The 12-year mortality rate in the present study was 8% and average annual mortality rate was 0.7%. Mortality rate was lower than in other studies (3
). The 12-month mortality rate in a long-term study in primary care and specialized substitution centers in Germany was 1.1% (11
A failure to achieve remission despite previous methadone treatment at the start of the study represented the strongest predictor of fatal outcome in this study. Additionally, the plan to undergo methadone maintenance treatment at the start of the study was also a predictor of the fatal outcome. This indicates that patients at risk for fatal outcome were the patients with more severe opioid dependence, as previously reported (12
). It could be expected that the severity of the opioid dependence would also be reflected by the daily methadone dose (14
). However, there was no significant difference between the groups in the daily methadone dose administered either at the beginning or at the end of treatment. These findings could be partially explained by the Croatian treatment model: implementation of treatment primarily in non-hospital settings characterized by a high degree of accessibility to care, which had to be balanced with relatively lower methadone doses in order to assure safety of the treatment in the out-patient setting (8
). To support this thesis, the endpoint methadone dose in this study was 50 mg for both groups of patients, which was lower than the daily methadone dose required for stable maintenance, which ranges from 60 mg to 100 mg, as recommended in the literature (15
The practical implication of our research is that the family physician who is initiating methadone substitution therapy for a new opioid dependent patient should analyze the results of the previous therapeutic attempts, since the failure of previous methadone therapy can be considered as a risk factor for a fatal outcome. In the Croatian shared care model, the decision on the planned treatment modality (detoxification or maintenance therapy) is made by the psychiatrist, with the family physician having a less active role. Nonetheless, patients treated with maintenance therapy should also be considered by the family physician as patients under higher risk for fatal outcome. Family medicine is a suitable context for patient-centered approach, ie, recognizing individual risk factors in opioid dependent patients in care (17
). We might conclude that patients in whom maintenance therapy is planned should be more intensively monitored by their family physicians, as would patients with any other severe chronic disease.
The lack of family physician’s assessment of the patient’s drug use status due to loss of contact represented the second strongest predictor of fatal outcome. This finding reveals the importance of family physicians’ insisting on compliance and adequate intervention in case of contact loss with the patient. The family physician has to continuously assess the drug use status of methadone-treated patients and, if they fail to attain abstinence or their management is impossible, consider their referral to the psychiatrist in order to revise the therapeutic plan. It is important to point out that during the study period family physicians lost contact with only 8.3% of the surviving patients and 30.4% of the deceased ones. In similar surveys from other countries, the continuity of care was significantly worse. Since retention in the treatment program is a key indicator of methadone treatment success (18
), this fact indicates a high quality of care in the family medicine setting in Croatia. A study in Ireland reported that 61% of patients included in methadone treatment remained in continuous treatment for more than 1 year, and those who were treated by a specialist were twice as likely to leave methadone treatment in 1 year than those who were treated by a primary care physician (18
Previous studies suggested that the key features of a successful method of retaining opioid users in treatment are an adequate methadone dose and easy access to the primary care physician (18
). Our study supports the approach of treating patients with opioid dependence in the same way as patients with any other chronic disease (20
). Family physicians are particularly important for such a treatment since continuity of care is central to family physicians’ everyday work, especially in treating chronic patients from vulnerable and socially deprived groups (21
Living in an unstable relationship represented the third strongest predictor of fatal outcome in this study. However, it is not clear whether this observation is connected with severity of the illness at the time of first evaluation or whether living in an unstable relationship increases the risk of other, unrecognized medical conditions that might increase the possibility of fatal outcome. The significant relationship between family background and opioid dependence development is well known (23
). A recent 12-year follow-up study of patients in methadone treatment observed that moderate and long-term recovery was associated with fewer relationship disruptions (24
). Our findings should therefore serve as an incentive to family physicians to monitor and motivate harmonious family functioning.
There was no significant difference between the groups in drug consumption profile at the beginning of methadone treatment. This finding might be explained by a sudden huge rise in drug supply and demand in Croatia in the mid-nineties (8
). The male to female ratio in the study was 4.2 to 1, which is in line with the sex ratio in national and international observational studies (25
), suggesting that our group was representative of the studied population. Our patients abused heroin for 5 to 6 years before the beginning of therapy, while the European Monitoring Centre for Drugs and Drug Addiction Annual Report for the year 2008 found this period to be on average 8 years (26
). The relatively early beginning of treatment of patients observed in this study could have contributed to better results for continuity of care. The time between the onset of drug abuse and start of treatment represents the time frame in which family physicians play an indispensable role in the early detection of opioid dependence, as well as in motivating patients with opioid dependence to undergo treatment.
There was no significant difference between the groups in the method of methadone therapy administration in the last study year for surviving patients and in the year before death for deceased patients. These findings suggest that adherence to the standardized procedures for methadone therapy administration, implemented both by patients and their family physicians, improved patients’ safety (15
One of the study limitations is the sample size. The total number of participants in the deceased group was too small to examine the association between the mortality risk and other factors. Second, there are several methodological concerns. As in similar studies, the use of proxy informants, retrospective data collection, lack of blinding regarding case and comparison participants, and the potential impact of opioid dependence and the stigma of opioid dependence on reporting may have influenced the reliability of the data. Also, our strategy of scheduling interviews with patients could have increased the risk of recall bias. The data should be interpreted having these limitations in mind.
In conclusion, the observed risk factors should be taken into consideration by family physicians in their everyday work with opioid-dependent patients treated with methadone.