Table 3.
Pooled all cause and overdose mortality rates during periods in and out of opioid substitution treatment with methadone by study characteristics
| Study characteristic | All cause mortality rate/1000 person years (95% CI)* | Overdose mortality rate/1000 person years (95% CI)* | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| No of studies | In treatment | Out of treatment | P value† | I2 (%)‡ | No of studies | In treatment | Out of treatment | P value† | I2 (%)‡ | ||
| Location: | |||||||||||
| Europe/Israel | 9 | 13.9 (9.5 to 20.5) | 46.6 (29.0 to 74.9) | 0.08 | 98 | 7 | 3.1 (2.4 to 4.0) | 13.3 (5.9 to 29.8) | 0.13 | 93 | |
| North America | 4 | 11.2 (6.4 to 19.6) | 42.3 (21.2 to 84.6) | 2 | 2.3 (1.4 to 3.8) | 20.5 (4.4 to 94.5) | |||||
| Australia | 3 | 6.3 (3.3 to 12.1) | 14.0 (6.3 to 30.8) | 2 | 2.0 (1.4 to 2.9) | 6.7 (1.5 to 29.6) | |||||
| Opioid injectors (%): | |||||||||||
| <100 | 12 | 9.0 (6.9 to 11.7) | 25.8 (18.7 to 35.5) | 0.001 | 95 | 10 | 2.5 (2.0 to 3.0) | 10.6 (6.1 to 18.5) | — | — | |
| 100 | 4 | 23.4 (14.2 to 38.5) | 109.9 (59.4 to 203.4) | 1 | —§ | —§ | |||||
| Men (%): | |||||||||||
| <75 | 11 | 9.5 (6.9 to 13.2) | 30.0 (18.4 to 48.8) | 0.67 | 98 | 6 | 2.4 (1.8 to 3.4) | 10.6 (4.5 to 24.8) | 0.74 | 93 | |
| ≥75 | 3 | 11.6 (6.1 to 22.0) | 45.9 (17.8 to 117.9) | 5 | 2.9 (2.0 to 4.2) | 15.8 (6.2 to 40.3) | |||||
| Mean age (years): | |||||||||||
| <35 | 10 | 9.9 (6.8 to 14.5) | 29.3 (17.9 to 48.2) | 0.40 | 98 | 8 | 2.6 (1.9 to 3.5) | 10.6 (5.2 to 21.8) | 0.60 | 93 | |
| ≥35 | 6 | 14.0 (8.7 to 22.7) | 50.3 (26.8 to 94.3) | 3 | 2.7 (1.5 to 4.7) | 20.5 (6.2 to 67.6) | |||||
| Average methadone dose (mg/day): | |||||||||||
| ≤80 | 7 | 9.6 (6.3 to 14.8) | 26.9 (15.5 to 46.5) | 0.56 | 92 | 5 | 3.1 (2.0 to 4.6) | 10.3 (4.0 to 26.9) | 0.22 | 93 | |
| >80 | 5 | 9.9 (6.0 to 16.5) | 35.4 (18.5 to 67.7) | 5 | 2.5 (1.6 to 3.9) | 17.0 (6.5 to 44.9) | |||||
| Inpatient induction (%): | |||||||||||
| 0 | 9 | 9.2 (6.3 to 13.6) | 29.9 (17.3 to 51.6) | 0.19 | 98 | 7 | 2.5 (1.8 to 3.4) | 10.0 (4.5 to 22.3) | 0.65 | 93 | |
| >0 | 6 | 15.4 (9.3 to 25.3) | 45.9 (22.9 to 92.1) | 3 | 2.9 (1.7 to 5.0) | 18.4 (5.4 to 62.5) | |||||
| Treatment provider: | |||||||||||
| Specialist | 10 | 13.4 (9.2 to 19.5) | 46.5 (28.2 to 76.5) | 0.26 | 98 | 7 | 2.5 (1.7 to 3.7) | 20.8 (11.1 to 38.8) | 0.01 | 88 | |
| GP/mixed | 6 | 8.6 (5.4 to 13.7) | 24.4 (13.1 to 45.4) | 4 | 2.4 (1.6 to 3.6) | 5.6 (2.5 to 12.5) | |||||
| Midpoint follow-up period: | |||||||||||
| <2000 | 10 | 12.6 (8.5 to 18.7) | 38.8 (22.8 to 66.1) | 0.58 | 98 | 7 | 2.8 (2.0 to 3.9) | 15.4 (7.0 to 33.9) | 0.67 | 93 | |
| ≥2000 | 6 | 9.7 (6.0 to 15.9) | 32.0 (16.5 to 62.3) | 4 | 2.4 (1.7 to 3.5) | 9.0 (3.2 to 25.2) | |||||
| Loss to follow-up (%): | |||||||||||
| <10 | 12 | 11.9 (8.3 to 17.0) | 38.3 (23.7 to 61.9) | 0.81 | 98 | 8 | 2.5 (1.9 to 3.2) | 9.8 (5.0 to 19.5) | 0.33 | 93 | |
| ≥10 | 4 | 9.5 (5.0 to 18.0) | 31.3 (13.5 to 72.3) | 3 | 3.2 (1.7 to 6.0) | 25.4 (8.1 to 79.4) | |||||
*Pooled mortality rates and 95% confidence intervals during periods in and out of treatment by study characteristics estimated from separate bivariate random effects meta-regression models relating log transformed rates in both treatment periods with each study characteristic.
†Overall P value for heterogeneity of pooled mortality rates across categories of study characteristic, as obtained from likelihood ratio test comparing nested meta-regression models with and without study characteristic fitted via maximum likelihood.
‡Overall I2 statistic for residual heterogeneity in study specific mortality rates not explained by corresponding study characteristic.
§Pooled mortality rates not applicable to categories with single study.