Duloxetine vs Desipramine for Chronic Pain

Overseen By Vafi Salmasi, MD.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Stanford University

Must be taking: Antidepressants

Disqualifiers: Prior failure duloxetine, desipramine, 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: Unknown

Duration: 6 months

320 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug duloxetine for chronic pain?

Duloxetine has been shown to be effective in relieving pain associated with major depressive disorder and diabetic peripheral neuropathic pain, and it is also used for fibromyalgia, which involves chronic pain. This suggests it may help with chronic pain, although more research is needed to confirm its effectiveness specifically for chronic pain conditions. ^{1 2 3 4 5}

What safety data exists for duloxetine and desipramine in humans?

Duloxetine has been studied for safety in various conditions, including major depressive disorder, diabetic peripheral neuropathic pain, and fibromyalgia. Common side effects include nausea, headache, dry mouth, insomnia, fatigue, constipation, diarrhea, and dizziness. There is no specific safety data provided for desipramine in the research articles. ^{4 6 7 8 9}

How does the drug duloxetine differ from other treatments for chronic pain?

Duloxetine is unique because it works by directly affecting pain pathways in the brain, providing both pain relief and antidepressant effects, which is beneficial for conditions like fibromyalgia and diabetic neuropathic pain. It is a selective serotonin and norepinephrine reuptake inhibitor (SSNRI), which means it increases the levels of these neurotransmitters to help reduce pain and improve mood. ^{10 11 12 13 14}

What is the purpose of this trial?

Over 100 million Americans suffer from chronic pain resulting in annual cost of roughly $635 billion. Limited treatments are available for this widespread disease. The data supporting these treatments lack generalizability to patients with more serious medical and psychological comorbidities who are often excluded from explanatory efficacy trials. Our work aims to integrate randomized comparative effectiveness research with patient care. The investigators will randomize the patients and collect data using an open-source learning healthcare system already in use in our department to monitor patients' progress: Collaborative Health Outcomes Information Registry (CHOIR). Collaborative Health Outcomes Information Registry uses the National Institute of Health Patient Reported Outcomes Measurement Information System item banks for comparative metrics through computer adaptive testing. The investigators will leverage the advantage of this novel system to compare effectiveness of duloxetine and desipramine in decreasing pain in patients with chronic pain. The investigators will also compare adherence of patients to these two commonly used medications over a period of six months. This will evaluate feasibility of integrating randomized comparative effectiveness research with patient care in subspecialty clinics. Collaborative Health Outcomes Information Registry can then be applied for numerous future trials to advance our knowledge in perioperative and pain medicine.

Research Team

Vafi Salmasi, MD.

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults over 18 with chronic pain lasting more than 3 months who could benefit from antidepressant treatment. It's not for those who've previously had no success with Duloxetine or Desipramine, have conditions that make these drugs unsafe, or choose not to participate.

Inclusion Criteria

I have had pain for over 3 months.

My doctor thinks I should take antidepressants for my pain.

Exclusion Criteria

I have tried duloxetine or desipramine for my condition without success.

I cannot take duloxetine or desipramine due to health reasons.

I have chosen not to participate in this trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either duloxetine or desipramine, with dosages adjusted as tolerated, to assess effectiveness in decreasing pain

6 months

Monthly assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Desipramine
• Duloxetine

Trial Overview The study compares the effectiveness of two medications, Duloxetine and Desipramine, in reducing chronic pain. Patients will be randomly assigned a medication and monitored using an online system (CHOIR) to track their progress over six months.

Participant Groups

Group I: Duloxetine Experimental Treatment 1 Intervention

Duloxetine starting at 20 mg per day and increasing to 60 mg per day as tolerated.

Group II: Desipramine Experimental Treatment 1 Intervention

Desipramine starting at 25 mg per day and increasing to 75 mg per day as tolerated.

Desipramine is already approved in United States for the following indications:

Approved in United States as Desipramine for:

• Depression
• Irritable Bowel Syndrome
• ADHD
• Dysautonomia
• Vulvodynia

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

In a study of 622 adult outpatients treated with duloxetine for depression, patients experienced a significant improvement in pain symptoms earlier than mood symptoms, with a mean time to 50% pain response of 6.3 days compared to 7.6 days for mood response.

This finding suggests that duloxetine may provide quicker relief from physical pain associated with depression, which could be important for treatment strategies focusing on both emotional and physical symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does pain improve earlier than mood in depressed patients with painful physical symptoms treated with duloxetine? Hegerl, U., Mergl, R., Quail, D., et al.[2015]

Duloxetine, a new antidepressant, has shown potential for pain management due to its effects on both noradrenergic and serotonergic neurotransmitters, as indicated by preclinical studies.

While it may help alleviate pain in patients with major depression, its effectiveness for treating pain disorders in general is not yet established, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressant Use in Chronic Pain Management: Is There Evidence of a Role for Duloxetine? Leo, RJ., Barkin, RL.[2020]

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]

Duloxetine, at a dose of 60 mg/day, was found to be significantly more effective than placebo in treating major depressive disorder (MDD) in patients aged 55 and older, with a remission rate of 44.1% compared to 16.1% for placebo.

In addition to improving depressive symptoms, duloxetine also significantly reduced pain symptoms, including overall pain and back pain, although it had a higher discontinuation rate due to adverse events (21.0% for duloxetine vs. 6.7% for placebo).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine for the treatment of major depressive disorder in older patients. Nelson, JC., Wohlreich, MM., Mallinckrodt, CH., et al.[2022]

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 hydrochloride, at a fixed dose of 60 mg twice daily, was found to be safe and well tolerated over a 52-week period for patients with diabetic peripheral neuropathic pain (DPNP), showing no significant adverse effects compared to routine care.

Patients receiving routine care experienced a higher rate of serious adverse events, while duloxetine did not negatively impact glycemic control, lipid profiles, or nerve function, indicating its potential as an effective long-term treatment option for DPNP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine versus routine care in the long-term management of diabetic peripheral neuropathic pain. Raskin, J., Smith, TR., Wong, K., et al.[2022]

Duloxetine at a fixed dose of 60 mg twice daily is safe for long-term use (up to 52 weeks) in managing diabetic peripheral neuropathic pain (DPNP), with no significant differences in serious adverse events compared to routine care.

Patients treated with duloxetine showed significant improvements in quality of life measures, including physical functioning and pain relief, while experiencing a higher incidence of asthenia, but no adverse effects on lipid profiles or nerve function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label 52-week clinical extension comparing duloxetine with routine care in patients with diabetic peripheral neuropathic pain. Wernicke, JF., Wang, F., Pritchett, YL., et al.[2022]

Duloxetine is an effective treatment option for major depression and diabetic peripheral neuropathic pain, functioning as a serotonin and norepinephrine reuptake inhibitor.

Additionally, duloxetine is approved for treating moderate to severe stress urinary incontinence in women, highlighting its versatility across different medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a place for duloxetine? [2022]

Duloxetine treatment for fibromyalgia has a generally safe profile, with the most common mild to moderate side effects being nausea (29.3%), headache (20.0%), and dry mouth (18.2%), observed in short-term studies involving multiple patients.

Long-term use of duloxetine (up to 1 year) showed a similar safety profile to short-term use, with no new significant adverse events emerging, and serious adverse events were rare, indicating that duloxetine can be a viable long-term treatment option for fibromyalgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of duloxetine in the treatment of patients with fibromyalgia: pooled analysis of data from five clinical trials. Choy, EH., Mease, PJ., Kajdasz, DK., et al.[2021]

In a study involving 58 patients with painful diabetic neuropathy, both duloxetine and amitriptyline were found to significantly reduce pain levels, with 55% of patients achieving good pain relief on amitriptyline and 59% on duloxetine.

Duloxetine was associated with fewer adverse effects, particularly dry mouth, which occurred in 55% of patients taking amitriptyline compared to only 24% for duloxetine, suggesting it may be a safer option for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative evaluation of amitriptyline and duloxetine in painful diabetic neuropathy: a randomized, double-blind, cross-over clinical trial. Kaur, H., Hota, D., Bhansali, A., et al.[2022]

In two phase III studies, duloxetine 60 mg/day significantly reduced average pain severity and improved patient-reported outcomes in fibromyalgia patients compared to placebo, demonstrating its efficacy in managing pain.

Despite initial improvements, a longer 27-week trial showed no significant difference between duloxetine and placebo for pain scores, and increasing the dose to 120 mg/day did not enhance response in nonresponders, indicating a limit to its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine: in patients with fibromyalgia. Curran, MP.[2021]

Duloxetine and nortriptyline both significantly reduced diabetic neuropathic pain compared to placebo, with duloxetine showing a reduction in pain intensity from 6.4 to 3.75 on the visual analogue scale (VAS).

There was no significant difference in pain relief efficacy between duloxetine and nortriptyline, indicating that both medications are effective and safe options for managing diabetic neuropathic pain without serious adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic effect of duloxetine compared to nortryptiline in patients with painful neuropathy: A randomized, double-blind, placebo-controlled trial. Mohammadali Bayani, M., Moazammi, B., Fadaee-Jouybari, F., 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]

Duloxetine, at a dosage of 60 mg once daily, has been shown to be effective in managing chronic pain conditions such as diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain associated with osteoarthritis and low back pain, based on a review of 30 clinical studies.

The medication's dual action on serotonin and norepinephrine reuptake may make it a versatile treatment option for patients who experience both chronic pain and comorbid conditions like major depressive disorder or generalized anxiety disorder, provided that safety guidelines are followed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of duloxetine 60 mg once-daily dosing for the management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic osteoarthritis pain and low back pain. Pergolizzi, JV., Raffa, RB., Taylor, R., et al.[2015]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Does pain improve earlier than mood in depressed patients with painful physical symptoms treated with duloxetine? [2015]

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

Antidepressant Use in Chronic Pain Management: Is There Evidence of a Role for Duloxetine? [2020]

3. England 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. [2019]

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

Duloxetine for the treatment of major depressive disorder in older patients. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Duloxetine versus routine care in the long-term management of diabetic peripheral neuropathic pain. [2022]

7. England pubmed.ncbi.nlm.nih.gov

An open-label 52-week clinical extension comparing duloxetine with routine care in patients with diabetic peripheral neuropathic pain. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Is there a place for duloxetine? [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of duloxetine in the treatment of patients with fibromyalgia: pooled analysis of data from five clinical trials. [2021]

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

A comparative evaluation of amitriptyline and duloxetine in painful diabetic neuropathy: a randomized, double-blind, cross-over clinical trial. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Duloxetine: in patients with fibromyalgia. [2021]

12. Iran pubmed.ncbi.nlm.nih.gov

Analgesic effect of duloxetine compared to nortryptiline in patients with painful neuropathy: A randomized, double-blind, placebo-controlled trial. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Efficacy of duloxetine in painful symptoms: an analgesic or antidepressant effect? [2015]

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

A review of duloxetine 60 mg once-daily dosing for the management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic osteoarthritis pain and low back pain. [2015]