Adapting Opioid Therapy: Transition from Methadone to Slow-Release Morphine Amid COVID-19 Supply Chain Disruptions

Background:
In January 2022, disruptions due to COVID-19 halted methadone supply at the Republican Centre for Addictive Disorders in Lithuania, affecting 252 patients. They were temporarily transferred to slow-release oral morphine (SROM) before returning to methadone after two weeks. This study aims to evaluate the impact of this switch on opioid maintenance therapy and determine the effective methadone-to-morphine dose ratio.

Methods:
In a retrospective study, data from 231 individuals transferred from methadone to SROM for at least two days were analysed. Initially, SROM was prescribed at a 1:4 ratio to methadone, with subsequent dose adjustments. Variables included withdrawal severity, time for SROM dosage stabilization, methadone to SROM ratio, post-transfer methadone dosage consistency, and patients' program retention (1, 3, 6, and 12 months). Data comparisons considered patient groups by gender, methadone dosage (low: 10-60 mg/d, medium: 61-100 mg/d, high: 101-150 mg/d), and clinic attendance frequency.

Results:
Mean SROM treatment duration was 8.4 days (min 2 – max 13). On average, the SROM dose was stabilized after 4.2 days (SD 2.60). The most severe withdrawal symptoms occurred on average after 3.2 days (SD 1.95), with the highest recorded COWS (Clinical Opioid Withdrawal Scale) scores averaging 8.2 (SD 4.41). The mean of the final methadone to SROM ratio was 1:5.23 (SD 1:1.27). Remarkably, 97.8% of patients remained in the Methadone program after 1 month, 95.7% after 3 months, 91.8% after 6 months, and 89.2% after 12 months. During the transfer process, one unrelated fatality occurred. For 87% of patients returning to methadone, the dosage remained unchanged.

Comparing results by gender, women reported more severe withdrawal symptoms (mean 9.5 vs. 7.8; p=0.01).

Based on methadone dispensation, patients visiting the clinic daily were less likely to stay in the Methadone program long-term than those with take-home doses (87% vs. 97% after 6 months, p<0.01, and 83% vs. 97%, p<0.01). The effective SROM dose was reached later for daily clinic visitors (4.5 vs. 3.7 days, p=0.02). No statistically significant differences were found in other variables.

Results by methadone dosage showed that individuals with low doses reported lower maximum COWS scores than those with medium and high doses (6.1 vs. 8.9 and 8.7, respectively; p<0.01) and reached the effective SROM dosage more quickly (3.3 vs. 4.4 and 4.4 days, respectively; p=0.01). After 6 months, 84%, 93%, and 100% of patients with low, medium, and high methadone doses, respectively, remained in the program (p=0.02). No significant differences were found in other variables.

Conclusions:
Switching to SROM can be an effective strategy to manage methadone supply disturbances, causing minimal short- and long-term disruptions and inconveniences for patients. In our study, the effective methadone to SROM dosage ratio was 1:5.2, smaller than ratios reported in other studies ranging up to 1:18.2.