Methadone vs Morphine for Pain After Cesarean Delivery

Overseen By Emily E Sharpe, M.D.

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Must not be taking: Opioids, Antidepressants

Disqualifiers: Chronic pain, Sleep apnea, 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: 0-48 hours

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two pain medications, methadone and morphine, to determine which manages pain better after a scheduled cesarean delivery. The researchers aim to find the necessary dosage of each drug to control pain in the first 48 hours post-surgery. Participants will receive either methadone through an IV or morphine injected into their spine as part of their anesthesia. Women planning a cesarean delivery who speak English may qualify, provided they do not have certain medical conditions or complications with their current pregnancy. As a Phase 4 trial, this research seeks to understand how these FDA-approved medications can benefit more patients effectively.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have a history of chronic pain, opioid use, or certain health conditions, you may not be eligible to participate.

What is the safety track record for these treatments?

Research has shown that methadone is safe for managing pain after a cesarean delivery. Studies indicate that administering methadone through an IV during surgery effectively controls pain without causing serious side effects. In one study, patients who received methadone during their cesarean delivery experienced good pain relief and no major issues.

Morphine is also known to be safe and is commonly used for pain management, including after cesarean deliveries. It works well but can cause mild side effects like nausea or drowsiness, which are usually manageable.

Both treatments have been used safely in similar situations and are considered well-tolerated for this purpose. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they offer new ways to manage pain after a cesarean delivery. Unlike traditional methods that often use intrathecal morphine, one treatment involves intravenous methadone. This approach could potentially provide more consistent pain relief, as methadone has a longer duration of action, which might reduce the need for additional doses. Meanwhile, the use of intrathecal morphine is a well-established option, but the trial compares it directly with methadone to see which is more effective, which could lead to improved pain management strategies for new mothers.

What evidence suggests that this trial's treatments could be effective for pain after cesarean delivery?

Research has shown that methadone, which participants in this trial may receive, effectively relieves pain after a cesarean delivery. Studies have found that methadone provides good pain control and is safe for this purpose. Morphine, another treatment option in this trial, is a well-known choice for managing post-cesarean pain and is often used due to its effectiveness. Both treatments aim to reduce the need for additional pain medications after surgery. This study will determine which option might require fewer extra pain medications. ^{1 3 4 6 7}

Who Is on the Research Team?

Emily E Sharpe, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for English-speaking women over 18 years old scheduled for a cesarean delivery. It's not suitable for those with opioid intolerance, severe obesity (BMI >50), heart issues (QTc >440ms), high-risk health status (ASA IV, V), chronic pain or substance use disorders, liver/kidney failure, certain respiratory conditions, pre-eclampsia in current pregnancy, depression treated with multiple medications, or if general anesthesia becomes necessary.

Inclusion Criteria

English-speaking

Scheduled cesarean delivery

I am over 18 years old.

Exclusion Criteria

BMI >50.0 kg/m2

History of intolerance or adverse reaction to opioid medications

No prior history of an ECG demonstrating QTc > 440ms

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either intrathecal morphine or intravenous methadone for analgesia following cesarean delivery

0-48 hours

In-hospital stay

Follow-up

Participants are monitored for opioid consumption and recovery quality post-treatment

7 days

Daily assessments

What Are the Treatments Tested in This Trial?

Interventions

• Methadone
• Morphine

Trial Overview The study compares post-cesarean pain management between two drugs: intrathecal morphine at 150 mcg and intravenous methadone at 0.2 mg/kg (up to 20 mg). The goal is to see which leads to lower opioid needs within the first 48 hours after surgery.

How Is the Trial Designed?

Group I: Spinal Anesthesia with Intravenous Methadone Experimental Treatment 1 Intervention

Subjects will receive spinal anesthesia (intrathecal bupivacaine with fentanyl) with intravenous methadone

Group II: Spinal Anesthesia with Intrathecal Morphine Active Control 1 Intervention

Subjects will receive spinal anesthesia (intrathecal bupivacaine with fentanyl) with intrathecal morphine

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

A prospective randomized double-blind study found that epidural methadone provided the most effective pain relief after Caesarean sections with minimal side effects.

A subsequent retrospective study of 178 patients confirmed that epidural methadone is both effective and safe for postoperative pain management in Caesarean section patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative analgesia for Caesarean section using epidural methadone. Beeby, D., MacIntosh, KC., Bailey, M., et al.[2019]

In a study of 25 patients receiving intravenous methadone during caesarean delivery, those patients reported lower pain scores and required less additional opioid medication post-surgery compared to a control group of 50 patients.

The use of methadone resulted in significantly lower overall opioid consumption over 48 hours, indicating its effectiveness for pain management with a generally acceptable side-effect profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intraoperative intravenous methadone during general anaesthesia for caesarean delivery: a retrospective case-control study. Russell, T., Mitchell, C., Paech, MJ., et al.[2013]

In a study of 90 women who underwent cesarean delivery, different doses of epidural morphine (2.5, 3, and 4 mg) provided similar levels of pain relief and patient satisfaction, indicating that lower doses can be effective.

Epidural morphine effectively managed pain for about 24 hours post-surgery, with 27% of patients remaining pain-free for up to 48 hours, and no serious complications were reported, although mild side effects like pruritus and nausea were common across all doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of different doses of epidural morphine for pain relief following cesarean section. Chumpathong, S., Santawat, U., Saunya, P., et al.[2013]

Buprenorphine shows better or similar safety outcomes compared to methadone for treating neonatal abstinence syndrome (NAS), with fewer infants requiring treatment and shorter hospital stays, based on a review of 5 critical studies.

Both medications are effective for pregnant women with opioid dependence, but buprenorphine may be a preferable option due to its improved outcomes, although more extensive studies are needed to confirm its safety and advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine Versus Methadone for Opioid Dependence in Pregnancy. Noormohammadi, A., Forinash, A., Yancey, A., et al.[2018]

Methadone is a unique opioid that not only acts on mu receptors but also has effects on delta receptors and NMDA receptors, making it a complex option for pain management, especially in cases of uncontrolled pain or when other opioids cause toxicity.

While methadone can be safer at lower doses, there are significant risks associated with high doses, including prolonged QT interval and potential for serious heart issues, highlighting the need for more research through randomized controlled trials to better understand its safety and efficacy compared to other opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone for treatment of cancer pain. Bryson, J., Tamber, A., Seccareccia, D., et al.[2019]

In a study of 720 women who had cesarean deliveries, it was found that the median number of opioid tablets prescribed was 40, but only 20 were consumed, leaving a significant amount of unused medication.

The research indicates that prescribing fewer opioids does not negatively impact pain control or patient satisfaction, suggesting that current prescribing practices may lead to excess medication and potential safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of Opioid Prescription and Use After Cesarean Delivery. Bateman, BT., Cole, NM., Maeda, A., et al.[2022]

In a study comparing oral methadone and intramuscular pethidine for post-cesarean pain management in women, both medications showed similar effectiveness in reducing pain severity over 24 hours after surgery, indicating that methadone is a viable alternative to pethidine.

Methadone not only provided comparable pain relief but also offered benefits in patient satisfaction and cost-effectiveness, suggesting it could be recommended for routine use in post-operative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain relief after cesarean section: Oral methadone vs. intramuscular pethidine. Shahraki, AD., Jabalameli, M., Ghaedi, S.[2022]

Methadone provided longer-lasting analgesia compared to diamorphine, with a median time to further analgesia of 395 minutes for methadone versus 720 minutes for diamorphine, indicating its potential for better pain management after elective caesarean sections.

While both medications had side effects like nausea and pruritus, methadone was associated with fewer episodes of significant oxygen desaturation compared to diamorphine, suggesting it may be a safer option in terms of respiratory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of epidural methadone with epidural diamorphine for analgesia following caesarean section. Haynes, SR., Davidson, I., Allsop, JR., et al.[2019]

In a study of 72 women undergoing cesarean delivery, a dose of 250 mcg of intrathecal morphine provided significantly longer pain relief (32 hours) compared to lower doses of 150 mcg (29.4 hours) and 50 mcg (24.5 hours), which was found to be inferior in pain management.

The higher doses (150 mcg and 250 mcg) allowed more than half of the patients to remain opioid-free for up to 72 hours, while the 50 mcg group experienced higher pain scores and required more supplemental opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of spinal morphine with an enhanced recovery pathway and its effect on duration of analgesia after cesarean delivery. Borrelli, MC., Sprowell, AJ., Moldysz, A., et al.[2023]

Implementing a standardized, multimodal approach to pain management after cesarean delivery led to a 75% reduction in opioid use, as measured by median morphine milligram equivalents per hospital stay, without increasing pain scores or time to discharge.

The new pain management strategy increased the use of acetaminophen and resulted in a significant rise in the number of patients who used no opioids during their hospital stay, from 6% to 19%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal Stepwise Approach to Reducing In-Hospital Opioid Use After Cesarean Delivery: A Quality Improvement Initiative. Smith, AM., Young, P., Blosser, CC., et al.[2020]

A study involving 109 women after cesarean delivery revealed that they were prescribed significantly more opioid pills than needed, with 63.3% of the prescribed pills remaining unused, indicating a potential over-prescription issue.

Participants reported a correlation between their satisfaction with pain control and the use of fewer opioids, suggesting that personalized discussions about pain management could lead to safer prescribing practices and reduced opioid consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid prescription-use after cesarean delivery: an observational cohort study. Avalos, C., Razzolini, GD., Crimmins, S., et al.[2021]

Women treated with methadone for opiate dependence during pregnancy experience higher pain levels after vaginal and cesarean deliveries compared to control women, with significant increases in pain scores (P=.001).

Despite the increased pain, methadone-maintained women do not show a significant increase in overall opiate use postpartum after vaginal delivery, but they require 70% more opiate analgesics after cesarean delivery (P=.001).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrapartum and postpartum analgesia for women maintained on methadone during pregnancy. Meyer, M., Wagner, K., Benvenuto, A., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7779306/

Post-Cesarean Delivery Analgesic Outcomes in Patients ... One small study of vaginal deliveries showed that women on either buprenorphine or methadone had good pain control and unremarkable opioid ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959289X25003346

Post-cesarean opioid consumption in patients on ... Scheduled multimodal non-opioid analgesics after cesarean delivery are effective in reducing opioid consumption. However, there is limited information ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02091297

Comparison of Different Methods of Pain Control After ... Common ways to treat pain control after Cesarean Section include oral and IV opioids, non-narcotic adjuncts such as non-steroidal anti-inflammatory drugs and ...

4. journals.lww.com journals.lww.com/adbm/fulltext/2014/03000/evaluation_of_the_analgesic_effect_of_subcutaneous.197.aspx

Evaluation of the analgesic effect of subcutaneous... Conclusion: We suggest subcutaneous methadone as a safe pain reliever in post cesarean section patients.

5. liebertpub.com liebertpub.com/doi/10.1089/whr.2022.0108

Pain Management After Cesarean Delivery Among Women ... Previous research does demonstrate that women maintained on buprenorphine can obtain adequate pain control after vaginal and cesarean delivery with analgesic ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959289X12001409

Efficacy and safety of intraoperative intravenous ... Intraoperative intravenous methadone during general anaesthesia was safe and efficacious for caesarean delivery [1386].

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2925397/

Management of Acute Postpartum Pain in Patients ... Further, following cesarean delivery, buprenorphine or methadone treated women showed adequate pain control post-partum using a 24-hour PCA pump followed by ...