple visits (in-person) for imaging and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fluoxetine

Trial Overview The study tests the effects of immediate versus delayed treatment with Fluoxetine on brain function in OCD patients using advanced fMRI scans to find predictors and changes associated with the drug's response.

How Is the Trial Designed?

Group I: OCD Group Experimental Treatment 2 Interventions

The OCD group will comprise of unmedicated individuals with clinically significant OCD symptoms. OCD Subjects will be randomized, double-blind, to receive immediate or delayed (by 6 weeks as a placebo lead-in) pharmacotherapy.

Group II: Healthy Controls Active Control 1 Intervention

The healthy control group will be an age matched sample of unmedicated healthy adults who will be recruited and imaged once at baseline and the data compared with that of OCD subjects at baseline.

Fluoxetine is already approved in United States, European Union for the following indications:

Approved in United States as Prozac for:

• Depression
• Anxiety
• Obsessive-compulsive disorder
• Bulimia nervosa
• Panic disorder

Approved in European Union as Prozac for:

• Major depressive episodes
• Obsessive-compulsive disorder
• Bulimia nervosa

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In an 8-week study involving 53 patients with obsessive-compulsive disorder (OCD), fluoxetine (FLX) at doses of 40 mg or higher significantly improved symptoms compared to placebo and the lower 20 mg dose.

The treatment was particularly effective in reducing compulsions more than obsessions, although a notable placebo effect was also observed, especially in the compulsion scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of fluoxetine in Austrian patients with obsessive-compulsive disorder. Zitterl, W., Meszaros, K., Hornik, K., et al.[2022]

The review evaluates the effectiveness of orthodontics in correcting dental malocclusions and improving cosmetic appearance in adults, highlighting advancements in materials and techniques.

It categorizes diagnostic variables and therapeutic options, addressing various discrepancies such as alignment and soft-tissue issues, which are crucial for tailored treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esthetic considerations in adult orthodontic treatment. Salama, M., Sarne, O.[2005]

Early treatment of Class III malocclusion using rapid palatal expansion and maxillary protraction can significantly improve facial appearance and psychosocial development in children, as demonstrated in a case report.

With proper compliance, most patients achieved overcorrection in less than a year, and long-term follow-up over 5 years showed no tendency for relapse, indicating the effectiveness and stability of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of skeletal class III malocclusion treated by manifold approach: 5 year follow-up. Tubaki, R., Sharmada, BK., Pai, SS., et al.[2016]

In a pilot study of 10 outpatients with OCD, a rapid increase in fluoxetine dosage led to depressive symptoms in 6 patients, highlighting the need for careful monitoring when adjusting doses.

Combining fluoxetine with a tricyclic antidepressant improved depressive symptoms in 8 patients, and switching to clomipramine resulted in improvements in both OCD and depression for 5 patients, suggesting alternative treatment strategies for managing co-occurring symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obsessive compulsive disorder, depression, and fluoxetine. Hollander, E., Mullen, L., DeCaria, CM., et al.[2013]

In a 32-week study involving 10 outpatients with obsessive-compulsive disorder, fluoxetine demonstrated significant improvement in obsessive-compulsive symptoms and anxiety within four weeks, with the most substantial benefits observed by eight weeks.

Fluoxetine was well-tolerated by all participants, with no serious side effects reported, indicating it is a safe and effective treatment option for managing obsessive-compulsive disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of long-term fluoxetine treatment of obsessive-compulsive disorder. Frenkel, A., Rosenthal, J., Nezu, A., et al.[2013]

Maxillary protraction significantly promotes growth in the maxilla for patients with skeletal Class III malocclusions, as evidenced by changes in cephalometric measurements after treatment.

Coben analysis effectively identifies the underlying mechanisms of malocclusions and aids in designing treatment plans, showing clear improvements in facial structure and angles related to maxillary development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Using Coben analysis to evaluate the therapeutic effect of maxillary protraction on maxillary maldevelopment]. Jinliang, Z., Xun, L., Yujun, J., et al.[2020]

In a 12-week open clinical trial involving 49 patients with obsessive-compulsive disorder, fluoxetine showed a response rate of 62% among those who completed at least 8 weeks of treatment, indicating its potential effectiveness for many patients.

Despite these promising results, further controlled trials are necessary to confirm fluoxetine's efficacy compared to placebo and other treatments, as well as to determine the best dosage, treatment duration, and relapse rates after stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine treatment of obsessive-compulsive disorder: an open clinical trial. Liebowitz, MR., Hollander, E., Schneier, F., et al.[2013]

In a study of 355 outpatients with obsessive-compulsive disorder (OCD), fluoxetine at doses of 20 mg, 40 mg, and 60 mg per day significantly reduced OCD symptoms compared to placebo, with the highest dose showing the greatest efficacy.

The treatment was generally safe, with only a few adverse events leading to discontinuation, indicating that fluoxetine is a viable option for managing OCD with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter investigation of fixed-dose fluoxetine in the treatment of obsessive-compulsive disorder. Tollefson, GD., Rampey, AH., Potvin, JH., et al.[2019]

Fluoxetine (Prozac) has been associated with suicidal thoughts and behaviors in some patients, particularly due to its potential to cause akathisia, a condition characterized by restlessness and an inability to stay still.

While fluoxetine is generally safer than older antidepressants like tricyclics, it is important to monitor a small subset of patients who may experience these adverse effects, as they could lead to increased suicidal ideation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revisiting fluoxetine (Proxac) and suicidal preoccupations. Tueth, MJ.[2019]

A case report describes a patient with post-stroke depression who experienced unusual episodes of sexual excitement while being treated with fluoxetine, suggesting a potential side effect of this medication.

The episodes were dose-dependent, indicating that higher doses of fluoxetine may increase the likelihood of this side effect, particularly in patients with underlying brain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine and orgasmic sexual experiences. Morris, PL.[2017]

Orthodontic treatment can effectively enhance both tooth alignment and facial aesthetics, as demonstrated in a case study of a patient with maxillary retrusion and a concave profile.

The combination of maxillary expansion and face mask therapy led to significant improvements in the patient's soft tissue profile, particularly in projecting the upper lip.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The importance of the facial profile in orthodontic diagnosis and treatment planning: a patient report. Siqueira, DF., Sousa, MV., Carvalho, PE., et al.[2010]

A study involving 229 patients in Dammam, Saudi Arabia, found that the doctor-patient relationship was the most significant factor influencing patient satisfaction with orthodontic treatment, scoring an average of 4.33 out of 5.

Patients treated in public hospitals reported higher overall satisfaction compared to those in private hospitals, particularly in areas like situational aspects and residual categories, while private hospital patients were more satisfied with dental functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Satisfaction with Orthodontic Treatment Received in Public and Private Hospitals in Dammam, Saudi Arabia. Aljughaiman, A., Alshammari, A., Althumairi, A., et al.[2020]

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]

In a 12-week open trial involving 61 patients with obsessive-compulsive disorder (OCD), fluoxetine significantly improved both depressive and OCD symptoms, suggesting its efficacy as a treatment.

The study found that baseline depression scores did not predict improvement in OCD symptoms, supporting the idea that serotonergic abnormalities play a key role in OCD, independent of depressive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open trial of fluoxetine in obsessive-compulsive disorder. Jenike, MA., Buttolph, L., Baer, L., et al.[2013]

Citations

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Optimal Dose of Serotonin Reuptake Inhibitors for ... The systematic review found that the optimal dose for efficacy was about 40mg fluoxetine equivalent. Tolerability decreased with increased doses.

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International OCD Foundation | Medication An adequate trial of an SSRI for OCD requires eight to 12 weeks, with at least 6 of those weeks at the moderate to high doses required for effective treatment ...

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Fluoxetine (oral route) - Side effects & dosage Fluoxetine is used to treat depression, obsessive-compulsive disorder (OCD), bulimia nervosa, premenstrual dysphoric disorder (PMDD), and panic disorder.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/018936s108lbl.pdf

Label for PROZAC (fluoxetine) - accessdata.fda.gov It should be noted that PROZAC is approved in the pediatric population for Major Depressive Disorder and. Obsessive Compulsive Disorder; and PROZAC in ...

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Pharmacotherapy of obsessive compulsive disorder Combined efficacy and safety data suggest that fluoxetine, 20 mg/day, will be effective in many patients. The therapeutic response emerges slowly and increases ...

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Fluoxetine - StatPearls - NCBI Bookshelf Fluoxetine is an FDA-approved medication that has demonstrated efficacy in treating a spectrum of psychological conditions.

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Off-label higher doses of serotonin reuptake inhibitors in ... OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups.