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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two medications, duloxetine and desipramine, to determine which more effectively reduces chronic pain. Chronic pain affects millions and has limited treatment options, so this research could improve patient care. Participants will take either duloxetine or desipramine, starting with a low dose and increasing as tolerated, over six months. Individuals with persistent pain for more than three months who are suitable for antidepressant treatment might be a good fit. The study aims to identify which medication alleviates pain more effectively and which one patients adhere to better. As a Phase 4 trial, this research involves FDA-approved treatments and seeks to understand how these medications can benefit a broader range of patients.

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 is the safety track record for these treatments?

Research has shown that duloxetine is generally well-tolerated. It often treats depression, anxiety, and nerve pain, such as diabetic neuropathy. Most people experience mild side effects, like nausea or dry mouth, while serious side effects are rare.

Desipramine, however, has raised some concerns. Studies have found that it often causes more side effects, such as dizziness or a faster heartbeat. There is also a higher likelihood of patients discontinuing treatment early due to these side effects.

Both duloxetine and desipramine manage pain, but duloxetine might be the safer choice. It is approved for more pain conditions and tends to have milder side effects compared to desipramine. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Duloxetine and Desipramine for chronic pain because they offer unique approaches compared to the standard treatments like NSAIDs and opioids. Duloxetine is an SNRI (serotonin-norepinephrine reuptake inhibitor) that not only helps with pain but also addresses mood disorders, which are often linked to chronic pain. Desipramine, a tricyclic antidepressant, works by altering neurotransmitter levels to reduce pain perception. These treatments provide alternative options that might manage pain with potentially fewer side effects than traditional painkillers.

What evidence suggests that this trial's treatments could be effective for chronic pain?

This trial will compare Duloxetine and Desipramine for chronic pain. Research shows that Duloxetine can effectively reduce pain, particularly in conditions like diabetic nerve pain and long-term muscle and bone pain. Studies have found that 45.6% of patients experience their pain cut in half, and 64.5% see at least a 30% reduction in pain. Additionally, Duloxetine can also help with depression and anxiety, which often accompany chronic pain.

In contrast, Desipramine has less evidence supporting its use for nerve pain relief. Some studies suggest it might slightly help with pain, but the evidence is not very strong. In some cases, patients reported moderate pain relief after using Desipramine for several weeks. Overall, Duloxetine appears to have stronger support for effectively managing chronic pain. ^{1 6 7 8 9}

Who Is on the Research Team?

Vafi Salmasi, MD.

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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 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, 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]

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]

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 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]

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, 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6804291/

Desipramine for neuropathic pain in adults - PMC This review found little evidence to support the use of desipramine to treat neuropathic pain. There was very low quality evidence of benefit and harm, but this ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03548454?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(NORPRAMIN))&rank=8

Comparing Effectiveness of Duloxetine and Desipramine in ... Comparing Effectiveness of Duloxetine and Desipramine in Patients With Chronic Pain: A Pragmatic Trial Using Point of Care Randomization ; ClinicalTrials.gov ID ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25246131/

Desipramine for neuropathic pain in adults This review found little evidence to support the use of desipramine to treat neuropathic pain. There was very low quality evidence of ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/14651858.CD011003.pub2/abstract

Desipramine for neuropathic pain in adults - Hearn, L - 2014 No pooling of data was possible, but third tier evidence in individual studies indicated some improvement in pain relief with desipramine ...

5. journals.lww.com journals.lww.com/pain/abstract/1991/04000/efficacy_of_desipramine_in_painful_diabetic.2.aspx

Efficacy of desipramine in painful diabetic neuropathy Pain relief with desipramine was statistically significant in weeks 5 and 6. Eleven patients reported at least moderate relief with desipramine, compared to 2 ...

6. researchgate.net researchgate.net/publication/283489332_Desipramine_for_neuropathic_pain_in_adults

(PDF) Desipramine for neuropathic pain in adults Participants taking desipramine experienced more adverse events, and a higher rate of withdrawal due to adverse events, than did participants ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03548454?term=AREA%5BBasicSearch%5D(NORPRAMIN)&rank=8

Comparing Effectiveness of Duloxetine and Desipramine in ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

8. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2017.00307/full

Adverse Effects of Antidepressants for Chronic Pain Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82]) followed by milnacipran, ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9887507/

Efficacy, safety, and tolerability of antidepressants for pain in ... To provide a comprehensive overview of the efficacy, safety, and tolerability of antidepressants for pain according to condition.