Introduction
Attention-deficit hyperactivity disorder (ADHD) is now accepted to be a condition which can persist throughout life. Follow-up studies suggest that up to three-quarters of young people diagnosed as children continue to experience symptoms into adulthood, even if they no longer meet full diagnostic criteria [
1]. These symptoms, which include inattention, impulsivity, and hyperactivity, can undermine the fulfilment of adult responsibilities such as further education, employment, intimate relationships and parenting, and are associated with risk-taking behaviours, accidents and injuries [
2‐
5].
Consequently, much recent research has focussed on ADHD management during the transition to adulthood, and in particular on the prescription of ADHD medication. In studies from the UK, USA and Europe [
6‐
9], the proportion of young people stopping medication during this period appears to be in excess of the proportion expected to be symptom free from follow-up studies [
1]. For those with ongoing symptoms, cessation of medication is likely to represent a complex combination of choice and circumstance. During adolescence, young people are expected to become involved in decision making about their treatment and may experiment with starting and stopping medication and with alternative coping strategies [
10‐
12]. Medication is also often perceived as an intervention intended to allow the young person to cope with school and once examinations are finished, the adverse effects may be seen to outweigh the benefits [
12‐
14]. External factors may influence ongoing prescribing, such as a lack of services or expertise to oversee medication management in adults, or a lack of support, resource and preparation for transition to adult services that leads both services and young people to disengage even before the age boundary for the service is reached [
14‐
16].
Stopping medication can have positive outcomes for many young people, but for others, cessation may be detrimental and destabilising at a vulnerable life stage. Arguably, we would therefore expect to see a prescribing pattern whereby some adolescents with continuing symptoms stop medication but later seek to restart treatment as young adults. Guidance from the UK National Institute for Health and Care Excellence (NICE) now recognises that people with ADHD previously treated as children may return to services after the age of 18 years, seeking support and treatment for continuing ADHD symptoms [
17].
This group of young adults who do not undergo transition into an adult service for their ADHD but then seek to re-enter services and potentially resume treatment have been little studied to date. Therefore, there is a gap in knowledge about the scale and needs of this group, which is important for planning services and training. Very few studies have examined the patterns of resumption amongst young people previously prescribed medication. Notably, whilst the USA-based large multimodal treatment of attention-deficit hyperactivity disorder (MTA) trial reported on ‘stopping and restarting’ patterns in adolescents, it has not published data on resumption after the age of 18 years [
12]. In the UK, Wong et al. described resumption in the General Practice Research Datalink from 1999 to 2006 amongst patients who had stopped after the age of 15 years [
18]. Only 56 of the 407 individuals who stopped restarted treatment during the follow-up period, the majority in the first year after cessation; however, this study took place prior to the publication of the first UK NICE ADHD guidance that referred to adults in 2008 [
19].
We aimed to explore resumption of ADHD medication prescriptions in early adulthood (from age 20 onwards) amongst young people whose prescriptions stopped in adolescence (aged 14–18 years) using primary care prescribing data from the UK Clinical Practice Research Datalink from 2005 to 2013. The age range of 14–18 years for cessation was chosen as it corresponds to adolescence and the period of preparation for transition to adult health-care services; this is the time at which young people are most likely to cease their ADHD medication [
8,
9]. We studied resumption from the age of 20 onwards, to capture prescribing in adult services rather than extended prescribing in child services.
Our chief research questions were:
What proportion of young people who have previously been prescribed ADHD medication and stopped resume prescriptions in early adulthood, and what is the probability of resuming medication from age 20 years onwards?
What background characteristics are associated with resumption?
Methods
Study design
This study was a secondary analysis of data from the Clinical Practice Research Datalink (CPRD), a large UK clinical database run by the Medicines and Healthcare Products Regulatory Agency (MHRA). The primary care section of the database contains the records of over 11 million patients and is contributed to by more than 670 GP practices across the UK, covering over 6% of the population [
20]. CPRD uses software to extract anonymised data from participating practices’ IT systems. Records of each patient are coded by GPs and practice staff according to NHS coding schemes, and all primary care-issued prescriptions are automatically captured. All protocols using patient-level data from the CPRD are reviewed and approved by the Independent Scientific Advisory Committee on behalf of the National Research Ethics Service Committee. This study protocol (13_213) was granted approval in 2013.
Patients
The sample for this analysis used a subset of a larger dataset of patients (
N = 9390) with a recorded diagnosis of ADHD using NHS coding schemes (described in Newlove-Delgado et al. [
9]). Recorded psychiatric diagnoses were identified using CPRD medical codes and READ term codes used in UK primary care, which map to ICD-10 categories [
21]. Psychotropic prescribing (including for ADHD medication) was categorised using CPRD product codes referring to British National Formulary categories [
22]. The dataset included patients aged between 10 and 20 years in 2005, and the study period ran from 1 January 2005 until 31 December 2013.
To be included in this analysis, patients had to:
Have at least 1 year’s worth of prescribing records for an ADHD medication, to ensure this was a regular prescription and not a ‘trial’ of medication.
Have their last recorded prescription for an ADHD medication issued between the ages of 14 and 18 years (inclusive); with no further ADHD prescribing recorded until the age of 20 years if at all.
Have at least 1 year’s worth of follow-up data in the CPRD from the age of 20 years.
Analysis
Resumption was defined as having at least one recorded prescription of ADHD medication at the age of 20 years or over. We reported the percentage of included cases who resumed prescriptions and the age of restarting, and the percentage of those who resumed prescriptions by age at stopping. The percentage of those who resumed medication was then reported by key characteristics (gender, non-ADHD prescription status, recorded referral to adult mental health services and non-ADHD psychiatric diagnoses). We also reported the prescription of non-ADHD psychotropic medication in individuals who did and did not resume ADHD prescriptions and used the Chi squared test to compare the proportions.
We then performed survival analysis to examine the time to resumption of ADHD prescriptions. The observation period for the survival analysis began from the year of the case’s 20th birthday and continued until a new prescription for an ADHD medication was recorded (resumption), until records for the patient were no longer available or the study period ended (31 December 2013)—i.e., they were censored. The median time to resumption was reported and the distribution of time to resumption was summarised using the Kaplan–Meier estimator. A Cox regression model was fitted to explore variables that could theoretically be associated with resumption of prescription, based on the previous descriptive analysis. These included gender, referral to adult psychiatry, non-ADHD psychotropic primary care prescribing aged 18 and under or aged 19 and over, and recorded psychiatric comorbidities, as well as age at stopping medication. Each variable was initially examined in an unadjusted Cox regression model, reporting hazard ratios. Predictor variables with a
p value less than 0.05 were then included in a multivariable (adjusted) Cox regression model, with the same tests of the proportional hazards assumption applied. The proportional hazards assumption was checked by examining Schoenfeld residuals and plotting Nelson–Aalen cumulative hazard estimates. Statistical analyses were carried out using Stata software (version 14) [
23].
Findings
There were 1440 young people in the analysis who met our inclusion criteria. Of these, 1293 were male (89.8%), 395 (27.4%) had a prescription for a non-ADHD psychotropic medication at any point, 348 (24.2%) had a recorded diagnosis of another psychiatric disorder (excluding learning disability), and 64 (4.4%) had a recorded learning disability.
In our sample, 109 participants (7.6%, 95% CI 6.3–9.1%) had their prescriptions resumed at the age of 20 years or over. Of the 147 females in the sample, 17 (11.6%) resumed medication, compared to 92 of 1293 males (7.1%).
Ages of stopping and resuming medication
Of the 1440 participants, 427 (29.7%) stopped medication at age 16 years, which was the most common age for cessation, although 372 participants (25.8%) stopped medication at 17 years and 319 (22.2%) at 18 years.
Table
1 displays the percentage of young people in our sample whose prescriptions were resumed at specific ages. The majority of those who did restart did so before the age of 22 years.
Table 1Outcomes of young people who stopped ADHD prescriptions aged 14–18 years
Did not restart | 1331 | 92.4 |
Restarted age 20 | 66 | 4.6 |
Restarted age 21 | 19 | 1.3 |
Restarted age 22 | 15 | 1.0 |
Restarted age 23 | 6 | 0.4 |
Restarted age 24 | 2 | 0.1 |
Restarted age 25 | 1 | 0.1 |
Total | 1440 | 100 |
Once prescriptions were resumed, the median duration of persistence was 1 year (interquartile range 1–4 years) with the range from less than a year to 5 years; cases still prescribed medication at 6 years or more post-resumption were censored (see “
Methods”).
Overall, the later the young person stopped medication, the more likely they were to restart prescriptions in early adulthood. Only 6 (5.3%) of the 113 who stopped medication at age 14 years resumed medication, compared to 42 (13.2%) of the 319 who stopped medication aged 18 years (Table
2).
Table 2Resumption status by age of stopping ADHD prescription
Age 14 (N = 113) | 6 (5.3%) |
Age 15 (N = 209) | 5 (2.4%) |
Age 16 (N = 427) | 24 (5.6%) |
Age 17 (N = 372) | 32 (8.6%) |
Age 18 (N = 319) | 42 (13.2%) |
Resumption of primary care prescriptions for ADHD medication by characteristics
Table
3 describes the number and percentage of young people with different characteristics, whose ADHD prescriptions resumed in early adulthood. Resumption levels were highest amongst cases with a recorded referral to adult mental health services, those with a learning disability, and those prescribed a non-ADHD psychotropic medication (Table
3). In terms of psychiatric diagnoses, of the 35 cases in the sample with a substance misuse diagnosis, 6 resumed medication for their ADHD, compared to 9 of the 92 with conduct or oppositional defiant disorder.
Table 3Resumption of primary care prescriptions for ADHD medication by recorded characteristic
Prescription for non-ADHD psychotropic (N = 395) | 52 (13.2%) |
Referral recorded to adult mental health services (N = 142) | 28 (19.7%) |
Any non-ADHD psychiatric disorder (excluding learning disability) (N = 348) | 36 (10.3%) |
Conduct or oppositional defiant disorder (N = 92) | 9 (9.8%) |
Learning disability (N = 64) | 12 (18.8%) |
Autism spectrum disorder (N = 112) | 13 (11.6%) |
Anxiety or depression (n = 125) | 15 (12.0%) |
Substance misuse (N = 35) | 6 (17.1%) |
All cases (N = 1440) | 109 (7.6%) |
Time to resumption
The cumulative percentage of prescription resumption rose with age, but then remained stable from the age of 24 years; additionally, far fewer cases remained in the survival analysis after this point with a high proportion being censored. The estimated cumulative probability of resumption at 1 year (by age 20) was 4.6% (95% CI 3.5–5.8%); at 3 years (by the age of 22), this had risen to 7.6% (95% CI 6.3–9.2%) and at 5 years (by age 24) this was 9.7% (95% CI 7.7–12.0%).
Factors associated with resumption
The probability of resumption rose most steeply in the first 2 years of observation from age 20 years. When fitting the Cox regression model, there was evidence of violation of the proportional hazards assumption for some variables when examining resumption over the full follow-up period (see “
Methods”). Table
4 therefore presents the Cox regression model for the 3 year period when cases were aged 20–22 years, where the proportional hazards assumption was met.
Table 4Unadjusted and adjusted Cox regression model for resumption of prescription aged 20–22 years
Female gender | 1.91 (1.09–3.32) | 0.02 | 1.81 (1.04–3.26) | 0.05 |
Referral recorded to adult mental health services | 3.27 (2.01–5.31) | < 0.0001 | 2.18 (1.30–3.66) | 0.003 |
Learning disability | 3.64 (1.98–6.70) | < 0.0001 | 2.43 (1.25–4.74) | 0.009 |
Conduct disorder | 1.32 (0.61–2.86) | 0.48 | | |
Autism spectrum disorder | 1.99 (1.09–3.67) | 0.03 | 1.47 (0.76–2.83) | 0.26 |
Anxiety or depression | 1.57 (0.83–2.96) | 0.16 | | |
Substance misuse | 2.57 (1.04–6.33) | 0.04 | 1.81 (0.72–4.56) | 0.21 |
Antidepressant prescription aged 19 and over | 2.08 (1.28–3.41) | 0.004 | 1.08 (0.63–1.86) | 0.77 |
Antipsychotic prescription aged 19 and over | 6.93 (3.97–12.1) | < 0.0001 | 3.58 (1.86–6.88) | < 0.0001 |
Anxiolytic/hypnotic prescription aged 19 and over | 3.20 (1.60–6.39) | < 0.001 | 1.83 (0.88–3.80) | 0.10 |
Age at stopping medication (17 or 18 versus 14–16) | 2.25 (1.43–3.53) | < 0.0001 | 2.04 (1.28–3.24) | 0.003 |
In the adjusted model, female gender remained associated with an increased probability of resumption, as did a recorded referral to adult mental health services and having a recorded learning disability diagnosis. Prescription of antipsychotic medication was also strongly associated with resumption. Those that were older at the time of stopping medication also appeared to be more likely to restart within this time period.
Comparison of non-ADHD psychotropic prescribing in individuals who did and did not resume ADHD prescriptions
As shown in Table
5, prescribing of all categories of non-ADHD psychotropic medication was more common in young people resuming prescriptions. Almost half of those who resumed ADHD prescriptions also had a primary care prescription for a non-ADHD psychotropic medication. Prescription of different categories of non-ADHD psychotropics (e.g., an antidepressant and an antipsychotic) was also more common in those with prescription resumption.
Table 5Comparison of non-ADHD psychotropic prescribing in individuals who did and did not resume ADHD prescriptions
Any non-ADHD psychotropic prescription, n (%) | 343 (25.8%) | 52 (47.7%) | < 0.0001 |
Antidepressant prescription, n (%) | 228 (17.1%) | 36 (33.0%) | < 0.0001 |
Antipsychotic prescription, n (%) | 136 (10.2%) | 22 (20.2%) | 0.001 |
Anxiolytic/hypnotic prescription, n (%) | 69 (5.2%) | 13 (11.9%) | 0.003 |
Multiple prescribing (more than one category of non-ADHD psychotropic), n (%) | 79 (5.9%) | 16 (14.7%) | < 0.0001 |
Conclusion
This study suggests that most of those who stop medication in adolescence do not have their prescriptions resumed in early adulthood. Those that could benefit from resuming their medication as adults need to be able to do so in a safe and stable manner in order to experience improved outcomes. Our findings raise questions around whether current models of care and prescribing are suitable and flexible enough for young adults with ADHD, and whether professionals in primary care are adequately supported by specialist services in managing this group. As a result, there is a need for studies to examine the barriers to implementation of guidance, and for evaluation to develop and refine feasible and acceptable models within an environment of resources constraints.
Acknowledgements
This research was funded as part of a Doctoral Research Fellowship from the National Institute for Health Research held by Tamsin Newlove-Delgado (Reference: DRF-2012-05-221). Tamsin Newlove-Delgado is currently funded by an NIHR Academic Clinical Lectureship. Ken Stein and Obioha C. Ukoumunne were funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula at Royal Devon and Exeter NHS Foundation Trust. This report is independent research and the views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care.
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