Antidepressants for Depression in Orthopaedic Trauma Patients

Overseen By Erica Grochowski, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Wake Forest University Health Sciences

Must not be taking: Antidepressants

Disqualifiers: Bipolar, Psychotic disorder, Suicidal ideation, 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: 4

Duration: 12 months

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how treating depression with medication can aid recovery from serious bone injuries, such as arm or leg fractures. It will compare the outcomes of patients taking either fluoxetine or duloxetine, both antidepressants, with those who opt not to use medication. Suitable candidates for this trial include individuals visiting an orthopedic trauma clinic for the first time after bone fracture surgery and experiencing depression symptoms that affect their daily life. As a Phase 4 trial, this research focuses on how FDA-approved treatments can provide additional benefits to patients.

Will I have to stop taking my current medications?

If you are currently taking medication to treat depression, you cannot participate in this trial.

What is the safety track record for these treatments?

Research has shown that both duloxetine and fluoxetine, used in this trial, present some safety concerns. Duloxetine, an SNRI, can weaken bones and increase the risk of fractures, especially in older adults. Fluoxetine, an SSRI, may also impact bones, potentially slowing bone healing and increasing the risk of bone loss, particularly in older individuals.

Although these medications are generally well-tolerated, awareness of these risks is important. Both duloxetine and fluoxetine have FDA approval for treating depression, indicating they have passed numerous safety evaluations. However, prospective trial participants should consult a doctor about these potential side effects and their personal implications. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they explore antidepressant options specifically for patients with orthopedic trauma experiencing depression. Duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), offers a dual mechanism by targeting both serotonin and norepinephrine pathways, which may enhance mood improvement more effectively for trauma-related depression. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is well-known for its efficacy in treating depression and is being studied here for its specific impact on orthopedic trauma patients. Unlike standard care, which often focuses on general antidepressants or therapy, these treatments are tailored to address the unique psychological challenges faced by individuals recovering from physical injuries.

What evidence suggests that this trial's treatments could be effective for depression in orthopaedic trauma patients?

Research has shown that duloxetine, one of the medications studied in this trial, can greatly reduce both pain and symptoms of depression. Studies have found it helps people with long-term pain and is generally safe to use.

Fluoxetine, another medication under investigation, often treats depression and anxiety. Some studies suggest it may also help reduce these symptoms in people who have experienced trauma.

This trial tests both medications for their effectiveness in managing depression, making them possible options for treating depression in patients with orthopedic injuries. ^{6 7 8 9 10}

Who Is on the Research Team?

Meghan K Wally, PhD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults over 18 who speak English or Spanish, have had an orthopaedic trauma surgery, and show signs of depression but aren't currently on antidepressants or have bipolar/psychotic disorders. They must score at least a 5 on the PHQ-9 questionnaire.

Inclusion Criteria

I am seeing an orthopedic trauma specialist for the first time for a broken limb or pelvis.

A score of greater than or equal to 5 on the Patient Health Questionnaire-9 (PHQ-9) at first post-operative visit

Exclusion Criteria

I am currently on medication for depression.

Endorse suicidal ideation

Contraindication/allergy to one of the study medications

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either an SSRI or SNRI medication or are referred to behavioral health resources

12 months

Monthly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at months 3, 6, and 12

What Are the Treatments Tested in This Trial?

Interventions

• Duloxetine
• Fluoxetine
• Observation

Trial Overview The study tests if prescribing Fluoxetine (an SSRI) or Duloxetine (an SNRI), compared to no medication, helps with depression in patients after orthopaedic trauma surgery. It looks at patient outcomes based on these treatments.

How Is the Trial Designed?

Group I: serotonin and norepinephrine reuptake inhibitors (SNRI) Experimental Treatment 1 Intervention

Duloxetine, 30mg once daily

Group II: Selective serotonin reuptake inhibitors (SSRI) Experimental Treatment 1 Intervention

Fluoxetine, 20mg once daily

Group III: Observational Experimental Treatment 1 Intervention

Referral to behavioral health per standard practice and provision of resources for strategices to address depressive symptoms.

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

Approved in United States as Cymbalta for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Fibromyalgia
• Neuropathic Pain
• Chronic Musculoskeletal Pain

Approved in European Union as Cymbalta / Yentreve for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Diabetic Peripheral Neuropathic Pain
• Fibromyalgia
• Stress Urinary Incontinence

Approved in Canada as Cymbalta for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Fibromyalgia
• Neuropathic Pain
• Chronic Musculoskeletal Pain

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

Adding duloxetine to the usual care for knee osteoarthritis (OA) patients with moderate pain is cost-effective, providing significant health benefits (31 additional quality-adjusted life years per 1,000 subjects) at a reasonable cost of $39,300 per quality-adjusted life year.

Implementing a depression screening strategy before prescribing duloxetine also proves beneficial, yielding 17 additional quality-adjusted life years per 1,000 subjects at a cost of $17,000 per quality-adjusted life year, making it a viable option for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Screening for Depressive Symptoms Help Optimize Duloxetine Use in Knee Osteoarthritis Patients With Moderate Pain? A Cost-Effectiveness Analysis. Lenhard, NK., Sullivan, JK., Ross, EL., et al.[2023]

In a long-term study of duloxetine for major depressive disorder involving 177 patients, the treatment maintained efficacy with a mean Hamilton Depression Rating scale score below 7, indicating sustained improvement in depression symptoms over an average of 305 days.

Only 7% of patients experienced clinically significant worsening of depression leading to discontinuation, and while 11.9% discontinued due to adverse events, most were not unique to the long-term phase, suggesting duloxetine is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term tolerability and effectiveness of duloxetine in the treatment of major depressive disorder. Dunner, DL., Wilson, M., Fava, M., et al.[2015]

In a 6-week clinical trial involving 148 children and adolescents with major depressive disorder, duloxetine did not demonstrate significant efficacy compared to placebo, with similar changes in depression scores between the two groups.

The safety profile of duloxetine was consistent with previous findings, showing a higher incidence of treatment-emergent adverse events (TEAEs) in the duloxetine group (78.7%) compared to placebo (62.2%), although most were mild or moderate in severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Duloxetine in Children and Adolescents with Major Depressive Disorder in Japan: A Randomized Double-Blind Placebo-Controlled Clinical Trial Followed by an Open-Label Long-Term Extension Trial. Saito, T., Ishida, M., Nishiyori, A., et al.[2022]

Duloxetine significantly reduces knee osteoarthritis pain and improves physical function, as shown in a systematic review of 6 studies with 2059 patients, indicating its efficacy as a treatment option.

Despite its effectiveness, duloxetine did not show a significant difference in serious adverse events compared to placebo, suggesting it may have a similar safety profile, but further well-controlled studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Updated Systematic Review and Meta-analysis of Duloxetine for Knee Osteoarthritis Pain. Chen, B., Duan, J., Wen, S., et al.[2023]

In a study involving 106 patients undergoing total knee arthroplasty, duloxetine did not significantly reduce pain during ambulation compared to placebo on postoperative day 14, indicating it may not be effective for this specific type of postoperative pain.

While duloxetine did not improve pain outcomes, it was associated with a significant reduction in opioid consumption during the postoperative period, suggesting it may still play a role in multimodal pain management despite not directly alleviating ambulation pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine and Subacute Pain after Knee Arthroplasty when Added to a Multimodal Analgesic Regimen: A Randomized, Placebo-controlled, Triple-blinded Trial. YaDeau, JT., Brummett, CM., Mayman, DJ., et al.[2018]

Duloxetine, an SNRI, has been reported by 163 psychiatrists to be effective and well-tolerated for treating major depressive disorder (MDD), anxiety, and fibromyalgia, showing faster antidepressant effects compared to SSRIs.

Psychiatrists agree on duloxetine's versatility, as it can also alleviate somatic symptoms and neuropathic pain, making it suitable for a variety of patient conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Opinions about the Use of Duloxetine: Results from a Survey Aimed at Psychiatrists. Alvarez-Mon, MA., García-Montero, C., Fraile-Martinez, O., et al.[2023]

Duloxetine was found to be non-inferior to paroxetine in treating major depressive disorder (MDD) over an 8-week period, demonstrating similar efficacy based on the Hamilton Rating Scale for Depression (HAMD(17)).

While both medications had comparable safety profiles, duloxetine showed a significant advantage in reducing back pain compared to paroxetine, although it was associated with higher rates of nausea and palpitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily duloxetine 60 mg in the treatment of major depressive disorder: multicenter, double-blind, randomized, paroxetine-controlled, non-inferiority trial in China, Korea, Taiwan and Brazil. Lee, P., Shu, L., Xu, X., et al.[2022]

Citations

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