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?

The goal of this trial is to pilot a way for orthopaedic surgeons to safely screen for depression and provide treatment for depression with medication. The main questions it aims to answer are: 1. What are the outcomes of patients who screen positive for depressive symptoms and are prescribed either an Selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI). 2. What are the outcomes of patients who screen positive for depressive symptoms and choose not to pursue treatment with medication?

Will I have to stop taking my current medications?

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

Is duloxetine generally safe for humans?

Duloxetine has been studied for various conditions, including depression and knee osteoarthritis, and is generally considered safe for humans. Some people may experience side effects like nausea, weight gain, or palpitations, but these are usually mild or moderate. ^{1 2 3 4 5}

What makes the drug unique for depression in orthopedic trauma patients?

Duloxetine is unique because it is a dual reuptake inhibitor of serotonin and norepinephrine, which can provide more effective and faster antidepressant effects compared to other common medications. It is also used for a wide variety of conditions, including chronic musculoskeletal pain, which may be relevant for orthopedic trauma patients. ^{3 6 7 8 9}

What data supports the effectiveness of the drug duloxetine for depression in orthopedic trauma patients?

Duloxetine is effective in treating depression and has shown benefits in managing pain and improving quality of life in patients with knee osteoarthritis, which often co-occurs with depression. This suggests it may help orthopedic trauma patients who experience both pain and depression. ^{1 3 9 10 11}

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]

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 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 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]

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]

Citations

1. United States 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. [2023]

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

An Updated Systematic Review and Meta-analysis of Duloxetine for Knee Osteoarthritis Pain. [2023]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy and safety of duloxetine in osteoarthritis: a systematic review and meta-analysis. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Duloxetine: a review. [2009]

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

The efficacy and safety of duloxetine for the treatment of patients after TKA or THA: A systematic review and meta-analysis. [2023]

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

Long-term tolerability and effectiveness of duloxetine in the treatment of major depressive disorder. [2015]

7. United States 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. [2022]

8. Australia 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. [2022]

9. United States 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. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Duloxetine versus other anti-depressive agents for depression. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Current Opinions about the Use of Duloxetine: Results from a Survey Aimed at Psychiatrists. [2023]