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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients experience pain after their knee replacement surgery - and some may continue to experience persistent pain long after their knee replacement surgery. Traditional pain management strategies reply on pain medication such as opioids for pain control. However, these drugs do not work well for pain associated with movement or the the nerve pain (tingling, electrical sensations) after surgery. In addition, opioids are associated with significant side effects such as nausea, vomiting, respiratory depression, depression, cognitive dysfunction and risk of persistent opioid use. Neuropathic pain medications, such as venlafaxine are effective in managing nerve pain. Recent studies also support its potential role in acute pain management. Here, we propose a prospective randomized clinical trial 1) to evaluate the efficacy of Venlafaxine in reducing pain intensity and opioid consumption at post-operative day 1 (POD1) and 1- week after surgery, and 2) to examine whether the use of Venlafaxine will reduce the incidents of chronic postsurgical pain in TKA patients at 3-month time point.

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.

Is venlafaxine safe for humans?

Venlafaxine has been shown to be generally safe and well-tolerated in humans, with common side effects including nausea, headache, and dizziness. Serious adverse events are rare, and its safety profile is similar to other modern antidepressants. ^{1 2 3 4 5}

How is the drug venlafaxine unique for treating knee pain?

Venlafaxine is unique for treating knee pain because it is primarily an antidepressant that also has pain-relieving properties, particularly for neuropathic and inflammatory pain, which is not typical for most knee pain treatments. It works by affecting neurotransmitters (chemical messengers in the brain) like serotonin and noradrenaline, which can help manage pain and mood. ^{2 6 7 8 9}

Research Team

Matthias Behrends, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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 between 18 and 75 years old.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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 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]

References

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

The safety and tolerability of venlafaxine hydrochloride: analysis of the clinical trials database. [2022]

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

Venlafaxine hydrochloride (Effexor) relieves thermal hyperalgesia in rats with an experimental mononeuropathy. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Safety and tolerance profile of venlafaxine. [2019]

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

Efficacy of venlafaxine for the long term treatment of chronic pain with associated major depressive disorder. [2022]

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

Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. [2022]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Results of a study of velaxin (venlafaxine) efficacy in patients with subacute and chronic spondylogenic dorsalgia]. [2022]

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

Venlafaxine-tramadol similarities. [2019]

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

Protection against oxaliplatin acute neurosensory toxicity by venlafaxine. [2019]

9. Turkey pubmed.ncbi.nlm.nih.gov

Evaluation of antinociceptive and anti-inflammatory effects of venlafaxine in the rat. [2022]