Withdrawal From Methadone Maintenance: Rate of Withdrawal and Expectation
Abstract
One hundred twenty-seven successfully methadone-hydrochloride-maintained patients were randomly assigned to one of the following four groups and studied for 30 weeks: (1) known maintenance-patients were maintained on methadone under open conditions; (2) blind maintenance-patients were maintained on methadone under double blind conditions; (3) rapid withdrawal-patients were withdrawn under double-blind conditions at a rate of 10% of initial dose per week; (4) gradual withdrawal-patients were withdrawn under double-blind conditions at a rate of 3% of initial dose per week. Differences in dropout rates, illicit drug use, symptoms scores, and requests for study interruption indicate that withdrawal from methadone maintenance should be carried out at approximately 3% of initial dose per week. Better patient preparation also is indicated to reduce the effects of expectation.
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Because 47% of patients were still unable to achieve opioid cessation at a reduction rate of 3%/week, an even slower reduction schedule might improve cessation rates further.
“As 47% of patients were still unable to achieve opioid cessation at a reduction rate of 3%/week, it may be that an even slower reduction schedule might improve cessation rates further. 35”
From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [35]
Deviation from the protocol did not occur at high doses (greater than 2 mg/day of methadone) but started to occur when doses approached 2 mg/day of methadone, with most patients refusing a linear rate of reduction completely at 1.5 mg/day of methadone.
“Deviation from the protocol did not occur at high doses (greater than 2 mg/day of methadone) but started to occur when doses approached 2 mg/day of methadone, with most patients refusing a linear rate of reduction completely at 1.5 mg/day of methadone. 35”
From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [35]
The hyperbolic relationship between dose and activity may explain why in studies that have employed linear tapers patients do not comply with the dose tapering regimen, and instead modify the process to more readily fit a hyperbolic pattern.
“This hyperbolic relationship between dose and activity may explain why in studies that have employed linear tapers (e.g. 10% of the original dose per week) patients do not comply with the dose tapering regimen, and instead modify the process to more readily fit a hyperbolic pattern (Figure 3). 35”
From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [35]
In an older study, patients tapered by 3% of their original dose per week had reduced dropout rates, less illicit drug use, lower withdrawal symptom scores, and fewer requests for study interruption compared with patients tapered by 10% of their original dose per week.
“This is consistent with the findings of an older study that found reduced dropout rates, less illicit drug use, lower withdrawal symptom scores and fewer requests for study interruption in patients tapered by 3% of their original dose per week (53% achieved opioid cessation) compared with 10% of their original dose per week (24% achieved opioid cessation). 35”
From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [35]
In an older study, 53% of patients tapered by 3% of their original dose per week achieved opioid cessation compared with 24% of patients tapered by 10% of their original dose per week.
“This is consistent with the findings of an older study that found reduced dropout rates, less illicit drug use, lower withdrawal symptom scores and fewer requests for study interruption in patients tapered by 3% of their original dose per week (53% achieved opioid cessation) compared with 10% of their original dose per week (24% achieved opioid cessation). 35”
From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [35]
The rapid withdrawal group ended at a higher total methadone dose for the group.
“Overall, the rapid withdrawal group ended at a higher total methadone dose for the group, a finding consistent with Aesop’s fable, ‘The Tortoise and the Hare’. 35”
From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [35]
Patients provided with maintenance treatment but blinded show drop-out rates almost as high as those gradually withdrawing from medication, suggesting expectations of withdrawal (nocebo effects) may contribute to patients' difficulties.
“Patients who are provided with maintenance treatment but blinded (so they do not know whether they are reducing or maintaining) show drop-out rates almost as high as those who are gradually withdrawing from medication, 35 suggesting that expectations of withdrawal (nocebo effects) may contribute to patients’ difficulties.”
From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [35]
Expectancy effects have been shown to play a role in tapering.
“Lastly, expectancy effects have been shown to play a role in tapering. 35”
From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [35]
Cites
Martin, W. R. (1973) · Archives of General Psychiatry · doi:10.1001/archpsyc.1973.01750320112017 · Cited by 266 · see citing works
Detoxification of Rehabilitated Methadone-Maintained Patients
Cushman, P. (1973) · JAMA · doi:10.1001/jama.1973.03230070013002 · Cited by 88 · see citing works
Detoxification of Rehabilitated Methadone Patients: Frequency and Predictors of Long-Term Success
Cushman, P. (1974) · The American Journal of Drug and Alcohol Abuse · doi:10.3109/00952997409011032 · Cited by 39 · see citing works
Kaistha, K. K., Tadrus, R., & Janda, R. (1975) · Journal of Chromatography A · doi:10.1016/0021-9673(75)80012-4 · Cited by 37 · see citing works
Abrupt Withdrawal of Maintenance Methadone
Lipkowitz, M. H. (1971) · JAMA · doi:10.1001/jama.1971.03190130062017 · Cited by 13 · see citing works
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Cited by
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Management of Drug and Alcohol Withdrawal
Kosten, T. R., & O'Connor, P. G. (2003) · New England Journal of Medicine · doi:10.1056/nejmra020617 · Cited by 563 · see citing works
Treatment of opioid-use disorders
Schuckit, M. A. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1604339 · Cited by 540 · see citing works
Nicotine withdrawal versus other drug withdrawal syndromes: similarities and dissimilarities
HUGHES, J. R., HIGGINS, S. T., & BICKEL, W. K. (1994) · Addiction · doi:10.1111/j.1360-0443.1994.tb03744.x · Cited by 312 · see citing works
Gossop, M., Marsden, J., Stewart, D., & Treacy, S. (2001) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(00)00211-8 · Cited by 175 · see citing works
Office-Based Treatment of Opioid-Dependent Patients
Fiellin, D. A., & O'Connor, P. G. (2002) · New England Journal of Medicine · doi:10.1056/nejmcp013579 · Cited by 148 · see citing works
Nosyk, B., Sun, H., Evans, E., Marsh, D. C., Anglin, M. D., Hser, Y., & Anis, A. H. (2012) · Addiction · doi:10.1111/j.1360-0443.2012.03870.x · Cited by 81 · see citing works
Dunn, K. E., Sigmon, S. C., Strain, E. C., Heil, S. H., & Higgins, S. T. (2011) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2011.05.033 · Cited by 65 · see citing works
Slow tapering from methadone maintenance in a program encouraging indefinite maintenance
Calsyn, D. A., Malcy, J. A., & Saxon, A. J. (2006) · Journal of Substance Abuse Treatment · doi:10.1016/j.jsat.2005.11.007 · Cited by 55 · see citing works
Relapse in opiate addicts: a behavioral analysis
Chaney, E. F., Roszell, D. K., & Cummings, C. (1982) · Addictive Behaviors · doi:10.1016/0306-4603(82)90058-2 · Cited by 53 · see citing works
Strang, J., & Gossop, M. (1990) · Addictive Behaviors · doi:10.1016/0306-4603(90)90054-2 · Cited by 42 · see citing works
Tapering opioids: a comprehensive qualitative review
Davis, M. P., Digwood, G., Mehta, Z., & McPherson, M. L. (2020) · Annals of Palliative Medicine · doi:10.21037/apm.2019.12.10 · Cited by 33 · see citing works
Stratégies d’arrêt du traitement de substitution par méthadone
Ksouda, K., Bloch, V., Dugarin, J., Dupuy, G., Laqueille, X., Lépine, J.-P., & Vorspan, F. (2013) · La Presse Médicale · doi:10.1016/j.lpm.2012.04.011 · Cited by 13 · see citing works
Lu, Q., Zou, X., Liu, Y., Gong, C., & Ling, L. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16152800 · Cited by 13 · see citing works
Abie Horowitz, M., Framer, A., Strang, J., & Taylor, D. (2025) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253251371504
“35 Patients who are provided with maintenance treatment but blinded (so they do not know whether they are reducing or maintaining) show drop-out rates almost as high as those who are gradually withdrawing from medication, 35 suggesting that expectations of withdrawal (nocebo effects) may contribute…”
Influential
- Authors
- Senay, E. C.
- Corresponding author
- Senay, Edward C.
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 1977-03-01
- Volume
- 34
- Issue
- 3
- Pages
- 361
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W1989126239
- Cited by
- 117
- References
- 5
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 1 · 2013: 1 · 2012: 2
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Keywords
- methadone maintenance treatment, opioid use disorder, opioid withdrawal, dropout rates, illicit drug use, withdrawal symptoms, patient preparation, expectancy effects
- MeSH terms
- Adult, Drug Administration Schedule, Female, Follow-Up Studies, Heroin Dependence, Humans, Male, Methadone, Patient Dropouts, Placebos, Substance Withdrawal Syndrome, Time Factors
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