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Effect of oral naloxone on opioid-induced constipation in methadone maintenance treatment patients, a double-blind, placebo-control, clinical trial

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Abstract

Background

Opioid-induced constipation (OIC) is the most prevalent side effect of methadone maintenance therapy (MMT). Naloxone could reduce the OIC.

Method

Fifty-six MMT cases (< 75 mg/day methadone, > 3 months) were entered randomly into four groups of a trial. They received placebo or naloxone tablets (0.5, 2, or 4 mg/day) once a day for 2 weeks. They continued their conventional laxative. Their constipation and opiate withdrawal (OWS) were evaluated by the Bristol Stool Form Scale (stool consistency and frequency), Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire, Constipation Scoring System (CSS), and the Subjective Opiate Withdrawal Scale (SOWS) before starting treatment and at the end of the first and second weeks.

Results

The dose of 4 mg/day naloxone was excluded from the study due to severe OWS. The precipitants of groups had similar ages, methadone dose and duration, laxative use, and constipation scores at the start of the trial. However, 2 mg of naloxone could change the stool consistency (PV = 0.0052) and frequency (P = 0.0133), 0.5 mg/day dose only improved the stool consistency (P = 0.0016). The patients’ CSS and PAC-SYM scores were reduced by naloxone after the 1st week of treatment. However, there was no significant difference in the mean score of SOWS at different assessment times and groups. Also, 3 and 4 cases of 0.5 and 2 mg/day groups, respectively, withdrew from the study due to OWS.

Conclusion

Oral naloxone at doses of 0.5 and 2 mg/day was significantly more effective than placebo on OIC in MMT. However, the dose of 4 mg induced intolerable OWS.

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Data availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Acknowledgements

The data reported in this article are part of a Pharm D. thesis. The researchers especially thank the participants who were included in the study. We also thank the eight addiction treatment centers of Khorasan-Razavi.

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Authors and Affiliations

  1. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Shaghayegh Akhgarandouz

  2. Medical Toxicology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Moshiri, Leila Etemad & Bita Dadpour

  3. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Leila Etemad

  4. Community medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Majid Khadem-Rezaiyan

  5. Department of Pharmacodynamics and Toxicology, Mashhad University of Medical Sciences, Mashhad, Iran

    Nasser Vahdati-Mashhadian

Authors
  1. Shaghayegh Akhgarandouz
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  2. Mohammad Moshiri
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Contributions

Shaghayegh Akhgarandooz: data curation and writing—original draft; Mohammad Moshiri: conceptualization, methodology, software, formal analysis, and writing—review and editing; Bita Dadpour: writing—review and editing; Majid Khadem-Rezaiyan: writing—review and editing, methodology, and formal analysis; Leila Etemad: conceptualization, methodology, and writing—review and editing; Nasser Vahdati-Mashhadian: writing—review and editing, supervision, funding acquisition, and corresponding. All authors reviewed the results and approved the final version of the manuscript.

Corresponding author

Correspondence to Nasser Vahdati-Mashhadian.

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Akhgarandouz, S., Moshiri, M., Etemad, L. et al. Effect of oral naloxone on opioid-induced constipation in methadone maintenance treatment patients, a double-blind, placebo-control, clinical trial. Ir J Med Sci (2024). https://doi.org/10.1007/s11845-024-03652-2

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