This study found that the relapse risk of newly-enrolled participants may increase with the treatment duration and risk factors differed between those who received 6-month and 12-month consecutive treatment. We also assessed the relapse risk of participants under different situations and identified high-risk groups for each treatment duration.
It is believed that the maximum effectiveness of MMT starts to show up at least after 12 months2, therefore, participants tend to drop out or relapse at the early stage because of withdrawal symptoms, side effects, and a strong craving for drugs34. Previous research found that most relapses happened in the first 6-month treatment 12 and this was confirmed by our study.
Relapse is a multifactorial outcome35, and factors such as sex, marital status, living status, the relationship with family, and drug use behavior have been proved to be correlated with it12,16,36,37. In this study, we provide evidence that these factors were influential for participants who completed 6-month MMT. To be more detailed, Living alone or being estranged from family and friends might indicate that the participants received little social support, which makes them more likely to drop out and relapse38,39. This could be more apparent among Chinese participants due to their culture40. Additionally, previous drug-use habits are associated with relapse as well38. People who use drugs more frequently before MMT and exhibit high-risk behaviors such as syringe sharing might feel difficult to adapt to the substitution of methadone. Severe withdrawal symptoms could also lead them to return to heroin use 41. The daily methadone counts for relapse as well, especially at the initial stage of MMT12,42. Komasi et al.’s12 found that participants who relapsed during the first 6-month MMT reported more dose non-satisfaction than those who did not. A low methadone dose is a leading risk factor for relapse and could hinder the effectiveness of MMT. In this study, participants who took less than 30mg of methadone per day during the first 6-month had the lowest retention and the highest relapse risk. Therefore, we suggest conducting interventions about family engagement and in-time dose adjustment for those who are at the early stage of MMT.
However, the effects of these factors will be fading with the treatment duration in line with our findings. Several possible reasons could be the explanation. First, pleasant family relationships and seldom communication from drug friends after participation could engage the compliance. These might be common characteristics that those who insisted on MMT for a long time shared43, leading to the insignificant difference between relapse and non-relapse groups. Second, the craving for drugs would decrease with treatment. Therefore, previous drug-use behaviors might gradually become less of a determinant for those with longer treatment duration. Finally, those who were treated for 12-month might have been taking an appropriate dose at the beginning of the treatment, which helps them with a quick adaption.
In contrast, age, the age at the initial drug use, the HIV infection status, sexual behavior, and continuous treatment days had long-lasting effects on relapse, regardless of the treatment duration. Among these factors, age and age at the initial drug use reflect the severity of the drug addiction history. A long addiction history is usually related to a high risk of relapse, and this has been reported in participants at different stages of treatment40,44. Adjusting to new behaviors might be harder for those who were addicted to heroin since a younger age 45. Also, unprotected sex and multiple sexual partners could cause HIV infection and decrease compliance with MMT46. Some antiretroviral medications can reduce the potency of methadone47, which makes HIV-positive participants more vulnerable to relapse. Additionally, short continuous treatment days indicate poor adherence, of which relapse is always a dominant cause 19,48. Our findings are consistent with the above-mentioned conclusions and we, therefore, suggest implementing health education for preventing HIV/STI and anti-narcotics in the whole process of treatment to promote adherence and reduce the relapse rate.
We also identified the groups with the highest relapse risk for both durations. Among those who persisted with 6-month MMT. Participants who aged younger than 30, being HIV-positive, with addiction to drugs since their teenage years, communicated with friends more than once a day, and had poor family support, would have the highest possibility of relapse (66.7%). However, the highest-risk group among those who received a 12-month MMT was HIV-negative participants who were in their 30s and did not use drugs for that long time but had once dropped out. They were predicted to have a relapse risk as high as 83.3%.
Apart from those, we found that participants who received MMT for a longer time are generally at a higher risk than those of a shorter term. The evidence is that participants who received 6-month MMT would only take half of the relapse risk when they were under the same condition as the highest-risk group after 12-month MMT. This might be because the occurrence of relapse during the first 6-month treatment was associated with many other factors, thus, the effects of common factors might be weakened. The increasing relapse risk along with the treatment duration could be another explanation16.
There are also some highlights in this study. For example, we found that those who drove or needed less than 10 minutes to reach the clinic were more possible to relapse than other participants. Theoretically, the long-distance and traveling difficulties to the clinic would reduce the adherence of MMT 49,50. However, the high accessibility such as living too close to the clinic means having the flexibility in choosing the timing to get there, which might decrease the adherence as well. Additionally, being capable of driving indicates that participants might have a relatively sufficient income or a decent life. It is more possible for these people to afford drugs, compared to those who were less paid.
Another unexpected finding is that it was farmers, rather than the unemployed, that were most vulnerable to relapse. A rational interpretation could be that, unlike those who live in towns, people who live in rural areas might have poorer accessibility to MMT services. Research conducted in Thailand showed that rural residents faced barriers to utilizing MMT services, including missing the opening hours of clinics and the unaffordable cost of travel51. The Global State of Harm Reduction 20201 has highlighted that rural communities were underserved by harm reduction services and this geographical gap has hindered the implementation of MMT among rural residents, including farmers. Hence, more adaptive operations are required to improve the accessibility of MMT for this group.
Several limitations exist in this study. First, we did not include factors related to psychology and neurobiology 52, due to the limited content of the questionnaire. These factors are also critical and worth to be explored in the future. Second, all the participants were native residents of Guangdong Province, thus, more consideration will be required when generalizing our findings to other contexts. Third, the smaller sample size and fewer selected variables of the 12-month model than the 6-month model might have made the former less discriminative, leading to the lower AUC. The model performance needs to be improved when we could assess more data.