Pregabalin vs. Gabapentin for Pain Management

Overseen By John A DeLuca, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: CAMC Health System

Must be taking: Opioids

Must not be taking: Pregabalin, Gabapentin

Disqualifiers: Intubation, Epidural, Brain injury, 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: 7 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Pregabalin or Gabapentin can reduce the need for opioid pain medication in individuals with a single-system orthopedic injury, such as a broken bone. By comparing these two drugs, researchers aim to find a better way to manage pain and reduce opioid use. Patients admitted to the hospital for orthopedic trauma and taking opioids for pain relief may qualify for this study. As a Phase 4 trial, this research involves FDA-approved treatments and seeks to understand their benefits for more patients, offering an opportunity to contribute to improved pain management strategies.

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 pregabalin or gabapentin.

What is the safety track record for Pregabalin and Gabapentin?

A previous study found that pregabalin was generally well-tolerated, but higher doses might cause more side effects, leading some people to stop using it. Pregabalin has been used for over ten years, and most people handle it well, though it can rarely cause muscle problems.

Research has shown that gabapentin is also widely used and has been FDA-approved since 1993. However, a warning exists about possible serious breathing problems with gabapentin. While many people use it safely, there is a risk of breathing issues to consider.

Both medicines have been available for a while, and their safety is well understood. Be aware of possible side effects and consult a healthcare provider when considering these treatments. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using Pregabalin and Gabapentin for pain management because they offer potential advantages over traditional pain medications like opioids and NSAIDs. Pregabalin and Gabapentin are unique because they target calcium channels in the nervous system, which may reduce nerve pain more effectively and with fewer side effects than conventional options. Unlike many pain medications that can cause addiction or stomach issues, these treatments may provide a safer alternative for long-term use. Additionally, the potential for these drugs to address a wide range of pain conditions makes them a promising option in pain management.

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

This trial will compare the effectiveness of pregabalin and gabapentin for pain management. Research has shown that both medications can help manage pain. Participants in the pregabalin arm may find that pregabalin works faster and more effectively than gabapentin for nerve pain, providing significant relief for many. Specifically, among those taking 600 mg of pregabalin daily, about 30% reported their pain was reduced by half or more. Participants in the gabapentin arm may experience moderate pain relief, with 46% experiencing such relief at a dose of 1200 mg daily. Both medications generally outperform a placebo in reducing pain intensity. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults over 18 who have been admitted to a Nurse Practitioner service with single-system orthopedic trauma, need opioids, and will stay in the hospital for more than a day. It's not for those with brain injuries, complex wounds, severe kidney issues, trouble swallowing pills, intubation, epilepsy history or substance use disorder.

Inclusion Criteria

I am currently prescribed opioids.

I expect to stay in the hospital for more than a day after giving consent.

I was admitted to the hospital less than 36 hours ago.

Exclusion Criteria

My kidney function is very low or I am on dialysis.

On Patient Controlled Analgesia (PCA)

I have a history of epilepsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive multiple-dose administrations of Pregabalin or Gabapentin in combination with traditional opioid pain medications

7 days

Daily monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gabapentin
• Pregabalin

Trial Overview

The study compares Pregabalin (50mg) and Gabapentin (300mg) to see if they can help reduce opioid usage when given alongside standard painkillers after orthopedic trauma. Patients are randomly assigned to one of these drugs or no drug at all.

How Is the Trial Designed?

Group I: Pregabalin Experimental Treatment 1 Intervention

Patients will receive 50 mg every 8 hours without dose titration. Patients with CrCl \< 60mL/min will receive same dose given q12 hours. The q12 hour regimen may be increased to q8 hours if CrCl increases above 60mL/min during the 7 days study period or until discharge (if \< 7 days post-enrollment).

Group II: Gabapentin Experimental Treatment 1 Intervention

Patients will receive 300 mg PO every 8 hours without dose titration. Patients with CrCl \< 60mL/min will receive same dose given q12 hours. The q12 hour regimen may be increased to q8 hours if CrCl increases above 60mL/min during the 7 days study period or until discharge (if \< 7 days post-enrollment).

Group III: Neither Pregabalin nor Gabapentin Active Control 1 Intervention

Patients will receive neither Pregabalin nor Gabapentin

Who Is Running the Clinical Trial?

CAMC Health System

Lead Sponsor

Trials

47

Recruited

8,000+

West Virginia Clinical and Translational Science Institute

Collaborator

Trials

8

Recruited

100+

Published Research Related to This Trial

Gabapentin and pregabalin, originally developed for seizures, are now mainly used for pain management, but their FDA-approved uses for pain are quite limited, primarily to specific conditions like postherpetic neuralgia and fibromyalgia.

There is limited evidence supporting the off-label use of gabapentinoids for various pain syndromes, and clinicians should inform patients about the uncertainty of benefits when prescribing these medications for unapproved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Clinical Overview of Off-label Use of Gabapentinoid Drugs. Goodman, CW., Brett, AS.[2020]

In a review of 18 randomized trials involving patients with neuropathic pain, pregabalin showed similar effectiveness in pain relief and sleep interference, regardless of whether patients had previously been treated with gabapentin.

The study suggests that pregabalin can be a suitable treatment option for patients who did not respond well to gabapentin, indicating the importance of personalized treatment strategies for neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pregabalin in Patients with Neuropathic Pain Previously Treated with Gabapentin: A Pooled Analysis of Parallel-Group, Randomized, Placebo-controlled Clinical Trials. Markman, JD., Jensen, TS., Semel, D., et al.[2018]

In a study comparing 44 patients on gabapentin and 88 on pregabalin for chronic peripheral neuropathic pain, pregabalin showed a greater reduction in pain intensity and a higher percentage of patients achieving significant pain relief (60.9% vs 40.5%).

Despite the higher cost of pregabalin, the overall costs related to productivity losses were similar between the two medications, indicating that pregabalin may provide better pain relief without increasing overall treatment costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregabalin and gabapentin in matched patients with peripheral neuropathic pain in routine medical practice in a primary care setting: Findings from a cost-consequences analysis in a nested case-control study. Pérez, C., Navarro, A., Saldaña, MT., et al.[2018]

In a study of 64 patients with moderate to severe low back pain, pregabalin (300 mg/day) was found to significantly reduce pain intensity compared to gabapentin (800 mg/day), indicating its potential superiority in pain management.

Gabapentin showed greater improvements in secondary symptoms such as anxiety, insomnia, and fatigue compared to pregabalin, suggesting that while pregabalin is better for pain relief, gabapentin may be more beneficial for overall well-being in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Difference between Gabapentin and Pregabalin: Data from a Pilot Comparative Trial. Gammoh, O., Al-Smadi, A., Shawagfeh, MQ., et al.[2021]

Gabapentin and pregabalin, both used for neuropathic pain, can be combined effectively without significant drug interactions, potentially enhancing pain control while allowing for lower doses of each medication.

This combination therapy may help reduce side effects and improve therapeutic responses, but careful consideration of pharmacokinetics and patient tolerance is necessary before recommending it as a first-line treatment for difficult pain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for combined use of gabapentin and pregabalin in pain control? Too good to be true? Senderovich, H., Jeyapragasan, G.[2019]

A safety study conducted by the Medicines and Healthcare products Regulatory Agency (MHRA) evaluated the risks associated with the use of pregabalin (Lyrica) during pregnancy, highlighting potential safety concerns for pregnant individuals.

The findings emphasize the importance of careful consideration and monitoring when prescribing pregabalin to pregnant patients, as the study aims to inform healthcare providers about the risks involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety update: pregabalin during pregnancy. [2022]

In a study of 252 patients, gabapentin and pregabalin showed no significant difference in pain reduction after six months, indicating both are similarly effective for neuropathic pain.

However, pregabalin was associated with fewer dose reductions due to side effects and required fewer pills per day compared to gabapentin, suggesting it may be better tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing Effectiveness of Gabapentin and Pregabalin in Treatment of Neuropathic Pain: A Retrospective Cohort of Palliative Care Outpatients. Dragic, L., Webb, T., Chandler, M., et al.[2021]

Substituting pregabalin (PGB) for gabapentin (GBP) in patients with peripheral neuropathy resulted in an additional 25% relief of neuropathic pain after 6 and 12 months, indicating PGB may be more effective for some patients.

While there were no serious adverse events reported, over 30% of GBP nonresponders discontinued PGB due to inefficacy or side effects, highlighting the need for careful monitoring when switching medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Substitution of gabapentin therapy with pregabalin therapy in neuropathic pain due to peripheral neuropathy. Toth, C.[2022]

Pregabalin is significantly more potent than gabapentin in treating visceral pain, with an effective dose (ED50) of 17.1 mg/kg compared to gabapentin's 87.1 mg/kg, indicating it may be a more effective option for pain management.

While pregabalin is more effective than gabapentin, it is still much less potent than morphine, which has an ED50 of only 0.2 mg/kg, suggesting that while pregabalin is a strong analgesic, morphine remains the most powerful option in this model of pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain. Shamsi Meymandi, M., Keyhanfar, F.[2018]

In a study of 3,894 patients (1,650 new users of mirogabalin and 2,244 new users of pregabalin), no serious safety concerns were identified for either medication in treating neuropathic pain.

However, mirogabalin users showed a higher hazard ratio for several common adverse events, such as nausea (2.8) and edema (3.1), suggesting a potentially increased risk compared to pregabalin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of mirogabalin and pregabalin in Japanese patients with neuropathic pain: a retrospective cohort study. Nakajima, R., Ooba, N., Kamei, M., et al.[2023]

A total of 1333 adverse drug reactions (ADRs) were reported for gabapentin and pregabalin, with a significant prevalence of neuropsychiatric ADRs, highlighting the need for careful monitoring of these medications.

The study identified serious concerns, including 22 deaths associated with these drugs, particularly noting 8 deaths related to gabapentin in obstetrical situations, and new ADRs such as hepatitis linked to gabapentin and hematological issues with pregabalin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions to gabapentin and pregabalin: a review of the French pharmacovigilance database. Fuzier, R., Serres, I., Guitton, E., et al.[2021]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/28597471/

Gabapentin for chronic neuropathic pain in adults

More participants (46%) had moderate benefit (at least 30% pain relief or PGIC much or very much improved) with gabapentin at 1200 mg daily or ...

2.

frontiersin.org

frontiersin.org/journals/pain-research/articles/10.3389/fpain.2024.1513597/full

Pregabalin vs. gabapentin in the treatment of neuropathic ...

Conclusion: In conclusion, pregabalin demonstrated superior and faster efficacy in alleviating neuropathic pain than gabapentin did.

3.

aafp.org

aafp.org/pubs/afp/issues/2019/1201/p672.html

Gabapentinoids for Pain: Potential Unintended ... - AAFP

Note: Positive trials indicate that gabapentinoids were superior to placebo in pain relief. Because the primary outcome in most studies was ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10250255/

The safety and efficacy of gabapentinoids in the management ...

We found that pregabalin and gabapentin were more efficacious than placebo (≥ 30% and ≥ 50% pain intensity reduction). The NNTs of pregabalin ...

5.

ti.ubc.ca

ti.ubc.ca/2009/12/31/gabapentin-for-pain-new-evidence-from-hidden-data/

[75] Gabapentin for pain: New evidence from hidden data

3 trials (N=1028) assessed percentage of patients achieving at least a 50% reduction in pain score: gabapentin 31.4%, placebo 18.4%; difference ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2017/020235s064_020882s047_021129s046lbl.pdf

NEURONTIN (gabapentin) - accessdata.fda.gov

Safety and effectiveness of NEURONTIN in the management of postherpetic neuralgia in pediatric patients have not been established. Safety and effectiveness as ...

7.

mayoclinic.org

mayoclinic.org/drugs-supplements/gabapentin-oral-route/description/drg-20064011

Gabapentin (oral route) - Side effects & dosage

However, safety and efficacy have not been established in children younger than 3 years of age. Appropriate studies have not been performed on ...

8.

drugs.com

drugs.com/gabapentin.html

Gabapentin: Uses, Dosage, Side Effects, Warnings

Yes, Gabapentin is safe for cats when prescribed by a veterinarian. This medication is commonly used to treat cat pain, anxiety, and feline ...

9.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK493228/

Gabapentin - StatPearls - NCBI Bookshelf - NIH

Gabapentin is an anticonvulsive medication that received approval from the US Food and Drug Administration (FDA) in 1993 and has been available in generic form ...

10.

fda.gov

fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin

Serious breathing difficulties with gabapentin and pregabalin

The US Food and Drug Administration (FDA) is warning that serious breathing difficulties may occur in patients using gabapentin (Neurontin, Gralise, Horizant) ...