Duloxetine for Depression after Broken Bones

(SNRI Trial)

Overseen By Erica Grochowski, MPH

Age: 65+

Sex: Any

Trial Phase: Phase 4

Sponsor: Wake Forest University Health Sciences

Must be taking: SNRIs

Must not be taking: SSRIs, SNRIs, Mood stabilizers

Disqualifiers: Polytrauma, Dementia, Hospice, 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: 4

Duration: 12 months

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the anti-depressant Duloxetine can be safely prescribed to older adults after they leave the hospital following a lower body bone fracture. The researchers aim to understand the challenges of starting this medication immediately after discharge and the prevalence of depression among these patients. The trial seeks participants aged 65 or older who have undergone surgery to repair a broken hip, leg, or similar bone. Participants will take Duloxetine daily and regularly report their progress over the course of a year. As a Phase 4 trial, Duloxetine is already FDA-approved and proven effective, and this research helps determine how it benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking SSRIs, SNRIs, or mood stabilizers.

What is the safety track record for Duloxetine?

Studies have shown that duloxetine is generally safe for humans, as the FDA has approved it to treat depression and anxiety. Research indicates that some patients may experience side effects, such as nausea, dry mouth, and fatigue. Importantly, duloxetine may also increase the risk of falls and bone fractures, especially in older adults, which is a consideration for those with existing bone health concerns. Overall, many tolerate duloxetine well, but discussing potential risks with a healthcare provider before starting treatment is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for depression after an injury, like broken bones, typically involve traditional antidepressants such as SSRIs or SNRIs, which can take several weeks to show full effectiveness. Duloxetine is unique because it is a dual-action SNRI that not only helps alleviate depressive symptoms but also targets pain, which is a common issue after bone fractures. Researchers are excited about duloxetine because it could potentially offer faster relief for both mood and pain symptoms, enhancing the overall recovery experience for patients who have suffered from broken bones.

What is the effectiveness track record for Duloxetine in treating depression after broken bones?

Research has shown that duloxetine effectively treats major depressive disorder (MDD). It improves both emotional and physical pain symptoms in people with depression. In this trial, participants will receive duloxetine, which might be particularly beneficial for patients with bone fractures, as depression often complicates their recovery. While concerns exist about side effects, such as an increased risk of falls, its success in treating depression is well-documented. In summary, duloxetine has a strong track record of aiding depression, which could greatly benefit patients recovering from fractures. ^{1 2 4 6 7}

Who Is on the Research Team?

Rachel Seymour, PhD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for individuals aged 50 and older who have had a lower extremity fragility fracture (a broken bone from a fall at standing height or less) and are managed operatively. It's designed to see if starting an antidepressant, Duloxetine, when they leave the hospital can help prevent depression.

Inclusion Criteria

I am 65 years old or older.

I had surgery for a fragile bone fracture in my leg.

Exclusion Criteria

Polytrauma

I have had a fracture caused by a disease.

Unable to provide informed consent (no use of a legal authorized representative)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants start on Duloxetine 30mg daily at time of discharge and report medication compliance monthly

12 months

Monthly check-ins (virtual or in-person)

Follow-up

Participants complete patient-reported outcome measures at 3 months, 6 months, and 1 year

12 months

3 visits (in-person or virtual)

Referral and Evaluation

Participants receive a referral to behavioral health, primary care, or psychiatrist for evaluation if they screen positive at any timepoint

What Are the Treatments Tested in This Trial?

Interventions

• Duloxetine

Trial Overview The study tests whether prescribing Duloxetine 30 mg daily upon discharge is feasible for these patients. It will also assess depressive symptoms over time using the Geriatric Depression Scale and track medication compliance with monthly re-screening.

How Is the Trial Designed?

Group I: Duloxetine 30mg Experimental Treatment 1 Intervention

Duloxetine 30mg daily 90 day supply and 3 refills

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

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 is an effective treatment for major depressive disorder (MDD), showing significant improvements in both emotional and painful physical symptoms, with noticeable effects after just 1-2 weeks at a dosage of 60 mg per day.

In terms of efficacy, duloxetine is comparable to other antidepressants like paroxetine and escitalopram over both short-term (up to 15 weeks) and longer-term (6-8 months) treatments, and it is generally well tolerated, although starting at 60 mg/day may lead to higher discontinuation rates due to side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine: a review of its use in the treatment of major depressive disorder. Frampton, JE., Plosker, GL.[2018]

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]

In a post-hoc analysis of six trials involving duloxetine for major depressive disorder, significant pain relief was observed within 2 weeks, which occurred faster than the onset of antidepressant effects as measured by the HAMD(17) scale.

The study found that the analgesic effect of duloxetine operates independently from its antidepressant effect, suggesting that the two mechanisms do not influence each other in terms of response time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between antidepressant and analgesic responses: findings from six placebo-controlled trials assessing the efficacy of duloxetine in patients with major depressive disorder. Fishbain, DA., Detke, MJ., Wernicke, J., et al.[2019]

A case report highlights the serious risks associated with high doses of Duloxetine, including acute pulmonary thromboembolism leading to death, particularly in vulnerable populations like the elderly.

Excessive intake of Duloxetine can significantly amplify side effects such as somnolence, dry mouth, and increased blood pressure, emphasizing the importance of adhering to prescribed dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute massive pulmonary thromboembolism due to acute intoxication by duloxetine: a case report. Mari, F., Gualco, B., Rensi, R., et al.[2015]

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]

Duloxetine significantly improved cognitive function, depression, anxiety, pain, and health-related quality of life in older adults with major depressive disorder (MDD) during two 8-week trials, although no significant improvements were noted at the 12-week mark of a longer 24-week trial.

The medication was generally well tolerated, with common side effects including nausea and dizziness, and it had minimal impact on cardiovascular health and body weight, suggesting it is a safe option for older adults with MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine: a review of its use in the management of major depressive disorder in older adults. Dhillon, S.[2021]

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]

Duloxetine has been shown to have a significant direct analgesic effect on painful physical symptoms in patients with major depressive disorder, diabetic peripheral neuropathic pain, and fibromyalgia, with studies indicating that approximately 50% to 90% of the pain relief is due to this direct effect rather than just its antidepressant properties.

In fibromyalgia patients, duloxetine effectively reduces pain regardless of the presence of comorbid depression, highlighting its potential as a pain management option independent of mood improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of duloxetine in painful symptoms: an analgesic or antidepressant effect? Perahia, DG., Pritchett, YL., Desaiah, D., et al.[2015]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7383967/

Multinational Investigation of Fracture Risk with ... Duloxetine, associated with a 41% risk increase, was prescribed to 54.8% of persons with chronic pain compared with 35.3% of persons with depression, whereas ...

2. withpower.com withpower.com/trial/phase-4-fractures-bone-5-2023-b4b16

Duloxetine for Depression after Broken Bones (SNRI Trial) Duloxetine is an effective treatment for major depressive disorder (MDD), showing significant improvements in both emotional and painful physical symptoms, with ...

3. columbiapsychiatry.org columbiapsychiatry.org/news/bone-health-depression-and-its-treatment

Do Antidepressants Increase Risk of Bone Loss? A number of studies have found a link between depression and bone health. Some indicate reduced bone mineral density, accelerated bone loss or ...

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK539626/

Results - Adverse Effects of Pharmacologic Treatments ... - NCBI Duloxetine increased the risk of withdrawal due to adverse events (moderate SOE, NNH 12 [7 to 33]) and the risk of falls (moderate SOE, NNH 10 [6 to 114]) ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223016086

Antidepressant duloxetine hydrochloride protects against ... This study investigates the independent effect of the antidepressant duloxetine hydrochloride (DH) on ovariectomy-induced bone loss in mice.

6. mayoclinic.org mayoclinic.org/drugs-supplements/duloxetine-oral-route/description/drg-20067247

Duloxetine (oral route) - Side effects & dosage Duloxetine is used to treat depression and anxiety. It is also used for pain caused by nerve damage associated with diabetes (diabetic peripheral neuropathy).

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/021427s049lbl.pdf

Label for CYMBALTA (Duloxetine Delayed-Release Capsules) Falls with serious consequences including bone fractures and hospitalizations have been reported [see ... After 7 weeks of treatment with CYMBALTA 60 mg ...