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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
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Patricia Murphy, MPH; Nikhil Khandelwal, PhD; and Ian Duncan, FSA, MAAA
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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.
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).

Patients with index amphetamines received augmentation mainly with other amphetamine formulations (141/173 patients augmented MAS XR with a generic AMPH salt combination). Similarly, most patients augmenting index OROS-MPH therapy did so with other MPH formulations (30/33 patients).

Cost Analyses

Medication Costs. Pharmacy costs per prescription fill at the drug level ranged from $119 for index LDX to $182 for index ATX. Pharmacy costs per prescription for the other medications were $141 for MAS XR and $139 for OROS-MPH (see Appendix).

Mean costs for nonindex ADHD medications (ie, those to which patients were switched or those that were used to augment index therapy) ranged from $38 for patients taking index MAS XR to $100 for those taking LDX. Median cost for nonindex ADHD medications was 0 for all index drug cohorts because fewer than half the patients in each group augmented therapy.

Overall, the mean ADHD-related pharmacy cost during the 6-month follow-up period was $518 (median cost, $460). Patients taking index ATX had the highest mean ADHD-related pharmacy costs ($557), followed by those taking MAS XR ($542), LDX ($536), and OROS-MPH ($436) (Table 2).

DACON and Pharmacy Costs. Total mean pharmacy costs were lower for patients with DACON of 1 pill compared with those with DACON of more than 1 pill. The median ADHD-related total pharmacy costs for patients with DACON of 1 pill were significantly lower than the costs for those with DACON of more than 1 pill in the follow-up period (P <.0001 for all medications; Figure 3). Incremental costs for patients with DACON of more than 1 pill (calculated as the absolute difference in median costs or as a proportion of the mean costs of DACON of 1 pill) were lowest for LDX patients ($234, 61%), followed by OROS-MPH ($241, 80%), ATX ($310, 88%), and MAS XR ($342, 96%) patients.

Augmentation and Pharmacy Costs. Total mean ADHD-related pharmacy costs were higher for all index medications with augmentation than without augmentation (Table 2). Median costs were significantly higher for patients who augmented their index medication than for patients who did not (P <.05 for all medications). The difference in median costs between those who augmented and those who did not was smallest for LDX ($603 vs $543, difference $60; P = .0391; increment 23%) and largest for ATX ($983 vs $467, difference $516; P = .0046; increment 141%) (Table 2).


As pharmacotherapy is currently the mainstay treatment for ADHD,4 increased diagnosis rates will likely result in an increase in total spending on drug and nondrug therapies. The impact on pharmacy budgets in the United States from the increased unit costs of newer ER agents likely will be partly offset by the provision of these agents at higher copay levels than IR formulations. However, payers may be under increased pressure to approve the least costly treatments available that offer the best quality of care for patients. It is important to consider outcome measures in addition to the variety of cost measures. For example, augmentation of the index medication may cause an incremental increase to a pharmacy budget, but overall treatment outcomes may be improved, with lower overall healthcare costs.9-11

Our study population, with a mean patient age of 30.0 years, had a virtually equal male-female distribution (1:1), whereas in a recent community-based study higher male prevalence was noted.12 However, the prevalence of diagnosed ADHD among adult females may be on the increase, as a shift in the ratio of females to males, increasing from 0.55 to 0.76 over a period of 5 years, was noted.13 It is possible that this shift reflects the increasing recognition that ADHD is equally likely to affect females and males, although historically it has been more commonly recognized in males, particularly children.

In our study, LDX was associated with relatively high pharmacy costs during the follow-up, partly due to the long(er) persistence (mean persistence, 116.5 days) compared with the other long-acting drug classes evaluated (mean persistence, 74.9-115.4 days). Further, LDX users also had the highest number of prescription fills, resulting in the lowest mean per prescription costs of the longacting medications evaluated.

Our results indicate that once-daily dosing was not always achieved. Most patients achieved DACON of 1 pill and did not require augmentation, but a sizable minority had DACON of more than 1 pill (~1 in 4) or required augmentation (~1 in 12). Patients taking index ATX had the highest mean DACON (1.32 pills), which is not surprising given that ATX can be prescribed for either onceor twice-daily dosing. For all 4 long-acting medications, higher DACON values were associated with higher pharmacy costs, likely due to the increased pill burden. The increase in ADHD-related pharmacy costs from DACON of 1 pill to DACON of more than 1 pill was lowest among index LDX users and highest among those taking MAS XR. The mean per prescription cost of LDX ($119) was lower than that for the other medications, which may explain why LDX had the lowest cost increase associated with DACON of more than 1 pill. However, even for LDX, the cost increment associated with DACON values above 1 was large when expressed in absolute terms or as a proportion of the mean cost associated with DACON of 1 pill, confirming the importance of DACON calculations in determining the total impact of long-acting ADHD medications on pharmacy budgets.

Augmentation was higher among stimulant users than among ATX users. As previously reported,14-16 augmentation with 1 or more ADHD medications during follow-up was associated with higher median ADHD pharmacy costs for the entire follow-up period, regardless of index medication. The incremental cost of augmentation was highest for ATX and lowest for LDX. For LDX, augmentation only added $60 (23%) to median treatment costs, despite LDX having the lowest pharmacy cost per prescription brand, which meant that the augmenting medications may have been more expensive than LDX. In contrast, augmentation added more than 50% to the pharmacy costs for subjects with index MAS XR and OROS-MPH, and more than doubled the costs for subjects with index ATX. For LDX, MAS XR, and OROS-MPH, the cost increments were lower for augmentation than for increased DACON, although the increments associated with augmentation were still considerable.

The mean cost of nonindex ADHD medications was higher for LDX patients ($100) than for other long-acting ADHD medications (the drugs commercially available for augmentation/switching may have been more expensive than LDX). However, fewer than half of patients in each group augmented therapy, so median costs for nonindex ADHD medications were 0 for all drugs. Notably, the mean costs of ADHD medications were higher in our study compared with the costs reported, with differences attributed to methodology and patient population (6-month mean ADHD drug cost was $282 for OROS-MPH, $322 for MAS XR, and $392 for ATX).17


The data were derived from pharmacy claims data collected for payment and not for research. A filled prescription neither guaranteed that medication was consumed nor that it was taken as prescribed. No correction was made for length of prescription, and it is possible that prescription duration may have differed by drug; however, since the stimulants are controlled drugs and typically dispensed with a 30-day prescription, the impact of this possibility was considered limited. Although the number of prescriptions filled and the days of index medication supplied were recorded, the numbers of patients who filled multiple prescriptions for the index medication on a given day and who had multiple fills on the index date were not measured.

This study aimed to evaluate medication utilization among newly treated patients. On this basis, 19.7% of patients were excluded because of prior/ongoing treatment in the 6-month preindex period.

The numbers of patients receiving transdermal MPH or d-MPH XR was small (<5% of total population); hence, they were excluded from drug-specific analyses (but did contribute to overall analysis population). There were higher proportions of males in the OROS-MPH and ATX groups, which may have confounded comparisons with other groups; this is particularly relevant for patients receiving OROS-MPH, as responses to this medication have been reported to differ between male and female children.18

Diagnostic code requirements for ADHD as well as a prescription for an ADHD medication reduced the likelihood that a patient without ADHD would be incorrectly included. While a 6-month period with no prior ADHD medications was required for study entry, this did not guarantee that all patients were newly treated, as those on an extended “drug holiday” could have also fulfilled the inclusion criteria.

Finally, this study did not consider generic drugs. At present, the only long-acting drug formulation for the treatment of ADHD that has a generic equivalent is MAS XR. This generic form was introduced in the market in April 2009, after our data set was obtained and analyzed; therefore, no information on generic drugs could be obtained from our data.


Managing a pharmacy budget requires comprehensive evaluation of treatment outcomes and various costs. Several factors affect the total pharmacy costs: the cost of all index medication prescriptions filled (a product of the per prescription cost and the number of prescriptions filled) and the cost of all nonindex medications filled for augmentation. In our study population, LDX users had lower DACON and longer persistence on the index drug, and were less likely to augment the index treatment, resulting in higher index and total drug costs. Thus, it is recommended that pharmacy managers consider the benefits of persistence on therapy as well as the costs associated with higher DACON and augmentation when choosing ADHD drug treatment.

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