Buprenorphine induced opioid withdrawal syndrome relieved by adjunctive Magnesium: A clinical trial

J Subst Use Addict Treat. 2024 May:160:209307. doi: 10.1016/j.josat.2024.209307. Epub 2024 Feb 2.

Abstract

Introduction: Precipitated opioid withdrawal syndrome (OWS) is a severe and intolerable situation that may occur by a pharmaceutical agent. Reactivation of inhibited N-methyl-d-aspartate (NMDA) receptor in person with prolonged opioid use can led to severe OWS. We conducted a double-blind, randomized clinical trial to assess the effect of magnesium sulfate (MGSO4) as an NMDA receptor antagonist on OWS.

Materials and methods: The study randomly divided forty patients with precipitated OWS due to partial agonist (buprenorphine) use referred to the emergency unit of Toxicology Department of Mashhad University of Medical Sciences, Iran; into two groups. The control group received conventional therapies, including clonidine 0.1 mg tablet each hour, intravenous infusion of 10 mg diazepam every 30 min, and IV paracetamol (Acetaminophen) 1 g, while the intervention group received 3 g of MGSO4 in 20 min and then 10 mg/kg/h up to 2 h, in addition to the conventional treatment. The clinical opiate withdrawal scale (COWS) evaluated OWS at the start of the treatment, 30 min, and 2 h later.

Results: Both groups had similar demographic, opiate types, and COWS severity at the start of the intervention. COWS was lower in the intervention than the control group at 30 min (11.20 ± 2.86 and 14.65 ± 2.36, respectively, P = 0.002) and at 2 h (3.2 ± 1.61 and 11.25 ± 3.27, respectively, P < 0.001) after treatment. The intervention group received lesser doses of clonidine (0.12 ± 0.51 and 0.17 ± 0.45 mg, P = 0.003) and Diazepam (13.50 ± 5.87, 24.0 ± 6.80 mg, P = 0.001) than the control group. Serum magnesium levels raised from 1.71 ± 0.13 mmol/L to 2.73 ± 0.13 mmol/L in the intervention group.

Conclusion: Magnesium can significantly reduce the severity of OWS. Additional studies are required to confirm these results.

Keywords: Addiction; Buprenorphine; Drug; Magnesium sulfate; Opioid; Withdrawal syndrome.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / adverse effects
  • Acetaminophen / therapeutic use
  • Adult
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use
  • Buprenorphine* / administration & dosage
  • Buprenorphine* / adverse effects
  • Buprenorphine* / therapeutic use
  • Clonidine / administration & dosage
  • Clonidine / therapeutic use
  • Diazepam / administration & dosage
  • Diazepam / adverse effects
  • Diazepam / pharmacology
  • Diazepam / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Iran
  • Magnesium Sulfate* / administration & dosage
  • Magnesium Sulfate* / adverse effects
  • Magnesium Sulfate* / pharmacology
  • Magnesium Sulfate* / therapeutic use
  • Male
  • Middle Aged
  • Opioid-Related Disorders / drug therapy
  • Substance Withdrawal Syndrome* / drug therapy
  • Young Adult

Substances

  • Buprenorphine
  • Magnesium Sulfate
  • Clonidine
  • Analgesics, Opioid
  • Acetaminophen
  • Diazepam

Associated data

  • IRCT/IRCT2019207042648N1