17 May 2021

Farahbakhshian S et al. CNS Drugs 2021; Epub ahead of print

This retrospective study aimed to enhance knowledge of healthcare gaps in young adults diagnosed with ADHD with and without psychiatric comorbidities by characterising pharmacotherapy treatment patterns and healthcare resource utilisation (HRU) in individuals with ADHD during the transition period from adolescence (aged 16 years) to early adulthood (aged 21 years).

A retrospective claims analysis was conducted of the IBM® MarketScan® Commercial Databases, which represent all census regions of the USA, between 1 January 2008 and 31 December 2017, and includes claims data for medical and pharmacy services. Individuals with ≥2 claims related to ADHD diagnoses (≥1 claim related to diagnoses while aged 17) who were prescribed ADHD medication for ≥6 months at age 17 years were included. Continuous enrolment from age 16–21 years ensured that complete information on each individual was obtained. Pharmacotherapy use was evaluated by examining treatment discontinuation, switching, augmentation and sequencing.* Discontinuation, switching and augmentation were evaluated among individuals using ADHD pharmacotherapy as of their 18th birthday. Evaluations of HRU included all-cause inpatient visits, all-cause emergency department (ED) visits and outpatient visits.

In total, data from 10,292 individuals (64% male; 60.2% had a comorbid psychiatric disorder) met study entry criteria. The most frequently reported co-occurring psychiatric disorders (affecting >5% of individuals) were anxiety disorders (17.5%), trauma- and stressor-related disorders (14.9%), depressive disorders (12.5%), neurodevelopmental disorders (7.3%), disruptive, impulse control and conduct disorders (6.6%), and bipolar and related disorders (5.7%).

Treatment use

The overall proportion of individuals receiving any ADHD pharmacotherapy, long-acting stimulant therapy, short-acting stimulant therapy, or non-stimulant therapy significantly decreased, regardless of treatment type and presence of co-occurring psychiatric disorders, as individuals aged (p<0.001). Significantly more individuals with co-occurring psychiatric disorders used lisdexamfetamine, dextroamphetamine–amfetamine mix short-acting, and non-stimulants, compared with individuals without co-occurring psychiatric disorders, across all age groups (p<0.05).

Treatment discontinuation

The median time to treatment discontinuation was 2.94 years (95% confidence interval [CI] 2.86–3.03) when defined as a treatment lapse of >60 days and 3.78 years (95% CI 3.69–3.85) when defined as a treatment lapse of >90 days. The median (95% CI) time to treatment discontinuation was longer for individuals with ADHD with co-occurring psychiatric disorders versus those without, with treatment lapses of both >60 days (3.12 [3.00–3.21] vs 2.72 [2.59–2.83] years) and >90 days (3.89 [3.76–4.01] vs 3.64 [3.52–3.78] years).

Treatment switching and augmentation

Among individuals using pharmacotherapy at the age of 17 years (n=8424), 22.5% switched treatment within 60 days before or after the discontinuation of index treatment after 3 years. A higher percentage of individuals with co-occurring psychiatric disorders (n=5106) versus without (n=3318) switched treatment after 1 (12.7% vs 8.5%), 2 (19.2% vs 15.6%) and 3 years (24.4% vs 19.6%). Among individuals using pharmacotherapy at the age of 17 years and persisting with that treatment for ≥60 days (n=6802), more than 31.3% were using an augmentation strategy after 3 years. A greater proportion of individuals with co-occurring psychiatric disorders (n=4095) versus without (n=2707) used an augmentation strategy after 1 (21.0% vs 10.0%), 2 (31.3% vs 17.2%) and 3 years (38.5% vs 19.8%).

Treatment sequence

Starting and remaining on long-acting amfetamines or long-acting methylphenidates was the most frequently observed treatment sequence. As individuals aged, there were decreases in the proportion using long-acting amfetamines (18 years, 31.2%; 19 years, 23.1%; 20 years, 20.3%; 21 years, 17.8%) and long-acting methylphenidates (18 years, 17.7%; 19 years, 12.0%; 20 years, 9.5%; 21 years, 7.8%). Similarly, there were decreases with age in the proportion of individuals using non-stimulants (17 years, 10.0%; 18 years, 7.2%; 19 years, 5.2%; 20 years, 4.5%; 21 years, 4.3%) or mixed therapy (17 years, 8.4%; 18 years, 4.1%; 19 years, 3.5%; 20 years, 2.8%; 21 years, 2.3%). The proportion receiving no treatment increased with age (18 years, 9.4%; 19 years, 25.8%; 20 years, 35.7%; 21 years, 42.8%) alongside those with disrupted treatment (18 years, 24.1%; 19 years, 23.8%; 20 years, 20.2%; 21 years, 17.9%). After transitioning to disrupted treatment or no treatment, low percentages of individuals returned to pharmacotherapy use (disrupted treatment: 15.7–21.5% per year; no treatment, 2.7–3.8% per year).

Healthcare resource utilization

All-cause inpatient and outpatient visits significantly decreased with age (16–17 years, 7.5% and 100%; 18–19 years, 6.5% and 99.2%; 20–21 years, 7.3% and 95.4%, respectively [p<0.05]), while primary care physician visits increased (53.0% for 16–17 years vs 61.0% for 18–19 years [p<0.05] and 61.8% for 20–21 years [p<0.05]). The percentage of individuals having ≥1 all-cause inpatient, ED or outpatient visit was significantly greater for individuals with co-occurring psychiatric disorders across all ages (p<0.05).

Limitations of this study include that causal relationships in these data cannot be inferred due to the retrospective, observational methodology of the study and that treatment patterns may not reflect the physicians’ intent, as they were defined using prespecified algorithms. Additionally, the reasons for changes in treatment patterns were unavailable; some discontinuations of treatment were likely due to a loss of insurance coverage or perceived resolution of ADHD symptoms. Furthermore, the results of this study are only applicable to commercially insured US populations and are limited in their generalisability due to the requirement that individuals remain on their parent’s insurance beyond the age of 18 years.

In conclusion, in this study, the percentage of individuals using ADHD pharmacotherapy decreased during the transition from adolescence to early adulthood and the proportion experiencing treatment disruptions or discontinuations increased with age. Individuals rarely reinitiated treatment after pharmacotherapy was disrupted or discontinued, which the authors suggested emphasises the need for increased focus on the management of ADHD as individuals transition from adolescence to adulthood.

Read more about the effects of pharmacotherapy disruption during the transition from adolescence to adulthood in individuals with ADHD here

*Treatment discontinuation was defined as a lapse of >60 or >90 days between the end of medication supply (date of discontinuation) and the next prescription refill for any ADHD medication; treatment switching was defined as the initiation of a new ADHD medication not part of the index treatment (the treatment or combination of treatments used as from the individual’s 18th birthday) within 60 days before or after discontinuation of index treatment; treatment augmentation was defined as the initiation of a new ADHD or relevant medication not part of the index treatment before the discontinuation of index treatment, among individuals who persisted on the index treatment for ≥60 days.

Farahbakhshian S, Ayyagari R, Barczak DS, et al. Disruption of pharmacotherapy during the transition from adolescence to early adulthood in patients with attention-deficit/hyperactivity disorder: a claims database analysis across the USA. CNS Drugs 2021; Epub ahead of print.

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