Venlafaxine for Knee Pain

Overseen By Matthias Behrends, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Must not be taking: Antidepressants, Triptans, Linezolid, Benzodiazepines

Disqualifiers: General anesthesia, Chronic opioid use, others

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: Unknown

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if venlafaxine, a medication typically used for nerve pain, can reduce pain and the need for opioids after knee replacement surgery. Researchers seek to discover if it can also decrease the likelihood of long-term pain following the procedure. Participants will receive either venlafaxine or a placebo (a harmless pill with no active drug) for seven days, starting on the day of their surgery. The trial seeks individuals scheduled for knee replacement surgery with spinal anesthesia and a specific type of nerve block. As a Phase 4 trial, this research focuses on understanding how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

You may need to stop taking certain medications. The trial excludes people who are currently using antidepressants, triptans, linezolid, or benzodiazepines.

What is the safety track record for Venlafaxine?

Research has shown that venlafaxine is generally safe and well-tolerated. Data from 19 studies involving 2,181 patients indicate its safety for those with major depression. However, studies on using antidepressants like venlafaxine for conditions such as hip and knee osteoarthritis have reported more side effects. Specifically, 64% of people taking antidepressants experienced side effects compared to 49% in the placebo group. This suggests that while venlafaxine can be effective, it might cause more side effects than a placebo. Discussing these potential risks with a healthcare provider before joining a trial is advisable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Venlafaxine is unique because it's typically used as an antidepressant but is now being explored for knee pain relief. Unlike standard treatments for knee pain, which often include NSAIDs like ibuprofen or acetaminophen, venlafaxine works differently by targeting serotonin and norepinephrine pathways in the brain. Researchers are excited about this approach because it could offer pain relief without the gastrointestinal side effects common in many traditional pain medications. Additionally, venlafaxine has the potential to provide rapid pain reduction, with effects possibly noticeable within just a few days.

What is the effectiveness track record for Venlafaxine in managing knee pain after surgery?

Research has shown that venlafaxine, a medication often used for nerve pain, might help with pain after knee surgery. In this trial, participants in the venlafaxine arm will take 37.5mg of venlafaxine daily for 7 consecutive days, starting on the day of primary arthroplasty surgery. One study found that patients using venlafaxine for osteoarthritis pain experienced a 25% reduction in average pain levels, suggesting its effectiveness for managing pain after knee replacement surgery. Additionally, venlafaxine may reduce the need for opioids, which can cause many side effects. It has already shown promise for managing nerve-related pain, which is common after surgery. ^{1 2 4 5 6}

Who Is on the Research Team?

Matthias Behrends, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 18 to 75 who are scheduled for primary total knee replacement surgery with specific anesthesia. It's not for those on antidepressants, triptans, or linezolid; with allergies to study meds; BMI over 40; prior knee surgery; recent falls; liver/renal failure; bleeding disorders; general anesthesia use; diabetic nerve pain history or chronic opioid/benzodiazepine users.

Inclusion Criteria

English speaking

I am scheduled for a knee replacement surgery with specific anesthesia and nerve block.

Exclusion Criteria

I have a bleeding disorder.

Chronic opioid use

Allergy to the study medications

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Venlafaxine 37.5 mg/d or a placebo starting on the day of surgery and continue for 7 days

1 week

Daily administration

Follow-up

Participants are monitored for pain severity, opioid consumption, and functionality at 7 days and 3 months post-surgery

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Venlafaxine

Trial Overview The trial tests if Venlafaxine (37.5 MG) can reduce pain and opioid use after knee replacement compared to a placebo. The focus is on the first day post-op and one week later, plus checking if it lowers long-term chronic pain at three months.

How Is the Trial Designed?

Group I: Venlafaxine Experimental Treatment 1 Intervention

Subjects in venlafaxine arm will receive venlafaxine 37.5mg daily for 7 consecutive days starting on day of primary arthroplasty surgery.

Group II: Placebo Placebo Group 1 Intervention

Subjects in placebo arm will receive inactive placebo capsule daily for 7 consecutive days starting on day of primary arthroplasty surgery.

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

Approved in European Union as Efexor for:

• Major depressive disorder
• Generalized anxiety disorder
• Social anxiety disorder
• Panic disorder

Approved in United States as Effexor for:

• Major depressive disorder
• Generalized anxiety disorder
• Social anxiety disorder
• Panic disorder

Approved in Canada as Effexor for:

• Major depressive disorder
• Generalized anxiety disorder
• Social anxiety disorder
• Panic disorder

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Orthopedic Research and Education Foundation

Collaborator

Trials

23

Recruited

6,200+

Published Research Related to This Trial

In a study of 47 patients with spondylogenic dorsopathy, velaxin (venlafaxine) significantly reduced pain intensity and activity restriction over 8 weeks, with 85% of patients experiencing a 50% reduction in pain.

The treatment was well-tolerated, with no serious side effects reported, indicating that velaxin is a safe and effective option for managing chronic pain in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of a study of velaxin (venlafaxine) efficacy in patients with subacute and chronic spondylogenic dorsalgia]. Batysheva, TT., Kamchatnov, PR., Guseva, ME., et al.[2022]

In a study involving 24 male rats with neuropathic pain, venlafaxine effectively prevented the development of thermal hyperalgesia, demonstrating its potential as a pain relief option without the sedative effects seen in other treatments.

Venlafaxine not only reversed existing thermal hyperalgesia in rats with established neuropathic pain but also showed a mild non-specific analgesic effect, indicating its efficacy in managing pain without significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venlafaxine hydrochloride (Effexor) relieves thermal hyperalgesia in rats with an experimental mononeuropathy. Lang, E., Hord, HA., Denson, D.[2022]

A single oral dose of 50 mg venlafaxine given at the start of oxaliplatin infusion significantly reduced acute neurosensory symptoms, such as paresthesias, in patients.

The results were consistent and dramatic, suggesting that venlafaxine could be an effective option for managing oxaliplatin-related neurosensory toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protection against oxaliplatin acute neurosensory toxicity by venlafaxine. Durand, JP., Brezault, C., Goldwasser, F.[2019]

Venlafaxine hydrochloride, a serotonin and norepinephrine reuptake inhibitor, was found to have a tolerability and safety profile similar to selective serotonin reuptake inhibitors, based on data from 3,082 patients, with most experiencing manageable side effects like nausea and insomnia.

Serious adverse events were rare, and while a small percentage of patients experienced modest increases in blood pressure, these were comparable to those seen with other antidepressants, indicating that venlafaxine is generally safe for both younger and older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and tolerability of venlafaxine hydrochloride: analysis of the clinical trials database. Rudolph, RL., Derivan, AT.[2022]

Venlafaxine significantly reduced pain sensitivity and inflammation in rats with carrageenan-induced pain, demonstrating its antinociceptive properties.

The study showed that pretreatment with venlafaxine effectively alleviated mechanical hypersensitivity and reduced paw edema, indicating its potential as a treatment for inflammatory pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of antinociceptive and anti-inflammatory effects of venlafaxine in the rat. Aricioğlu, F., Buldanlioğlu, U., Salanturoğlu, G., et al.[2022]

In a 1-year open-label study involving outpatients with major depressive disorder (MDD) who had previously failed other treatments, venlafaxine extended release (XR) significantly improved depression, pain, and quality of life scores.

Venlafaxine XR works as a reuptake inhibitor for serotonin, norepinephrine, and dopamine, demonstrating both antidepressant and analgesic properties, making it effective for patients with chronic pain and depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of venlafaxine for the long term treatment of chronic pain with associated major depressive disorder. Bradley, RH., Barkin, RL., Jerome, J., et al.[2022]

Venlafaxine and tramadol have similar molecular and pharmacological properties, suggesting they may be effective for treating both depression and pain.

Patients suffering from both depression and pain could benefit from using either venlafaxine or tramadol as a single treatment option, potentially simplifying their therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venlafaxine-tramadol similarities. Markowitz, JS., Patrick, KS.[2019]

Venlafaxine is safe and well tolerated in patients with major depression, based on data from 19 studies involving 2181 patients, with a long-term safety evaluation in 422 patients treated for at least one year.

The adverse events associated with venlafaxine, such as nausea and headache, were common but comparable to those seen with third-generation antidepressants, and venlafaxine had a lower frequency of anticholinergic events compared to first-generation antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerance profile of venlafaxine. Danjou, P., Hackett, D.[2019]

In a study of 244 patients with painful diabetic neuropathy, venlafaxine extended-release (ER) at doses of 150-225 mg significantly reduced pain intensity by 50% compared to placebo after 6 weeks, demonstrating its efficacy in pain relief.

The treatment was generally safe, with nausea and somnolence being the most common side effects, and the number needed to treat (NNT) for achieving a 50% reduction in pain was 4.5, indicating a favorable response rate similar to other established treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Rowbotham, MC., Goli, V., Kunz, NR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10496098/

Preoperative anxiolytic and antidepressant medications as ... The use of chronic anxiolytics or antidepressants was associated with increased opioid use and slightly higher pain scores in patients undergoing TKA.

2. arthroplastyjournal.org arthroplastyjournal.org/article/S0883-5403(24)00136-0/fulltext

Results of Primary Total Knee Arthroplasty in Patients on ... The aim of this study was to determine the impact of psychotropic medications in patients undergoing primary total knee arthroplasty (TKA)

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05023278/the-use-of-venlafaxine-in-reducing-pain-in-primary-total-knee-replacement

The Use of Venlafaxine in Reducing Pain in Primary Total ... Here, we propose a prospective randomized clinical trial 1) to evaluate the efficacy of Venlafaxine in reducing pain intensity and opioid ...

4. academic.oup.com academic.oup.com/painmedicine/article/10/5/806/1825694

Single-Blind Placebo Run-In Study of Venlafaxine XR for ... In this study, 10 weeks of venlafaxine treatment for osteoarthritis pain (following 2 weeks of placebo treatment) yielded a 25% reduction (P = 0.03) of average ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9586196/

Antidepressants for hip and knee osteoarthritis - PMC Data collection and analysis. We used standard Cochrane methods. Major outcomes were pain; responder rate; physical function; quality of life; and proportion of ...

6. withpower.com withpower.com/trial/phase-4-neuralgia-4-2021-5ce53

Venlafaxine for Knee Pain · Info for Participants Venlafaxine is safe and well tolerated in patients with major depression, based on data from 19 studies involving 2181 patients, with a long-term safety ...