Celecoxib for Major Depressive Disorder

Overseen By Alexandra Checkers, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Stony Brook University

Must not be taking: Digoxin, Antihypertensives, Diuretics, others

Disqualifiers: Low TSPO binders, Celecoxib allergy, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests celecoxib, a medication typically used for pain and inflammation, to determine if it can reduce depression symptoms in people with major depressive disorder (MDD). Researchers will use special brain scans to see if celecoxib lowers inflammation in specific brain areas linked to mood. Suitable participants have MDD, are currently experiencing a major depressive episode, and do not have allergies to certain pain medications. The trial aims to discover if reducing brain inflammation can improve depression symptoms and potentially lead to better treatments for those with MDD. As a Phase 4 trial, celecoxib is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications before joining the trial. Specifically, you cannot take medications that interact with celecoxib or have anti-inflammatory or immune-modulating effects. There is also a required period without these medications before starting celecoxib.

What is the safety track record for celecoxib?

Research has shown that taking 400 mg of celecoxib daily is generally safe for people with mood disorders. In studies where patients took this dose for up to 12 weeks, most did not experience serious side effects. Some individuals with depression reported improvement while taking celecoxib, though results varied across studies. Overall, celecoxib appears promising for treating mood disorders without major safety concerns. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Celecoxib is unique because it targets inflammation, which is not a common focus in treating major depressive disorder (MDD). Most treatments for MDD, like SSRIs and SNRIs, work by altering neurotransmitter levels in the brain. Celecoxib, on the other hand, is a nonsteroidal anti-inflammatory drug (NSAID) that could address depression by reducing inflammation, a novel approach in this field. Researchers are excited because this could provide a new avenue for treating depression, especially for patients who do not respond well to traditional antidepressants.

What evidence suggests that celecoxib might be an effective treatment for major depressive disorder?

Research shows that celecoxib, which participants in this trial will receive, can help treat major depressive disorder (MDD) by reducing brain inflammation. Some studies found that adding celecoxib to regular depression treatments improved recovery rates by 15-30%. In certain patients, celecoxib also lowered depression severity, as measured by the Hamilton Depression Rating Scale, a standard test for assessing depression severity. Reviews combining data from multiple studies have consistently found that celecoxib outperforms a placebo (a pill with no active ingredients). While not all studies agree, these findings suggest that celecoxib might help reduce depression symptoms by targeting brain inflammation. ^{2 3 5 6 7}

Who Is on the Research Team?

Christine DeLorenzo, PhD

Principal Investigator

Stony Brook University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with Major Depressive Disorder (MDD) currently experiencing a major depressive episode. Participants must score at least 29 on the MADRS, which measures depression severity. People who are pregnant, breastfeeding, or planning to conceive during the study; have certain genetic traits affecting drug metabolism; severe allergies to celecoxib or similar drugs; heart, liver, kidney issues; recent GI bleeding or peptic ulcers can't join.

Inclusion Criteria

I am currently experiencing a major depressive episode.

Your depression severity score on the MADRS (Montgomery-Åsberg Depression Rating Scale) is 29 or higher.

I understand the details of the trial and can consent to participate.

Exclusion Criteria

I haven't taken any anti-inflammatory or immune-modifying drugs recently.

You are allergic to celecoxib, sulfonamides, aspirin, or other medications like NSAIDs. You have had asthma, hives, or allergic reactions when taking aspirin or other NSAIDs in the past.

I am on medications that could interact with celecoxib.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 400 mg/day of celecoxib for 8 weeks, with PET scans and HDRS scores obtained at each time point

8 weeks

2 visits (in-person) for PET scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Celecoxib

Trial Overview The trial tests if Celecoxib (400 mg daily), an anti-inflammatory drug, reduces neuroinflammation and eases symptoms in MDD patients. It involves PET scans using [18F]FEPPA tracer before and after an 8-week treatment period to measure changes in brain inflammation and correlate these with symptom improvement as per HDRS scores.

How Is the Trial Designed?

Group I: Celecoxib 400 mg Experimental Treatment 1 Intervention

Patients will receive 400 mg/day of celecoxib for 8 weeks.

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

Approved in United States as Celebrex for:

• Pain relief
• Inflammation
• Osteoarthritis
• Rheumatoid arthritis
• Menstrual cramps
• Colorectal polyps prevention

Approved in European Union as Celebrex for:

• Symptomatic relief in osteoarthritis
• Symptomatic relief in rheumatoid arthritis
• Ankylosing spondylitis
• Acute pain
• Primary dysmenorrhea
• Adenomatous polyposis coli

Approved in Canada as Celebrex for:

• Symptomatic relief of osteoarthritis
• Symptomatic relief of rheumatoid arthritis
• Ankylosing spondylitis
• Acute pain
• Primary dysmenorrhea

Who Is Running the Clinical Trial?

Stony Brook University

Lead Sponsor

Trials

225

Recruited

41,700+

Brain & Behavior Research Foundation

Collaborator

Trials

63

Recruited

2,900+

Published Research Related to This Trial

In a study involving 32 patients with major depressive disorder (MDD) and 20 healthy controls, the COX-2 inhibitor celecoxib significantly reduced depression symptoms when added to reboxetine treatment, as measured by the Hamilton Depression Scale.

The study found elevated levels of macrophage migration inhibitory factor (MIF) and reduced levels of transforming growth factor-β (TGF-β) in depressed patients, suggesting a link between immune response and depressive symptoms, although the sample size was small.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elevated macrophage migration inhibitory factor and decreased transforming growth factor-beta levels in major depression--no influence of celecoxib treatment. Musil, R., Schwarz, MJ., Riedel, M., et al.[2018]

Celecoxib, a selective COX-2 inhibitor, offers the benefit of fewer gastrointestinal side effects compared to traditional nonsteroidal anti-inflammatory drugs (NSAIDs), making it a safer option for managing musculoskeletal symptoms and pain.

While higher doses of celecoxib do increase cardiovascular risk, this risk is similar to that associated with nonselective NSAIDs, highlighting the need for careful consideration of individual patient risks and benefits when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celecoxib in arthritis: relative risk management profile and implications for patients. McKellar, G., Singh, G.[2021]

Celecoxib is an effective treatment for various types of arthritis and pain management, offering improved gastrointestinal tolerability compared to nonselective NSAIDs, making it a safer option for patients at risk of GI issues.

While there is some inconsistency regarding its cardiovascular risk, any potential increase is likely small and comparable to that of nonselective NSAIDs, suggesting celecoxib is a reasonable choice for patients with low cardiovascular risk who need NSAID therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celecoxib: a review of its use in the management of arthritis and acute pain. Frampton, JE., Keating, GM.[2021]

In a study involving 40 patients with major depression, the addition of the COX-2 inhibitor celecoxib to reboxetine treatment resulted in significantly greater improvements in depressive symptoms compared to reboxetine alone over a 6-week period.

The positive effects of celecoxib suggest a link between inflammation and major depression, indicating that targeting inflammatory processes may enhance the effectiveness of traditional antidepressant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Müller, N., Schwarz, MJ., Dehning, S., et al.[2022]

A meta-analysis of 29 randomized controlled studies involving 847 patients with depression found that celecoxib, a selective COX2 inhibitor, has a significant anti-depressant effect, suggesting it could be a viable treatment option.

Despite the overall positive findings, there was considerable heterogeneity in the results, likely due to differences in depression types and scales used, indicating that further research is needed to clarify its efficacy across various depression subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of celecoxib on improving depression: A systematic review and meta-analysis. Wang, Z., Wu, Q., Wang, Q.[2022]

Celecoxib, an NSAID, may improve outcomes in patients with major depressive disorder when used alongside antidepressants, based on four small randomized controlled trials involving a total of 160 participants.

Despite some potential benefits, there are concerns about adverse effects and drug interactions with NSAIDs, making their use in treating depression a cautious and tentative approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressant augmentation with anti-inflammatory agents. Andrade, C.[2022]

In a study of 40 patients with major depressive disorder, celecoxib significantly reduced serum IL-6 levels and depressive symptoms compared to a placebo, suggesting its antidepressant effect may be linked to its anti-inflammatory properties.

Patients taking celecoxib experienced higher rates of response (95%) and remission (35%) compared to those on placebo (50% and 5%), indicating that celecoxib is both effective and safe as an adjunct treatment for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of celecoxib add-on treatment on symptoms and serum IL-6 concentrations in patients with major depressive disorder: randomized double-blind placebo-controlled study. Abbasi, SH., Hosseini, F., Modabbernia, A., et al.[2022]

In the PREDDICT study involving 122 participants, switching to vortioxetine from other antidepressants was found to be safe and well-tolerated, with mild side effects reported during the transition.

Participants experienced a significant reduction in depression symptoms, as indicated by a decrease in the Montgomery-Åsberg Depression Rating Scale scores over the first four weeks of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Switching Strategies of Various Antidepressants to Vortioxetine in the PREDDICT Trial. Mills, NT., Sampson, E., Fourrier, C., et al.[2022]

Celecoxib is a selective COX-2 inhibitor that offers similar pain relief as traditional NSAIDs but has a safer gastrointestinal profile, making it a preferable option for patients at risk of GI complications.

Despite its GI safety, celecoxib carries similar risks of other adverse effects as NSAIDs, and caution is advised for certain populations, including the elderly and those with cardiovascular issues, as it does not provide antithrombotic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety of celecoxib administration]. Babić-Naglić, D.[2017]

A postmarketing analysis of 31,024 adverse event reports linked to rofecoxib revealed a significant incidence of serious adverse events, particularly hemorrhage, thrombosis, and embolism, with a notable risk increase in patients using anticoagulants or NSAIDs.

The data suggests that rofecoxib users face heightened risks for cardiovascular issues and hemorrhagic events, especially among older males and those taking blood thinners, indicating a need for careful monitoring in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing surveillance of serious adverse events associated with the use of rofecoxib from 1999-2002. Bottone, FG., Barry, WT.[2019]

Celecoxib, when added to standard treatment, significantly reduces depressive symptoms in patients with unipolar depression, as shown by a decrease in Hamilton Depression Rating Scale scores at both 4 and 6 weeks.

Patients receiving celecoxib also had much higher rates of treatment response and remission compared to those on placebo, indicating its potential effectiveness as an add-on therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celecoxib: a new augmentation strategy for depressive mood episodes. A systematic review and meta-analysis of randomized placebo-controlled trials. Faridhosseini, F., Sadeghi, R., Farid, L., et al.[2018]

Celecoxib is effective for treating osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, showing significant efficacy compared to placebo and similar effectiveness to other pain relievers like paracetamol and nonselective NSAIDs.

Celecoxib has a lower incidence of upper gastrointestinal complications compared to nonselective NSAIDs, making it a safer option for patients at risk of GI toxicity, although caution is advised when used with low-dose aspirin due to potential cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celecoxib: a review of its use for symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. McCormack, PL.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9372844/

Effect of celecoxib on improving depression: A systematic ... The data on the efficacy of celecoxib on improving depression are inconsistent. Some studies showed celecoxib could improve depression[8,9]. On the contrary, a ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666354624001492

Efficacy of inflammation-based stratification for add-on ... Based on previous studies, we expect immune-targeted augmentation with minocycline or celecoxib to yield a superior remission rate of 15-30% compared to ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04814355

The Effect of Celecoxib on Neuroinflammation in MDD Clinical studies have observed that, in a subset of depressed patients, celecoxib treatment reduced depression severity as assessed by the Hamilton Depression ...

4. mdpi.com mdpi.com/2077-0383/12/10/3497

Celecoxib for Mood Disorders: A Systematic Review and ... Celecoxib at a dose of 400 mg/d used for up to 12 weeks appeared to be a safe treatment in patients with mood disorders.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9830720/

Anti-Inflammatory Treatment Efficacy in Major Depressive ... All meta-analyses demonstrated superiority of celecoxib over placebo. SMD ranged between −0.82 and 3.43 for mean difference, signs depending on ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10218898/

Celecoxib for Mood Disorders: A Systematic Review and Meta ... Celecoxib at a dose of 400 mg/d used for up to 12 weeks appeared to be a safe treatment in patients with mood disorders.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178116309891

Efficacy and safety of celecoxib monotherapy for mild to ... The current pilot study provided concrete evidence of significantly superior and faster antidepressant effects by celecoxib monotherapy (200 mg, two capsules ...