Ľubomír Okruhlica; Silvia Slezáková
Inštitút drogových závislostí, Centrum pre liečbu drogových závislostí, Bratislava
Čas. Lék. čes. 2012; 151: 389-391
Background. Besides significant reduction in heroin consumption, weight gain is an accompanying phenomenon during methadone maintenance treatment. Priority of this on-going study was to find out, if it is stable, or transitory. We were also interested in possible contribution of pharmacological and socio-cultural factors on body weight changes.
Methods and Results. It was a longitudinal, clinical, observational study. The sample consisted of 42 patients from methadone maintenance treatment program (MMTP) from the Centre for Treatment of Drug Dependencies in Bratislava. Their average age was 28.6 years (SD ± 6.0); 67 % were males. The weight (kg) and body mass index (BMI) were monitored in the series of five measurements during four years period in MMTP: at treatment entry after one year, after two, after three and after four years in the program. Relationship was also explored between daily dose of methadone and BMI. The average weight of the patients and their BMI were: before the entry into MMTP 65.2 kg (SD ± 13.9) and 22.2 (SD ± 3.9); after one year 72.7 kg (SD ± 15.3) and 24.7 (SD ± 4.1); after two 75.2 kg (SD ± 16.7) and 25.6 (SD ± 4.4); after three 74.2 kg (SD ± 17.1) and 25.1 (SD ± 4.5); after four years 75.0 kg (SD ± 16.5) and 25.2 (SD ± 4.2). Significant increase of BMI was detected after one year (t = 5.03; p < 0.001) and less significant between one and two years (t = 2.5; p < 0.05) in MMTP. Significant difference was also found between proportional distributions of the patients according to BMI categories: underweight, norm, overweight, obesity; at the time of entry to MMTP and after one year in it (χ² = 13.6; p < 0.01). No any other statistically significant changes were found later on, after 1 – 4 years from the entry to the treatment. The correlation between daily dose of methadone and BMI (r = 0.273) was not significant after four years in MMTP.
Conclusions. The weight of the patients in MMTP has increased significantly after one year in the treatment, but remained stable from the second year. No substantial correlation was detected between methadone dose and BMI.
The risk of obesity and development of the metabolic syndrome as adverse drug effect is currently an important issue in the psychopharmacology. For example, the problem is frequent in the case of schizophrenia treatment with antipsychotic medications (1, 2, 3, 4). It is also discussed in the addiction medicine. Several studies (5, 6, 7, 8, 9, 10) focused on the weight gain of the patients with opioid dependence after their admission into the methadone maintenance treatment program (MMTP). In this forum we have published the findings of our previous study showing the weight gain among the people with opiod dependence after one year in methadone maintenance treatment (11). These results have discovered remarkable increase of the body mass among the patients in MMTP, but supported the hypothesis, that it was rather due to the accompanying changes of the patients´ lifestyle, then a direct side effect of the medication itself. The changes of the patients´ eating habits were becoming closer to the mainstream of the overweight general population.
However, twelve months interval should not be long enough for observation of the possible changes of the body weight, which is not the case with some other physiological functions. Also twelve months is a minimum time recommended for methadone maintenance treatment and usually it needs to be extended, sometimes for several years or lifelong. Therefore, the unanswered question of our former study was: What is the development of the body weight in the patients who are staying in MMTP for longer period of time? The main objective of the presented study was to find out what are the changes of the weight among the patients in MMTP after one, two, three and four years of continuous treatment.
It was prospective, clinical, observational study, which was an extension of our previous work (11). Smaller sample of 42 patients was selected from the former study sample of 247 patients. Only, those patients were included, who stayed in the MMTP during the whole period of prolonged monitoring for four years. The inclusion and exclusion criteria have not changed in MMTP, neither its structure, nor dosing schedule during the four years of observation. Body Mass Index (BMI) assessment was conducted within the framework of regular, complex medical check-ups every twelve months. Sample had 42 patients with average age 28.6 years (SD ± 6.0) at the time of program entry. Out of them 67 % were males and 33 % females. Together five BMI values were collected from every patient during the period of observation. Also daily doses of methadone were recorded in the same time. SPSS software was used for mathematical-statistical analysis. The study was approved by the Ethical Board.
The average weight and BMI were as it follows: before the admission into MMTP 65.2 kg (SD ± 13.9) and 22.2 (SD ± 3.9); after one year 72.7 kg (SD ± 15.3) and 24.7 (SD ± 4.1); after two 75.2 kg (SD ± 16.7) and 25.6 (SD ± 4.4); after three 74.2 kg (SD ± 17.1) and 25.1 (SD ± 4.5); after four years 75.0 kg (SD ± 16.5) and 25.2 (SD ± 4.2) (Graph 1). The weight gain was 9.1 kg in males and 11.1 kg in females after four years.
Significant difference of BMI was detected between the measurements at the admission to MMTP and after one year in it (22.2 vs. 24.7; t = 5.03; p < 0.001), but also between the values of BMI taken after one year and after two years (24.7 vs. 25.6; t = 2.5; p < 0.05).
Comparisons of BMI according to weight categories have revealed underweight in 17 % of the patients, normal weight had 59 %, overweight 8 % and obesity 2 % at the time of entry into the methadone maintenance treatment program. The shift was observed after one year: underweight had 2 %, normal weight 52 %, overweight 36 % and obese were 10 %. This change was statistically significant (χ² = 13.6; p < 0.01). Statistically significant was also difference of BMI distributions according to the weight categories in the comparisons between the values at the admission and after two years in MMTP (χ2 = 26.6; p < 0.001); after three (χ2 = 21.7; p < 0.001), and after four years from the admission into MMTP (χ2 = 23.1; p < 0.001). There were no significant changes in BMI distribution in the group of patients between the measurements after the second and the third year, and after three and four years in methadone maintenance treatment program (Table 1). 2 %, had the underweight, in the norm was 48 %, overweight 33 % and obese 17 % of the patients after four years in the end of monitoring. Spearman correlation between individual daily dose of methadone and BMI was insignificant after four years (r = 0.237).
The findings of the study are showing remarkable weight increase among the patients with opioid dependence one year after the beginning of the methadone maintenance treatment and slight increase later on, which is culminating in the second year. No significant change was observed afterwards. Consistent with our previous study (11) was the finding, that the patients with dependence had significantly lower weight before the maintenance treatment in comparison with their peers in general population.
Week correlation between the daily dose of methadone and BMI, together with the above mentioned results, would support the hypothesis that weight gain is more likely influenced by eating behaviour stereotypes, based on social and cultural factors, rather than caused by the pharmacological effect of medication. This is consistent with the Australian findings in the sample of the females treated in methadone maintenance program (12). They did not differ in BMI from the control group of women from general population, who never used the opiates. The increase of the average weight was 9.1 kg in males after four years in our study, which was close to 8.8 kg weight gain among male patients found by Kolarczyk (9). Our comparisons with general population are partially limited by the fact, that the data from general population are older. Current data from general population were not available, because survey MONIKA (13), from which we used the data in our previous study, did not continue, while our sample of the patients get older in these four years, since the beginning of the study.
Persistent, long lasting stabilization of the weight among the patients in MMTP on the higher level, when compared with the weight at the beginning of the treatment, but still being within the statistical norm of general population, does not support the hypothesis, that it could be explained by rebound hyperphagy, which was described at the beginning of so called drug-free treatment among adolescents (14).
Special attention would deserve differential diagnosis of specific oedemas as adverse effects of methadone (5, 15, 16). Their occurrence was also very rare in our practice. They were mostly associated with other somatic disorders, such as endocrine, kidney disorders and with heavy alcohol consumption. The case with oedema was not registered in our sample.
The partial limitation for generalization of our findings is the time lag of several years in between the time of our data collection and the data from the cohort from general population, which was used for comparisons with our sample. It would be also useful for the possibility of the extended interpretation of the results, to conduct weight comparisons with the patients who completed methadone maintenance treatment and are abstaining from the opiates, and also the comparison with the patients who were dependent on opiates and have been successfully detoxified during so called drug-free treatment.
Special attention deserves from the health perspective high proportion of the patients in MMTP, who were in the category of obesity. The finding indicate, that preventive or therapeutic interventions in this respect, should not be focused on the correction of medication, but on the other factors, presumably behavioural, such as eating habits and physical activity.
The findings of remarkable weight gain in our study among the patients in methadone maintenance treatment during the first year are consistent with the other authors. The weight remained stable in the following years among those who continued with treatment. Their weight did not differ from the general population. There was no significant correlation between daily dose of methadone and their body mass index. These findings are supporting the hypothesis, that with high probability the weight gain of the patients in methadone maintenance treatment is a consequence of the changes in their life style and not the result of direct adverse pharmacological effect of methadone medication.
BMI – Body Mass Index
MMTP – Methadone Maintenance Treatment Program
Address for correspondence:
MUDr. Ľubomír Okruhlica, CSc.
Centrum pre liečbu drogových závislostí
821 05 Bratislava
Fax: +421 2 5341 7475
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