A Preliminary Study Comparing Methadone and Buprenorphine in Patients with Chronic Pain and Coexistent Opioid Addiction
Open accessAbstract
Patients with opioid addiction who receive prescription opioids for treatment of nonmalignant chronic pain present a therapeutic challenge. Fifty-four participants with chronic pain and opioid addiction were randomized to receive methadone or buprenorphine/naloxone. At the 6-month follow-up examination, 26 (48.1%) participants who remained in the study noted a 12.75% reduction in pain (P = 0.043), and no participants in the methadone group compared to 5 in the buprenorphine group reported illicit opioid use (P = 0.039). Other differences between the two conditions were not found. Long-term, low-dose methadone or buprenorphine/naloxone treatment produced analgesia in participants with chronic pain and opioid addiction.
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Claims the paper makes
0 of 28 cited sources checked · 0 supported · 0 flagged
- Findingown data
Across both treatment groups, participants reported significantly less pain at six months than at the initial visit, with a 12.75% reduction in pain (P = 0.043).
“Across both treatment condition, participants reported significantly less pain at 6 months (M = 5.5, SD = 1.9) than at the initial visit (M = 6.3, SD = 1.2) with a 12.75% reduction in pain at medium effect size (Cohen’s d = 0.52).”
Quote in the paperSubstantial claim - Findingown data
Only 21 participants reported using opiates at the initial visit, despite all having a diagnosis of opioid dependence.
“Although all patients in this study had a diagnosis of opioid dependence, only 21 reported the use of opiates at the initial visit.”
Quote in the paperNot a substantial claim - Findingown data
Treatment retention at six months did not differ significantly between the methadone and buprenorphine/naloxone groups.
“Twenty-six (48.2%) participants completed the treatment at 6 months, 13 in each treatment condition. Therefore, treatment retention did not significantly differ between the two treatments.”
Quote in the paperSubstantial claim - Findingown data
The methadone and buprenorphine/naloxone groups did not differ significantly in percent change in functioning from baseline at six months.
“There were no significant differences. No significant differences were found in percent change in functioning from baseline (Table 3).”
Quote in the paperNot a substantial claim - Findingown data
In patients with chronic pain and co-existent opioid addiction, six months of continuous treatment with either buprenorphine/naloxone or methadone produced analgesia.
“Both 6-month continuous buprenorphine/naloxone and methadone treatment resulted in analgesia.”
Quote in the paperSubstantial claim
- Findingown data
Among participants who tested positive for cocaine at baseline, none completed the study on the assigned medication, whereas 21 of 46 who tested negative did so (P = 0.034).
“Of the 7 participants who tested positive for cocaine at baseline, none (0%) completed the study on the study medication, while of the 46 participants who tested negative for cocaine, 21 (45.7%) completed the study on the study medication (P = 0.034).”
Quote in the paperNot a substantial claim - Findingown data
Completion of the study on the assigned medication was associated with not being covered by Medicaid (P = 0.025).
“Completion of the study on the study medication was associated with younger age (P = 0.038), not being covered by Medicaid (P = 0.025), younger age of onset of opioid use (P = 0.016), and younger age of onset of an opioid problem (P = 0.032).”
Quote in the paperNot a substantial claim - Findingown data
Completion of the study on the assigned medication was associated with younger age of onset of an opioid problem (P = 0.032).
“Completion of the study on the study medication was associated with younger age (P = 0.038), not being covered by Medicaid (P = 0.025), younger age of onset of opioid use (P = 0.016), and younger age of onset of an opioid problem (P = 0.032).”
Quote in the paperNot a substantial claim - Findingreasoning
Participants reported more drug use than was detected by urine toxicology.
“We found that participants reported more drug use than we observed with urine toxicology.”
Quote in the paperNot a substantial claim - Findingown data
Completion of the study on the assigned medication was associated with younger age (P = 0.038).
“Completion of the study on the study medication was associated with younger age (P = 0.038), not being covered by Medicaid (P = 0.025), younger age of onset of opioid use (P = 0.016), and younger age of onset of an opioid problem (P = 0.032).”
Quote in the paperNot a substantial claim - Findingown data
Completion of the study on the assigned medication was associated with younger age of onset of opioid use (P = 0.016).
“Completion of the study on the study medication was associated with younger age (P = 0.038), not being covered by Medicaid (P = 0.025), younger age of onset of opioid use (P = 0.016), and younger age of onset of an opioid problem (P = 0.032).”
Quote in the paperNot a substantial claim - Findingown data
Male gender was associated with remaining on the assigned study medication (P = 0.035).
“Male gender was associated with staying on the study medication (P = 0.035).”
Quote in the paperNot a substantial claim - Findingown data
The methadone and buprenorphine/naloxone groups did not differ significantly in percent change in pain from baseline at six months.
“However, there were no significant differences between the treatment groups (Table 3).”
Quote in the paperSubstantial claim - Findingown data
Participants who did not switch study medication reported lower functioning than those who switched (P = 0.022).
“Participants who did not switch the study medication reported lower functioning than participants who switched the study medication (P = 0.022).”
Quote in the paperNot a substantial claim - Interpretationreasoning
The absence of dose escalations and of pain worsening further suggests that the studied treatments were effective.
“However, the lack of dose escalations and worsening of pain further suggests the effectiveness of the studied treatments.”
Quote in the paperSubstantial claim - Interpretationreasoning
Patients in this study were surprisingly honest about self-reported drug use because they reported more drug use than was found in urine.
“Therefore, patients in this study were surprisingly honest about the self-report of drug use because they reported to have used more drugs than was found in the urine.”
Quote in the paperNot a substantial claim - Premisecitation
Buprenorphine has a better safety profile than methadone.
“Although methadone is superior to buprenorphine in improving addiction outcomes in opioid-dependent patients, buprenorphine has a better safety profile.21–23, 25”
Quote in the paperSubstantial claim0 of 4 sources checked - Study design and conductown data
Participants randomized to methadone had a significantly higher mean baseline functioning score than those randomized to buprenorphine/naloxone (P = 0.035).
“Participants randomized to methadone reported a significantly greater mean baseline functioning score than participants randomized to buprenorphine/naloxone (P = 0.035).”
Quote in the paperNot a substantial claim - Study design and conductnone given
The pain and functioning measures used in the study (NRS) might not have been sensitive enough to assess nuances of improvement in functioning and pain.
“The measures for pain and functioning used in this study (i.e., NRS) might not have been sensitive enough to assess the nuances of improvement in functioning and pain.”
Quote in the paperSubstantial claim - Study design and conductown data
Twenty-one participants (38.9%) completed the study on their randomized study medication.
“Twenty-one (38.9%) participants completed the study on their randomized study medication.”
Quote in the paperNot a substantial claim - Interpretationown data
Both buprenorphine/naloxone and methadone treatment for six months reduce chronic non-malignant pain in patients with co-existent opioid addiction.
“We conclude that both buprenorphine/naloxone and methadone treatment for 6 months reduce chronic non-malignant pain in patients with co-existent opioid addiction.”
Quote in the paperSubstantial claim - Study design and conductown data
Baseline characteristics did not differ between participants who completed the study and those who did not.
“Because the baseline characteristics did not differ between completers and non-completers of the study only the completers were included in the analysis of analgesia, functioning, and illicit drug use (Table 1).”
Quote in the paperSubstantial claim - Study design and conductown data
Among study completers, a greater proportion of those randomized to buprenorphine/naloxone had been convicted of a crime compared with those randomized to methadone (P = 0.011).
“Among completers of the study, a greater proportion of participants randomized to buprenorphine/naloxone were convicted of a crime (P = 0.011) and had a greater number of convictions (P = 0.04) than participants randomized to methadone (Table 3).”
Quote in the paperNot a substantial claim - Study design and conductown data
Fourteen participants (25.9%) changed study medications during the study because they perceived their assigned medication as inadequate for pain or cravings or because of side effects.
“Fourteen (25.9%) participants changed study medications during the study because they perceived the effect of the medication that they were randomized to as inadequate in relieving pain or controlling cravings or due to side effects.”
Quote in the paperNot a substantial claim - Interpretationreasoning
The discrepancy between self-report and urine toxicology can be explained by the timing of drug use.
“The discrepancy between self-report and urine toxicology can be explained by the timing of drug use.”
Quote in the paperSubstantial claim - Study design and conductown data
Among study completers, those randomized to buprenorphine/naloxone had a greater number of convictions than those randomized to methadone (P = 0.04).
“Among completers of the study, a greater proportion of participants randomized to buprenorphine/naloxone were convicted of a crime (P = 0.011) and had a greater number of convictions (P = 0.04) than participants randomized to methadone (Table 3).”
Quote in the paperNot a substantial claim - Study design and conductreasoning
The small sample size limited the ability to identify subgroups of patients who might do well with non-opioid pain management.
“The small sample size limited our ability to identify sub-groups of patients (e.g., those with no prior treatment for substance abuse or with no prior arrests) who might do well with non-opioid pain management.”
Quote in the paperNot a substantial claim - Study design and conductnone given
The participants represented a heterogeneous group regarding their pain condition and the imaging evidence for a pain condition.
“The participants of this study represented a heterogeneous group regarding their pain condition and the imaging evidence for a pain condition.”
Quote in the paperNot a substantial claim - Interpretationcitation
The finding that treatment retention did not differ between methadone and buprenorphine is consistent with a study by Mattick and associates, which showed no difference in retention between these medications in opioid-dependent patients.
“This is consistent with a study by Mattick and associates, which showed that treatment retention did not differ between methadone and buprenorphine treatment in opioid-dependent patients.25”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Mattick and associates
Not checked in the free run.
- cites [25] Mattick R P, 2008, Cochrane Database of Systematic Rev
Not checked in the free run.
- Study design and conductown data
Twenty-six participants (48.1%) completed the study.
“Twenty-six (48.1%) participants completed the study.”
Quote in the paperNot a substantial claim - Premisecitation
Methadone is superior to buprenorphine in improving addiction outcomes in opioid-dependent patients.
“Although methadone is superior to buprenorphine in improving addiction outcomes in opioid-dependent patients, buprenorphine has a better safety profile.21–23, 25”
Quote in the paperSubstantial claim0 of 4 sources checked - Premisecitation
The buprenorphine dose range used in the study came from a study by Malinoff and associates showing that these doses were effective in relieving chronic pain.
“The dose range of buprenorphine originated from a study by Malinoff and associates showing that these doses of buprenorphine were effective in relieving chronic pain.31”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] source
Not checked in the free run.
- Interpretationreasoning
The baseline difference in functioning did not affect the treatment results at the six-month follow-up.
“suggesting that the baseline difference in functioning did not affect the treatment results at the 6 months follow-up.”
Quote in the paperNot a substantial claim
- May combine two claims. 11
- Classified as probably not a substantial claim. 8
May combine two claims.
Findingown dataAlcohol use, cocaine use, and other illicit drug use did not differ between the two treatment conditions in this study.
“In the present study, alcohol use, cocaine use, and other illicit drug use did not differ between the two treatment conditions.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAt six months, five participants in the buprenorphine/naloxone group reported opioid use, whereas none in the methadone group did, and this difference was statistically significant (P = 0.039).
“At 6 months, 5 participants in the buprenorphine/naloxone group reported the use of opioids compared to none of the participants in the methadone group (Table 3); this difference was statistically significant (P = 0.039).”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductown dataParticipants were randomized into two groups using a pre-determined 3:3 ratio block randomization procedure by drawing lots.
“After informed consent was obtained, participants were randomized into one of two groups that were pre-determined by drawing lots using a 3:3 ratio, block randomization procedure.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductreasoningThe study was not double-blind and not double-dummy.
“This is a preliminary study with a small convenience sample of treatment-seeking individuals and high drop-out rate that was not a double-blind and double-dummy study.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductnone givenThe study was an open-label trial without a placebo and without a control group.
“This was an open-label trial without a placebo and a control group.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe trial was open-label.
“In this open-label trial, the remaining 54 participants with chronic pain and opioid addiction were randomly assigned to one of two 6-month treatment protocols”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThe study was a preliminary study with a small convenience sample of treatment-seeking individuals and a high drop-out rate.
“This is a preliminary study with a small convenience sample of treatment-seeking individuals and high drop-out rate that was not a double-blind and double-dummy study.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe study was registered with ClinicalTrials.gov under identifier NCT00879996.
“It was registered with the Food and Drug Administration (www.ClinicalTrials.gov) and was given the identifier number NCT00879996.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationMethadone is a long-acting μ-opioid receptor agonist and an NMDA-receptor antagonist with a half-life of 27 ± 12 hours that is effective in treating pain and opioid addiction.
“Methadone is a long-acting μ-opioid receptor agonist and an NMDA-receptor antagonist with a half-life of 27 ± 12 hours that is effective in treating pain and opioid addiction.15–17”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [15] source
Not checked in the free run.
- cites [16] Resine , T and Pasternak , G . 2001. “Opioid analgesics and antagonists”. Edited by: Hardman , J G , Limbird , L E and Gilman , A G . 521–55. New York, NY: McGraw-Hill. The pharmacological basis of therapeutics. 10th ed.
Not checked in the free run.
- cites [17] source
Not checked in the free run.
May combine two claims.
PremisecitationBuprenorphine is a partial μ-opioid receptor agonist and κ-opioid receptor antagonist with a half-life of 2.33 ± 0.24 hours that might be an alternative to methadone because it is effective in treating opioid addiction or pain.
“Buprenorphine, a partial μ-opioid receptor agonist and κ-opioid receptor antagonist with a half-life of 2.33 ± 0.24 hours might be an alternative to methadone because it is effective in treating opioid addiction or pain.21–26”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [21] source
Not checked in the free run.
- cites [22] source
Not checked in the free run.
- cites [23] source
Not checked in the free run.
- cites [24] source
Not checked in the free run.
- cites [25] Mattick R P, 2008, Cochrane Database of Systematic Rev
Not checked in the free run.
- cites [26] source
Not checked in the free run.
May combine two claims.
Study design and conductown dataThe treatment arms did not statistically differ at baseline in demographics, drug-taking history, treatment history, criminal history, self-reported alcohol, opiate, and other drug use, positive urine for cocaine, opiates, and other drugs, and pain.
“The treatment arms did not statistically differ in participants’ demographics, drug-taking history, treatment history, criminal history, self-reported alcohol, opiate, and other drug use, positive urine for cocaine, opiates, and other drugs, and pain.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe methadone dose range was chosen according to a recommendation by Hardman and associates that the typical initial oral dose of methadone for pain is 2.5 to 15 mg, depending on pain severity.
“The dose range of methadone was chosen according to the recommendation by Hardman and associates stating that the typical initial oral dose of methadone for pain is 2.5 to 15 mg, depending on the severity of pain.16”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] Resine , T and Pasternak , G . 2001. “Opioid analgesics and antagonists”. Edited by: Hardman , J G , Limbird , L E and Gilman , A G . 521–55. New York, NY: McGraw-Hill. The pharmacological basis of therapeutics. 10th ed.
Not checked in the free run.
May combine two claims.
PremisecitationLong-acting opioids may offer pain control with a decreased risk for medication misuse.
“Long-acting opioids may offer pain control with a decreased risk for medication misuse.14”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [14] Savage S R, 2003
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductcitationA diagnosis of opioid dependence was confirmed using the DAST score (>4) and a 7-item checklist based on DSM-IV-TR criteria for opioid dependence.
“A diagnosis of opioid dependence was confirmed using the DAST score (> 4) and a 7-item checklist based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) for “opioid dependence.”30”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [30] American Psychiatric Association, 2000
Not checked in the free run.
May combine two claims.
PremisecitationA case study of four chronic pain patients with co-existent opioid addiction who received methadone found that three stayed in treatment for 19-21 months and stopped intravenous use.
“A case study of 4 chronic pain patients with co-existent opioid addiction who received methadone treatment found that 3 stayed in treatment for 19–21 months and stopped intravenous use.29”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] Kennedy J A, 1990, JSAT
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationTreatment with steady doses of buprenorphine/naloxone for six months results in treatment retention superior to detoxification followed by abstinence in chronic pain patients with co-existent opioid addiction.
“According to Blondell and his associates, treatment with steady doses of buprenorphine/naloxone for 6 months results in treatment retention superior to detoxification followed by abstinence in chronic pain patients with a co-existent opioid addiction.13”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] source
Not checked in the free run.
May combine two claims.
PremisecitationBuprenorphine's ceiling on agonist activity limits its abuse liability and reduces the probability of respiratory depression and overdose death, giving it a safety profile superior to methadone.
“Buprenorphine’s ceiling on its agonist activity limits its abuse liability and reduces the probability of respiratory depression and overdose death, resulting in a safety profile superior to methadone.27”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] Walsh S L, 1995, J Pharmacol Expl Ther source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMethadone or propoxyphene treatment produced better treatment retention than detoxification followed by psychotherapy in patients with chronic pain and co-existent addiction.
“Similarly, Tennant and Rawson showed that methadone or propoxyphene treatment produced better treatment retention than detoxification followed by psychotherapy in patients with chronic pain and co-existent addiction.28”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn that case study, pain measured by the visual analogue scale did not significantly decrease.
“Pain as measured by the visual analogue scale did not significantly decrease.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] Kennedy J A, 1990, JSAT
Not checked in the free run.
The paper relies on this without support.
Randomized clinical trials have not compared methadone and buprenorphine in patients with chronic pain and co-existent opioid addiction.
“Randomized clinical trials have not compared methadone and buprenorphine in patients with chronic pain and co-existent opioid addiction.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Of the remaining 4 SUD trials with a medium-term follow-up, a small-to-medium effect on pain reduction from baseline to medium-term follow-up was reported in all.
“Of the remaining 4 trials with a medium-term followup, 30,39,40,45 although a small-to-medium effect on pain reduction from baseline to medium-term follow-up was reported in all, with 1 reporting a large ES, 30 one trial found this effect was only significant among women participants. 40”
From The Effectiveness of Interventions for Improving Chronic Pain Symptoms Among People With Mental Illness: A Systematic Review (2024) · cites this paper as [45]
Five trials implemented pharmacological-based intervention.
“Five trials in total implemented pharmacologicalbased intervention, 41-45”
From The Effectiveness of Interventions for Improving Chronic Pain Symptoms Among People With Mental Illness: A Systematic Review (2024) · cites this paper as [45]
Of all 3 trials recording adverse events, no severe adverse events were reported related to the intervention.
“Of the all 3 trials recording AEs, 35,36,45 no severe AEs were reported related to the intervention.”
From The Effectiveness of Interventions for Improving Chronic Pain Symptoms Among People With Mental Illness: A Systematic Review (2024) · cites this paper as [45]
The Results (Completion of Study and Treatment; page unavailable) mention that some participants changed medications partly because of side effects. The Methods list the measured outcomes, but neither those passages nor searches for severe or serious adverse events establish whether intervention-related severe adverse events were recorded or absent in this trial. (LLM, conf=0.72)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Different percentages reported for the same completion count
MinorThe paper gives the same numerator and denominator for study completion but reports two slightly different percentages. One place says 26 participants were 48.1% of the sample, while another says 26 participants were 48.2%.
“Twenty-six (48.1%) participants completed the study.”
“Twenty-six (48.2%) participants completed the treatment at 6 months, 13 in each treatment condition.”
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Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence
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CDC Clinical Practice Guideline for Prescribing Opioids for Pain <b>—</b> United States, 2022
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Medication-Assisted Treatment of Opioid Use Disorder
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“In this example, low-dose buprenorphine/naloxone maintenance in a divided-dosing regimen could potentially enable pain treatment and circumvent opioid misuse; indeed, studies of OUDwith physiological dependence show buprenorphine/ naloxone to provide a benefit in mild-to-moderate pain syndromes.(25,115) Note, however,…”
BackgroundRetention in medication-assisted treatment for opiate dependence: A systematic review
Timko, C., Schultz, N. R., Cucciare, M. A., Vittorio, L. N., & Garrison‐Diehn, C. (2015) · Journal of Addictive Diseases · doi:10.1080/10550887.2016.1100960 · Cited by 487 · see citing works
“Six-month MAT retention rates were also comparable (48%) for patients with chronic non-malignant pain who received either methadone or buprenorphine/naloxone.(37) High 12-month retention rates (88%) were found among treatment-refractory patients treated with either diacetylmorphine (the active ingredient of heroin) or…”
BackgroundOpioid agonist treatment for pharmaceutical opioid dependent people
Nielsen, S., Larance, B., Degenhardt, L. J., Gowing, L., Kehler, C., & Lintzeris, N. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011117.pub2 · Cited by 247 · see citing works
Tapering Long-term Opioid Therapy in Chronic Noncancer Pain
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“Finally, as others have also noted, we found that treating pain with co-occurring substance use remains a challenge both for patients and clinicians (Neumann et al., 2013; Weiss et al., 2014).”
BackgroundCost-effectiveness of Treatments for Opioid Use Disorder
Fairley, M., Humphreys, K. N., Joyce, V. R., Bounthavong, M., Trafton, J. A., Combs, A., Oliva, E. M., Goldhaber‐Fiebert, J. D., Asch, S. M., Brandeau, M. L., et al. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2021.0247 · Cited by 163 · see citing works
Medication-Assisted Treatment for Opioid-Use Disorder
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Buprenorphine–Naloxone Therapy in Pain Management
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The Conundrum of Opioid Tapering in Long-Term Opioid Therapy for Chronic Pain: A Commentary
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Chronic pain, craving, and illicit opioid use among patients receiving opioid agonist therapy
Tsui, J. I., Lira, M. C., Cheng, D. M., Winter, M. R., Alford, D. P., Liebschutz, J. M., Edwards, R. R., & Samet, J. H. (2016) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2016.06.024 · Cited by 97 · see citing works
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Severity and Interference of Chronic Pain in Methadone-Maintained Outpatients
Dunn, K. E., Brooner, R. K., & Clark, M. R. (2014) · Pain Medicine · doi:10.1111/pme.12430 · Cited by 76 · see citing works
Griffin, M. L., McDermott, K. A., McHugh, R. K., Fitzmaurice, G. M., Jamison, R. N., & Weiss, R. D. (2016) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2016.04.023 · Cited by 71 · see citing works
“In addition, variability in the experience of pain may be the result of variation in analgesic response to opioid agonist therapy, which has been efficacious in reducing pain overall among patients with opioid dependence (Neumann et al., 2013).”
BackgroundChou, R., Weimer, M. B., & Dana, T. (2014) · Journal of Pain · doi:10.1016/j.jpain.2014.01.495 · Cited by 75 · see citing works
Aiyer, R., Gulati, A., Güngör, S., Bhatia, A., & Mehta, N. D. (2017) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000002718 · Cited by 66 · see citing works
Methadone in Pain Management: A Systematic Review
Hanna, V., & Senderovich, H. (2020) · Journal of Pain · doi:10.1016/j.jpain.2020.04.004 · Cited by 66 · see citing works
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Lim, J., Farhat, I., Douros, A., & Panagiotoglou, D. (2022) · PLoS ONE · doi:10.1371/journal.pone.0266142 · Cited by 56 · see citing works
“…Iran Parallel DB 12 w Opioid dependence NTX 28.6 NI BNX Neri 2005 Psychopharmacology Italy Parallel DB 12 m Opioid addiction BUP 25 88.71% MET Neumann 2013 Journal of Addictive Diseases USA Factorial OL 6 m Opioid dependence BNX 38.3 53.70% MET Neumann 2020 Journal of Addictive Diseases USA…”
BackgroundInfluentialPain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.
Worley, M. J., Heinzerling, K. G., SHOPTAW, S. J., & Ling, W. W. (2015) · Experimental and Clinical Psychopharmacology · doi:10.1037/pha0000039 · Cited by 49 · see citing works
“, 2013), with one randomized trial finding similar reductions in pain from BUP-NLX and low-dose methadone (Neumann et al., 2013).”
BackgroundResultInfluentialOpioid agonist treatment for people who are dependent on pharmaceutical opioids
Nielsen, S., Tse, W. C., & Larance, B. (2022) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011117.pub3 · Cited by 50 · see citing works
Endogenous opiates and behavior: 2013
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Chronic Pain and DepressionAmong Primary Care Patients Treated with Buprenorphine
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Prescribing smoked cannabis for chronic noncancer pain: preliminary recommendations.
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Is Buprenorphine Effective for Chronic Pain? A Systematic Review and Meta-analysis
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“Although these findings are mostly based on preclinical studies, a randomized trial that was included in our review reports similar reductions in pain from buprenorphine-naloxone and low-dose methadone [28].”
BackgroundHochheimer, M., & Unick, G. J. (2021) · Addictive Behaviors · doi:10.1016/j.addbeh.2021.107113 · Cited by 40 · see citing works
Primary care patient characteristics associated with completion of 6-month buprenorphine treatment
Neumann, A. M., Blondell, R. D., Azadfard, M., Nathan, G., & Homish, G. G. (2013) · Addictive Behaviors · doi:10.1016/j.addbeh.2013.07.007 · Cited by 37 · see citing works
“In addition to its success in the treatment of opioid addiction, 6-month buprenorphine treatment reduced pain in patients with chronic pain and opioid addiction (Neumann et al., 2013; Pade, Cardon, Hoffman, & Geppert, 2012).”
BackgroundSelf-citationMessina, B. G., & Worley, M. J. (2019) · Journal of Consulting and Clinical Psychology · doi:10.1037/ccp0000399 · Cited by 32 · see citing works
“Buprenorphine-naloxone (BUP-NLX) is one recommended pharmacotherapy with empirical support for reducing opioid use and achieving adequate pain control for individuals with chronic pain who are diagnosed with an opioid use disorder (Neumann et al., 2013; Weiss et al., 2011, 2015).”
BackgroundWorley, M. J., Heinzerling, K. G., SHOPTAW, S. J., & Ling, W. W. (2017) · Addiction · doi:10.1111/add.13782 · Cited by 31 · see citing works
Marie, B. S. (2014) · Pain Medicine · doi:10.1111/pme.12493 · Cited by 33 · see citing works
The role of neurologists in tackling the opioid epidemic
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Opioid use disorder in primary care: PEER umbrella systematic review of systematic reviews.
Korownyk, C. S., Perry, D., Ton, J., Kolber, M. R., Garrison, S., Thomas, B., Allan, G. M., Dugré, N., Finley, C. R., Ting, R., et al. (2019) · Europe PMC (PubMed Central) · Cited by 29 · see citing works
Buprenorphine in the treatment of opioid addiction: opportunities, challenges and strategies
Li, X., Shorter, D. I., & Kosten, T. R. (2014) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2014.955469 · Cited by 30 · see citing works
“Similarly, patients with chronic pain and comorbid opioid use disorder can be treated with buprenorphine/naloxone [28].”
BackgroundTop Ten Tips Palliative Care Clinicians Should Know About Buprenorphine
Neale, K., Weimer, M. B., Davis, M. P., Jones, K. F., Kullgren, J. G., Kale, S. S., Childers, J. W., Broglio, K., Merlin, J. S., Peck, S., et al. (2022) · Journal of Palliative Medicine · doi:10.1089/jpm.2022.0399 · Cited by 30 · see citing works
“43,44 Buprenorphine pharmacokinetics are unchanged in older adults.”
Sandhu, R., Zivanovic, R., Klaire, S. S., et al. (2019) · Canadian Journal of Pain · doi:10.1080/24740527.2019.1599279 · Cited by 28 · see citing works
“methadone for treatment of chronic pain in patients with opioid use disorder and found a significant reduction in pain in both groups.(21) An earlier review of sublingual buprenorphine as an analgesic in chronic pain concluded, based on ten studies that were mostly observational in nature, that there was a plausible r…”
Ensuring Patient Protections When Tapering Opioids: Consensus Panel Recommendations
Covington, E. C., Argoff, C. E., Ballantyne, J. C., Cowan, P., Gazelka, H. M., Hooten, W. M., Kertesz, S. G., Manhapra, A., Murphy, J. L., Stanos, S. P., et al. (2020) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2020.04.025 · Cited by 27 · see citing works
Neumann, A. M., Blondell, R. D., Hoopsick, R. A., & Homish, G. G. (2019) · Journal of Addictive Diseases · doi:10.1080/10550887.2019.1690929 · Cited by 26 · see citing works
“The inclusion criteria included: (1) medically stable [Clinical Opiate Withdrawal Scale (COWS) score 5, no acute opioid withdrawal], (2) ability to give consent, (3) ability to understand spoken and basic written English, (4) age 18-64 years, inclusive, (5) residence in one of two local counties, (6) presence of a med…”
BackgroundSelf-citationEmpirical Studies Addressing the Opioid Epidemic: An Urgent Call for Research
Stuart, G. L., Shorey, R. C., France, C. R., Macfie, J., Bell, K. M., Fortner, K. B., Towers, C. V., Schkolnik, P., & Ramsey, S. E. (2018) · Substance Abuse Research and Treatment · doi:10.1177/1178221818784294 · Cited by 22 · see citing works
Tolerability of Opioid Analgesia for Chronic Pain: A Network Meta-Analysis
Meng, Z., Yu, J., Acuff, M. E., Luo, C. T., Wang, S., Yu, L., & Huang, R. (2017) · Scientific Reports · doi:10.1038/s41598-017-02209-x · Cited by 21 · see citing works
Blondino, C., Gormley, M. A., Taylor, D. D. H., Lowery, E. P., Clifford, J. S., Burkart, B., Graves, W. C., Lü, J., & Prom‐Wormley, E. C. (2020) · Epidemiologic Reviews · doi:10.1093/epirev/mxaa005 · Cited by 19 · see citing works
Ma, R., Romano, E., Ashworth, M., Smith, T. O., Vancampfort, D., Scott, W., Gaughran, F., Stewart, R., & Stubbs, B. (2024) · The Journal of Pain · doi:10.1016/j.jpain.2023.11.004 · Cited by 19 · see citing works
Shulman, M., Luo, S. X., Campbell, A. N. C., Scodes, J. M., Pavlicová, M., Broffman, A., Saxon, A. J., & Nunes, E. V. (2020) · Journal of Addiction Medicine · doi:10.1097/adm.0000000000000630 · Cited by 17 · see citing works
Samaan, Z. (2016) · Pain Physician · doi:10.36076/ppj/2016.19.e181 · Cited by 17 · see citing works
An observational study of buprenorphine treatment of the prescription opioid dependent pain patient
Streltzer, J., Davidson, R., & Goebert, D. A. (2015) · American Journal on Addictions · doi:10.1111/ajad.12198 · Cited by 16 · see citing works
Manhapra, A., MacLean, R. R., Rosenheck, R. A., & Becker, W. C. (2023) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15972 · Cited by 17 · see citing works
“77,78 If buprenorphine is not a viable choice, other long-acting formulations of short-acting opioids, such as sustained release morphine or oxycodone, may also be used as less optimal treatment options.”
Cost-effectiveness of office-based buprenorphine treatment for opioid use disorder
Qian, G. L., Rao, I. J., Humphreys, K. N., Owens, D. K., & Brandeau, M. L. (2022) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2022.109762 · Cited by 15 · see citing works
Chronic Pain, Opioid Use Disorder, and Clinical Management Among Older Adults
Potru, S., & Tang, Y. (2021) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.20210002 · Cited by 16 · see citing works
Managing Chronic Pain in Patients With Opioid Dependence
Liebschutz, J. M., Beers, D., & Lange, A. V. (2014) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-014-0015-4 · Cited by 15 · see citing works
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Kappa Opioid Signaling at the Crossroads of Chronic Pain and Opioid Addiction
Cahill, C. M., Lueptow, L. M., Kim, H., Shusharla, R., Bishop, A., & Evans, C. J. (2021) · Handbook of experimental pharmacology · doi:10.1007/164_2021_434 · Cited by 12 · see citing works
Bednasz, C. J., Luque, A. E., Zingman, B. S., Fischl, M. A., Gripshover, B., Venuto, C. S., Gu, J., Feng, Z., DiFrancesco, R., Morse, G. D., et al. (2016) · Current Vascular Pharmacology · doi:10.2174/1570161114666160106151652 · Cited by 12 · see citing works
Nack, B., Haas, S. E., & Portnof, J. E. (2017) · Anesthesia Progress · doi:10.2344/anpr-64-03-09 · Cited by 11 · see citing works
Hayes, B. T., Li, P., Nienaltow, T., Torres‐Lockhart, K., Khalid, L., & Fox, A. D. (2023) · Journal of Substance Use and Addiction Treatment · doi:10.1016/j.josat.2023.209261 · Cited by 11 · see citing works
Aquino, J. P. D., Flores, J. M., Avila-Quintero, V. J., Compton, P. A., & Sofuoglu, M. (2020) · Addiction Biology · doi:10.1111/adb.12964 · Cited by 10 · see citing works
“Four studies investigating the analgesic effects of traditional MOUD found no difference in experimental or spontaneous pain with methadone, buprenorphine, or IM XR naltrexone.(23,26,31,32) Overall, the assembly of information from these studies provides a conflicting picture with regards to the important question of…”
Backgroundystematic review on the clinical management of chronic pain and comorbid opioid use disorder
Jiménez-Fernández, B., Calomarde-Gómez, C., López-Lazcano, A., Lligoña, A., Gual, A., & López‐Pelayo, H. (2022) · Adicciones · doi:10.20882/adicciones.1680 · Cited by 8 · see citing works
Archambault, L., Bertrand, K., Martel, M. O., Berube, M., Belhouari, S., & Perreault, M. (2024) · Journal of Clinical Nursing · doi:10.1111/jocn.17139 · Cited by 14 · see citing works
Ellerbroek, H., van den Heuvel, S. A. S., Dahan, A., Timmerman, H., Kramers, C., & Schellekens, A. (2022) · Addiction Science & Clinical Practice · doi:10.1186/s13722-022-00326-1 · Cited by 8 · see citing works
“Two small studies by Neumann et al. have compared effectiveness of methadone and BuNa in patients with chronic pain and prescription OUD, but remain inconclusive.”
BackgroundResultInfluentialPharmacological Strategies to Decrease Long-Term Prescription Opioid Use: A Systematic Review
Ellerbroek, H., Kalkman, G. A., Kramers, C., Schellekens, A., & van den Bemt, B. J. F. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13247770 · Cited by 6 · see citing works
Assessment of Co-Occurring Substance Use During Opiate Treatment Programs in the United States
Gormley, M. A., Blondino, C., Taylor, D. D. H., Lowery, E. P., Clifford, J. S., Burkart, B., Graves, W. C., Prom‐Wormley, E. C., & Lü, J. (2020) · Epidemiologic Reviews · doi:10.1093/epirev/mxaa009 · Cited by 6 · see citing works
Janssen, É., Vuolo, M., Spilka, S., & Airagnes, G. (2024) · Harm Reduction Journal · doi:10.1186/s12954-024-00934-x · Cited by 5 · see citing works
“…yields inconclusive results: while studies argue the superiority of methadone in improving misuse outcomes in opioid patients (decreased risk of relapse, improvement of psychological status [7]), buprenorphine reduces risk of overdose and is more easily manageable on a daily basis [8].”
ResultZhaleh, H., Mahdizadeh, H., & khoshkhoi, S. (2023) · Asian Pacific Journal of Cancer Prevention · doi:10.31557/apjcp.2023.24.3.801 · Cited by 5 · see citing works
“Methadone is used in treating chronic pain due to its activity in N-methyl-D-aspartate (NMDR) and μ opioid receptors and seems to be more effective in neuropathic pains (Leppert, 2009; Neumann et al., 2013).”
BackgroundWang, A., Shulman, M., Choo, T.-H. J., Pavlicová, M., Langleben, D. D., Nunes, E. V., & Rotrosen, J. (2021) · Addiction Biology · doi:10.1111/adb.13112 · Cited by 5 · see citing works
“6-month randomized controlled study found that BUP-NX and methadone had similar analgesic effects on OUD patients with chronic pain.(14) Similarly, our group previously found no difference”
BackgroundSublingual Buprenorphine/Naloxone and Multi-Modal Management for High-Risk Chronic Pain Patients
Kaski, S. W., Marshalek, P. J., Herschler, J., Wen, S., & Zheng, W. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10050973 · Cited by 5 · see citing works
Methadone and Buprenorphine: The Place of Opiate Replacement Therapies
Buchholz, J. R., & Saxon, A. J. (2016) · Springer eBooks · doi:10.1007/978-3-319-29863-4_6 · Cited by 5 · see citing works
Modeling Health and Economic Outcomes of Providing Stable Housing to Homeless Adults With OUD
Rao, I. J., & Brandeau, M. L. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.17103 · Cited by 4 · see citing works
Qian, G. L., Humphreys, K. N., Goldhaber‐Fiebert, J. D., & Brandeau, M. L. (2024) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2024.111112 · Cited by 4 · see citing works
Montalvo, C., Genovese, N., & Renner, J. A. (2019) · Substance Abuse · doi:10.1080/08897077.2019.1572050 · Cited by 4 · see citing works
“to dosing despite clinically some providers prescribing it 3 times a day (TID).(1,2) Additionally, patients undergoing opi-”
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Systematic evidence review on methadone harms and comparative harms
Chou, R., Weimer, M. B., & Fiellin, D. A. (2014) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2014.02.113 · Cited by 3 · see citing works
Kaya-Akyüzlü, D., Özkan-Kotiloğlu, S., Danışman, M., & Bal, C. (2024) · Neuroscience Letters · doi:10.1016/j.neulet.2024.137846 · Cited by 2 · see citing works
Wei, Y. J., Winterstein, A. G., Fillingim, R. B., Schmidt, S., & Schmidt, S. O. (2026) · PLoS Medicine · doi:10.1371/journal.pmed.1004846 · Cited by 1 · see citing works
“Although studies have examined pain outcomes among patients prescribed medications for OUD, their quality of evidence is low, with small sample sizes, and they are mostly restricted to patients in inpatient or peri-and post-operative settings [10, 20-22].”
InfluentialYou, D. S., Edwards, K. A., Ziadni, M. S., Kim, S., Klein, M. R., Cox, R., Raney, E., Kuchera, J., & Darnall, B. D. (2025) · doi:10.2196/preprints.86070 · Cited by 1 · see citing works
Shanbhag, D. (2020) · Clinical Research in Practice The Journal of Team Hippocrates · doi:10.22237/crp/1593562740 · Cited by 1 · see citing works
“Additionally, the study focused exclusively on patients with existing chronic pain, which is not applicable to this clinical context.(3)”
BackgroundBarrio, P., Ezzeldin, M. Y., Bruguera, P., Pérez, A. I. M., Mansilla, S., Fàbrega, M. G. I., Lligoña, A., Mondón, S., & Balcells‐Oliveró, M. (2016) · Adicciones · doi:10.20882/adicciones.832 · Cited by 2 · see citing works
Investigative Analysis of Inappropriate Opioid Use for Cancer Outpatient
Shimizu, K., Ikenaga, M., Sugita, T., Takeohara, M., Kazuno, C., Kubota, T., Okoshi, T., Aoki, S., Kamura, R., & Imamura, T. (2016) · Palliative Care Research · doi:10.2512/jspm.11.174 · Cited by 1 · see citing works
Review article. Buprenorphine in the workers' compensation setting
Colameco, S., & Pohl, M. (2014) · Journal of Opioid Management · doi:10.5055/jom.2014.0215 · Cited by 1 · see citing works
Health and Economic Impacts of Stable Housing Provision for Older Adults
Gande, V., Goldhaber‐Fiebert, J. D., & Brandeau, M. L. (2026) · JAMA Health Forum · doi:10.1001/jamahealthforum.2026.0624 · Cited by 1 · see citing works
You, D. S., Edwards, K. A., Ziadni, M. S., Kim, S., Klein, M. R., Cox, R., Raney, E., Kuchera, J., & Darnall, B. D. (2026) · JMIR Formative Research · doi:10.2196/86070
“However, long-term opioid therapy provides only modest pain relief [3-5] and is often accompanied by adverse side effects [6,7].”
Caring Through Complexity: Developing a Palliative Care Opioid and Stimulant Use Disorder Workflow
Dussault, N. E., Ma, J., Ivey, N., et al. (2025) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2025.12.017
Frohe, T. M., Janssen, T., Garner, B. R., & Becker, S. J. (2024) · BMC Public Health · doi:10.1186/s12889-024-20077-9
“Patients were enrolled into Project [Masked] shortly after their induction on MOUD, and even though pain is associated with worse MOUD outcomes [55], the receipt of MOUD with methadone or buprenorphine has been shown to effectively reduce pain [56, 57].”
MethodBuchholz, J. R., Kalmoe, M. C., Stamschror, J. D., & Saxon, A. J. (2023) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780197618431.013.18
Frohe, T. M., Janssen, T., Garner, B. R., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3158420/v1
Methadone Contrasted with Acetaminophen Codeine Plus Clonidine: An Inpatient Pilot Study
Shafti, S. S. (2021) · Current Psychopharmacologye · doi:10.2174/2211556010666210823121451
Patient in Rehab and on Buprenorphine/Methadone/Naltrexone/Naloxone
Wendahl, A. J., & Pride, K. (2020) · Springer eBooks · doi:10.1007/978-3-030-40449-9_14
Duncan, J., & Stephens, L. (2019) · Evidence-Based Practice · doi:10.1097/ebp.0000000000000268
Responding to illicit drug use in family practice
Robertson, J. R., & Robertson, A. R. (2015) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000174
“The need to better understand the use and efficacy of methadone and buprenorphine as analgesics [43] is critical, as is an understanding of routes into chronic opioid prescribing [44].”
BackgroundPrescrire du cannabis fumé pour la douleur chronique non cancéreuse: Recommandations préliminaires
Kahan, M., Srivastava, A., Spithoff, S. M., & Bromley, L. A. (2014) · Europe PMC (PubMed Central)
- Authors
- Neumann, A. M., Blondell, R. D., Jaanimägi, U., Giambrone, A. K., Homish, G. G., Lozano, J. R., Kowalik, U., & Azadfard, M.
- Affiliations
- University at Buffalo, State University of New York (US)
- Venue
- Journal of Addictive Diseases
- Publisher
- Informa UK Limited
- Published
- 2013-01-01
- Volume
- 32
- Issue
- 1
- Pages
- 68-78
- ISSN
- 1055-0887 (ISSN-L)
- 1545-0848
- PMC
- PMC3604999
- OpenAlex
- W1968420582
- Semantic Scholar
- 6ecb8e730278d7e307199a404c63fdce401d8479
- Cited by
- 90
- References
- 34
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 3 · 2017: 5 · 2016: 10 · 2015: 9 · 2014: 12 · 2013: 1
- FWCI
- 10.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Addictive Diseases (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R03DA029768)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- methadone, buprenorphine/naloxone, opioid use disorder, chronic pain, prescription opioids, analgesia, illicit opioid use, opioid use disorder treatment
- MeSH terms
- Administration, Sublingual, Analgesics, Opioid, Analysis of Variance, Buprenorphine, Drug Combinations, Female, Humans, Male, Methadone, Middle Aged, Naloxone, Opioid-Related Disorders, Severity of Illness Index, Substance Abuse Detection, Treatment Outcome, Chronic Pain, Prescription Drug Misuse
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