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Persistence, Augmentation, and Consumption of Long-Acting Medications in ADHD Patients
Paul Hodgkins, PhD, MSc; Rahul Sasané, PhD; Laura Christensen, MS; Haim Erder, PhD; and Carolyn Harley, PhD
Comparing Medication Wastage by Fill Quantity and Fulfillment Channel
Patricia Murphy, MPH; Nikhil Khandelwal, PhD; and Ian Duncan, FSA, MAAA
Wastage of Doses Higher With 90-Day Prescriptions
Jeffrey S. McCombs, PhD

Persistence, Augmentation, and Consumption of Long-Acting Medications in ADHD Patients

Paul Hodgkins, PhD, MSc; Rahul Sasané, PhD; Laura Christensen, MS; Haim Erder, PhD; and Carolyn Harley, PhD
Lisdexamfetamine dimesylate was associated with improved persistence compared with other classes of long-acting ADHD medications, which may lead to more efficient use of healthcare resources.
Objectives: To examine the relationship between pharmacy costs related to attention-deficit/hyperactivity disorder (ADHD) and persistence, daily average consumption (DACON), and augmentation in adults with ADHD.

Study Design: Retrospective analysis of pharmacy claims data from a commercial health plan between January 2007 and April 2008.

Methods: Costs were calculated as the sum of health plan and patient copayments for all ADHD medications; persistence as the total days patients remained on index therapy; and DACON as the quantity of medication supplied during the follow-up period divided by the total days of supply.

Results: In total, 2819 patients received long-acting ADHD medications (mixed amphetamine salts extended release [MAS XR], n = 1514; osmotic-release oral system methylphenidate [OROS-MPH], n = 546; atomoxetine [ATX], n = 513; lisdexamfetamine dimesylate [LDX], n = 246). Mean persistence was highest in LDX (116 days) and MAS XR (115 days) patients versus ATX (75 days) and OROS-MPH (83 days) patients. Higher DACON was associated with higher median cost for all medications (P <.0001 for each). Average costs were lowest for LDX. Overall, 235 patients (8.3%) augmented their index medication at an incremental burden of $60 (LDX), $244 (MAS XR), $232 (OROS-MPH), and $516 (ATX) added to median costs, equivalent to a 23% (LDX) to 141% (ATX) increase in acquisition costs.

Conclusions: LDX users had lower DACON and longer persistence, and were less likely to augment the index treatment resulting in higher index and total drug costs. Incremental cost associated with augmentation of index medication was lowest for LDX.

(Am J Pharm Benefits. 2012;4(6):e149-e158)
This study examined the relationship between pharmacy costs related to attention-deficit/hyperactivity disorder (ADHD) and utilization variables: daily average consumption (DACON), augmentation, and persistence.
  • Adult ADHD–related pharmacy costs were lowest for long-acting treatments and either associated with lower DACON or unaugmented with other ADHD medications.
  • Among the long-acting ADHD medications, lisdexamfetamine dimesylate had the highest persistence and lowest DACON, and the lowest incremental cost burden associated with treatment augmentation.
  • Payers managing pharmacy budgets for ADHD treatment should consider persistence on therapy, costs associated with DACON, and treatment augmentation, as well as direct acquisition costs.
Attention-deficit/hyperactivity disorder (ADHD), a neurobehavioral condition,1 affects approximately 4% of adults in the United States.2 Stimulants such as methylphenidate (MPH) and amphetamine form the mainstay of ADHD pharmacotherapy.3,4 Three nonstimulant drugs are currently approved for use in the United States (guanfacine extended-release [ER], clonidine ER, and atomoxetine [ATX]).

Persistence is a measure of the time a patient continues taking the initial medication; lack of effi cacy, tolerability issues, or difficulties with dosing compliance could cause persistence periods to end. Persistence among patients with mental health disorders is frequently suboptimal.5,6 However, data relating to treatment patterns for adults with ADHD are limited. One study indicated that adults persisted on therapy for a mean of 200 days, with the majority of patients persisting for less than 6 months.7 The study also found that 1.2% of adults augmented their index therapy with another stimulant, 11.1% switched to a new stimulant, and 53.7% required dose titration. In another study of adults with ADHD, only 50.5% of patients receiving immediate-release (IR) formulations of MPH and 61.4% of patients receiving ER formulations had more than 1 pharmacy claim for their index medication.8

Persistence and medication consumption patterns are appropriate metrics for comparing the utilization of medications. Daily average consumption (DACON) calculations are particularly relevant to healthcare payers because higher DACON values can be associated with increased medication costs and increased pharmacy budget. Although multitherapy approaches impact medication costs, the pattern of augmentation of an index medication can provide information on its real-world effectiveness.

The present study focused on the utilization of long-acting ADHD medications within a US-based managed care system. Specifically, the study compared persistence, DACON, and augmentation rates for different long-acting ADHD medications, and their relationships to total ADHD-related pharmacy costs.


This was a retrospective study of pharmacy claims data collected between January 2007 and April 2008. Costs included the amount paid by the insurance plan and the amounts paid by the patient.

Data Source

The claims data included medical and pharmacy claims, and eligibility information from a large, geographically diverse, national US health plan (>12 million enrollees with medical and pharmacy coverage). Medical claims included International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes, ICD-9-CM procedure codes, Current Procedural Terminology, version 4 procedure codes, Healthcare Common Procedure Coding System procedure codes, site of service codes, and health plan and patient costs. Outpatient pharmacy claims provided National Drug Codes for dispensed medications, quantity dispensed, drug strength, days of supply, and health plan and patient costs.

Patient Population

Adult patients with a preindex medical claim diagnosis of ADHD (ICD-9-CM diagnosis codes 314.00-314.9) and with 1 or more filled prescriptions for a long-acting ADHD treatment (index medication, including lisdexamfetamine dimesylate [LDX], mixed amphetamine salts extended release [MAS XR], osmotic-release oral system MPH [OROSMPH], dexmethylphenidate extended release [d-MPH XR], transdermal MPH, or ATX) between July 2007 and October 2007 were identified. Patients were aged 18 to 55 years at index date (date of earliest filled prescription), with continuous plan enrollment in pharmacy and medical benefits for 6 months prior to the index date (preindex period) and with pharmacy benefits for 6 months after the index date (follow-up period). Patients with prescription(s) for ADHD medications during the 6-month preindex period were excluded.


Outcomes were measured from the index date to the end of the follow-up period.

The number of prescriptions filled and the number of days of index medication supplied for the index medication were recorded. If the patient filled more than 1 prescription for the index medication on a given day, only 1 was counted in the calculation of persistence. If more than 1 prescription was filled on the index date, the prescription fill with the higher number of days of supply was used in calculations of days of supply. Counts of days supplied that were more than 183 were set to 183 (the duration of the follow-up period).

Persistence. Persistence was the total number of days the patient remained on index therapy. Patients were considered to have terminated therapy on the date of the last fill if the days of supply of that fill ran out more than 30 days prior to the end of the follow-up period. If the days of supply of the last fill ran out within 30 days of the end (or after the end) of the follow-up, persistence was set at 183 days.

DACON of the Index Medication. The DACON of the index medication was the quantity of medication supplied during the follow-up period divided by total number of days of supply. A DACON value of 1 indicated that a patient was dispensed 1 pill per day of the index medication. DACON values of more than 1 were indicative of a patient taking more than 1 pill daily. Mean DACON values and the proportion of patients with a DACON of 1 pill were recorded.

Augmentation. Augmentation was the filling of 1 or more prescriptions for any ADHD medication other than the index medication 30 days or more before the last prescription for the index medication was refilled. Thus, patients with a prescription fill for another ADHD medication before the last fill of the index medication were considered to have augmented the index therapy; those who switched ADHD medications (those with no prescription fills for the index medication after a prescription fill for another ADHD medication) were not captured in this definition. Augmentation medications were not limited to long-acting medications, and included MPH (IR or ER, or transdermal system), d-MPH (IR or XR), MAS (IR or XR), dextroamphetamine (IR or sustained release), LDX, and ATX. The proportion of patients augmenting their index medication, the number of augmentations dispensed, and the most frequently used augmentation medications were calculated.

Pharmacy costs during follow-up were calculated from the claims data as the sum of health plan costs and patient-paid amounts for all ADHD medications (index, augmentation, and total). ADHD-related pharmacy costs and incremental cost burdens were also calculated separately by DACON (additional costs by DACON level) and augmentation (additional costs associated with augmentation vs no augmentation).

Statistical Analysis

Study variables were analyzed descriptively. Numbers and percentages were recorded for dichotomous and polychotomous variables. Means, medians, and SDs were calculated for analyses of cost, days of supply, and count of prescription fills. Means and standard deviations (SDs) were calculated for analyses of continuous DACON values. Results were stratified by index medication. Proportions were compared using the X2 test, and means were compared using the t test. Distributions of costs were compared using the Mann-Whitney U test because of the skewed nature of these data. Additional statistics (minimum, maximum, 25th percentile, and 75th percentile) were calculated for persistence analyses, as the Mann-Whitney U test results were significant (indicating a difference in distributions) in some persistence analyses despite equal medians. To examine outcomes in those patients with longer persistence, additional analyses were undertaken for the subpopulation of patients with at least 90 days of supply of the index medication in the followup period. These included comparisons of the proportion of patients augmenting their index medication (using the X2 test) and of ADHD-related pharmaceutical costs during the follow-up period (using the Mann-Whitney U test). A P value of <.05 was considered statistically significant.



A total of 126,022 patients were identified with a claim for a long-acting index medication between July and October 2007. Of these, 30,835 met the age requirements and continuous enrollment requirements for the 6 months prior to and 6 months after the index date, and 2982 patients were considered newly treated ADHD subjects and met all inclusion criteria for the study.

The mean age of patients was 30.0 years (Table 1). Approximately half of the eligible patients were male (males, n = 1527, 51.2%; females, n = 1455, 48.8%) and approximately half (1514/2982, 50.8%) received index treatment with MAS XR, followed by OROS-MPH (n = 546; 18.3%), ATX (n = 513; 17.2%), and LDX (n = 246; 8.2%). The sample sizes for the transdermal MPH (n = 39) and d-MPH XR (n = 124) cohorts were too small to allow for meaningful comparisons among groups; hence, they were excluded from subsequent analyses by index medication but were included in statistics reflecting the entire study population.


The median length of time that patients continued their index therapy was 105 days (mean, 100.3 days). The median duration of persistence was longest for patients taking LDX (183 days; mean, 116.5 days) and MAS XR (183 days; mean, 115.4 days). The median duration of persistence was 36 days for ATX (mean, 74.9 days) and 58 for OROS-MPH (mean, 82.6 days). The Mann-Whitney U test revealed that longer persistence associated with DACON of more than 1 pill versus DACON of 1 pill was statistically significant for LDX (median 183 vs 183 days, respectively; mean 149.6 vs 111.7 days [P = .0213]) and MAS XR (median 183 vs 183 days, respectively; mean 129.6 vs 111.3 days [P = .0002]).

Of the 2819 patients, the number of prescriptions filled was highest for those receiving index therapy with LDX (4; mean, 3.66), followed by MAS XR (3; mean, 3.57), OROS-MPH (2; mean, 2.77), and ATX (2; mean, 2.58). The corresponding median numbers of days of supply of index medication were 113 for LDX (mean, 103.6), 91 for MAS XR (mean, 101.1), 60 for OROS-MPH (mean, 81.5), and 60 for ATX (mean, 79.8).

Daily Average Consumption. Of the 2819 patients, 2284 (81%) had a DACON of 1 pill; no patient had a DACON of less than 1 pill. Patients receiving index LDX had the lowest mean DACON (1.06 pills) and the largest proportion of patients with DACON of 1 pill (87.4%). Patients taking ATX had the highest mean DACON (1.32 pills) and the smallest proportion of patients with DACON of 1 pill (65.3%; Figure 1). Among the 698 patients with DACON of more than 1 pill, the mean (± SD) DACON was 1.45 (± 0.41) for LDX, 1.81 (± 0.57) for MAS-XR, 1.78 (± 0.51) for OROS-MPH, and 1.91 (± 0.44) for ATX.


Approximately 1 in 12 patients in the overall population augmented their index therapy (235/2819 patients, 8.3%). This proportion ranged from 1.4% for ATX to 11.4% for MAS XR; proportions for the other index medications were 6.0% (OROS-MPH) and 8.9% (LDX). A larger proportion of patients with DACON of more than 1 pill augmented their index therapy than those with DACON of 1 pill for all index medications, with this difference reaching statistical significance for MAS XR (15.7% of those with DACON >1 pill vs 10.2% of those with DACON = 1 pill; P = .0049; Figure 2).

Copyright AJMC 2006-2018 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
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