Aims and objectives

In this WP, we aim to investigate how OST delivery has changed over time, in terms of:

• number of OST patients and episodes by OST type
• patient characteristics such as age, gender and medication prescribed
• episode characteristics such as mean and maximum dose and duration.

Details of the starting and ending doses are considered in Chapter 7.

Data set

The data used in these analyses were restricted to episodes in which some part of treatment occurred during the study period. To obtain a more accurate picture of the trends in these data, we considered all episodes including those involving dihydrocodeine or more than one medication and all patients ignoring the age restriction used in other WPs (see Figure 2). This led to the data for 12,780 patients and 34,427 episodes being analysed.

Prevalence of opiate substitution treatment

Crude UK prevalence estimates were derived from valid OST patients within each year and the total number of patients within CPRD. To obtain adjusted prevalence estimates, it was necessary to estimate the number of OST patients for the UK. This was achieved by combining numbers of patients for each country, taking into account the different coverages for each country by CPRD.

Patient characteristics

These outcomes include age and gender demographics and the medications prescribed. Medications included not only the three OST medications but also benzodiazepines, z-drugs and gabapentinoids. The last three medications were considered to be prescribed only during valid periods for each patient.

Episode characteristics

Mean and maximum doses were considered as outcomes. These are reported by year for episodes involving only methadone or buprenorphine. Average doses were calculated daily for the parts of episodes within any given year. Maximum doses were reported as a percentage of episodes with ≥ 60 mg for methadone or ≥ 12 mg for buprenorphine. The last episode for each patient was excluded if treatment was ongoing at the time follow-up ceased. This reduced the episode count to 31,260. For this outcome, episodes were valid only for the year associated with the maximum dose.

In addition, on- and off-treatment duration were investigated. Episode treatment was considered to cease when there was a gap of > 28 days between the end of one prescription and the start of the next. Last episodes were right-censored by the death of the patient, the last CPRD data collection date or the end of the study. First episodes were potentially left-censored by the practice up-to-standard date, the start of patient follow-up (registration with a CPRD practice) or the study start date.

Statistical analysis

A number of different analyses were used to assess trends depending on the particular outcomes. The prevalence of OST was analysed using Poisson regression. Binary outcomes (gender, medications and dose criteria) were analysed using logistic regression. Trends in duration were analysed using survival analysis to take account of censoring. Different parametric distributions were compared to find the best fit (Table 1). These analyses suggested that the log-normal distribution was superior, although other distributions gave similar results. Other outcomes, namely age and mean dose, were analysed using linear regression.

TABLE 1

Comparisons of parametric survival functions for the analysis of duration

Primary analyses involved unadjusted year effects. Trends were assessed in two ways. First, a linear year effect was fitted to the data. Second, a deviation statistic was calculated. This reflected twice the difference in log-likelihoods between a model treating year as a factor and the linear model. The derived statistic [15 degrees of freedom (df)] provided evidence of any non-linearity. Where the analysis involved linear regression, the trend is additive from one year to the next. For other analyses, there is an implicit log transformation making the trend a multiplicative effect from one year to the next when back transformed.

Trends in prevalence of opiate substitution treatment

Most countries in the UK showed similar trends in that OST prevalence rates and number of patients were increasing at the start of the study and declining by the end (Table 2 and Figure 3), although for Northern Ireland, where the use of primary care to treat problem drug use is more limited, these data were underpowered to detect the possible inverted U-shaped trend. The observed maxima varied by country and ranged between 2008 and 2011 for three nations, with Scotland showing an earlier peak, in 2003. Overall, the UK showed a maximum in 2008. Perhaps as expected, the adjusted UK estimates were similar to the unadjusted estimates because of the major contribution of England to the UK total.

TABLE 2

Prevalence of OST by country and year

FIGURE 3

Prevalence of OST by country and year. All countries except Northern Ireland showed non-linear trends in the prevalence of OST by year. The non-linearity reflected an increasing trend in the earlier years followed by a decline in the prevalence. The timing (more...)

Trends in patient characteristics

The average age of OST patients increased by 10 years during the study (Table 3). About half of this increase was attributable to an ageing sample of patients receiving prolonged OST over many episodes. There was little evidence that the gender ratio varied during the study period. However, this concealed a declining trend in the ratio for the under-30-year-olds, with men representing 70% of this group in 1998 compared with 60% in 2014 (p < 0.0001).

TABLE 3

Patient characteristics by year

During the study, the use of methadone, dihydrocodeine and benzodiazepines was decreasing while the use of buprenorphine and gabapentinoids was increasing (Figure 4). Deviations from linearity for methadone and buprenorphine suggested that the major changes occurred up to 2006, with less evidence of any changes after that date. Although there was evidence of a declining prevalence for the prescription of z-drugs, the effect size was small, reflecting a prevalence among OST patients of ≈12. Considering the prevalence of any of these three medications, the prevalence was declining up to 2002 but with no strong evidence of any change after that year. Overall, 78.6% [95% confidence interval (CI) 77.9% to 79.3%], 36.0% (95% CI 35.2% to 36.9%), 15.4% (95% CI 14.7% to 16.0%), 47.4% (95% CI 46.6% to 48.3%), 25.4% (95% CI 24.6% to 28.1%) and 9.2% (95% CI 6.7% to 9.7%) of patients were prescribed methadone, buprenorphine, dihydrocodeine, benzodiazepines, z-drugs or gabapentinoids, respectively.

FIGURE 4

Opiate substitution treatment medications, benzodiazepines, z-drugs and gabapentinoids prescribed to OST patients by year. Overall, during the study, prescriptions of methadone declined, whereas those for buprenorphine increased. There may be some evidence (more...)

Trends in episode characteristics

Overall, average dose increased during the study, although there was evidence that this trend may have changed after 2008 (Table 4). Linear trends after this date showed a decreasing effect, with –1.057 (95% CI –1.123 to –0.966) and –0.151 (95% CI –0.177 to –0.126) for methadone and buprenorphine, respectively. Both medications showed an increasing adherence to guidelines with optimal dose across the whole study. However, the deviation statistics suggested a more complex pattern. After 2008, methadone episodes showed a declining adherence, multiplicative trend (0.96, 95% CI 0.94 to 0.99), whereas buprenorphine showed no trend (1.02, 95% CI 0.99 to 1.06).

TABLE 4

Episode characteristics by methadone or buprenorphine episodes and by year

The predicted median durations by year are shown in Table 4. The mean durations are not reported because of the skewed nature of the distribution. On-treatment duration reached a maximum in 2010 for methadone (Figure 5). By contrast, duration for buprenorphine was still increasing by the end of the study. Off-treatment durations were generally increasing throughout the study but there were periods when duration appeared to be constant. For methadone, there was no evidence of any increase before 2009 (HR 1.01, 95% CI 1.00 to 1.02; p = 0.180). Similarly, for buprenorphine, during the period 2002–8, off-treatment duration remained constant (HR 1.01, 95% CI 0.99 to 1.03; p = 0.306).

FIGURE 5

Duration of OST by type and year. The median duration of buprenorphine treatment increased overall during the study, although there was some variability in the early years owing to the small number of episodes. Methadone episodes showed an increasing (more...)

The associations of gender, age, comorbidity and region with on- and off-durations are reported in Table 5. Age and gender were associated with on-treatment duration for buprenorphine only, with older women tending to have longer durations (lower HR). Those with comorbid chronic illnesses tended to have longer durations for both medications. For off-treatment duration, gender had no association with either medication and comorbidity had no association with buprenorphine. Older patients tended to have longer intervals between treatments. Adjusting for these variables did not markedly change the duration results (Table 6).

TABLE 5

Effect of confounders for on- and off-treatment duration by OST type

TABLE 6

Median episode duration by year and type of medication adjusted for four confounders

In a sensitivity analysis, we also analysed duration using the start year of on or off treatment rather than each year associated with an episode. This had two consequences: (1) episodes with on/off treatment starting before the study start date were excluded and (2) an episode contributed to only 1 year however long the period on/off treatment. As a result, it was appropriate to consider each episode as only a single record. Despite these changes to the data, the median durations were very similar (Table 7).

TABLE 7

Median episode duration by start year and type of medication

Summary

Our data suggest that the prevalence of OST has been declining since 2010. Extrapolation to the whole UK suggests that < 50,000 patients are currently being treated in primary care. This number is lower than other estimates^9,11 and may reflect either other patients being treated by alternative services such as community drug agencies or that CPRD practices were not representative of all UK general practices.

Trends in medications suggest that prescribing buprenorphine has become more prevalent, with about 30% of patients in 2014 prescribed this medication. Co-prescription of gabapentinoids was rare at the start of this study but by the end it was prescribed to about 13% of patients. Benzodiazepines were more commonly co-prescribed but the prevalence of this medication among OST patients per year declined, although they were still prescribed to about 26% of patients by the end of the study. The prevalence of co-prescription of z-drugs changed very little during the study.

The mean doses and the proportion of treatment episodes reaching an optimal dose increased up to about 2008, with evidence of declining trends after this date for most outcomes. The exception was optimal dose for buprenorphine for which the evidence suggested a stable proportion post 2008. Shorter treatment duration for buprenorphine than for methadone treatment has also been reported in other studies.^{16,21–23,63} Off-treatment durations increased for both methadone and buprenorphine after 2008. It is interesting to note that the shorter on-treatment duration for buprenorphine was associated with a shorter off-treatment duration.