Impact of atypical antipsychotic use among adolescents with attention-deficit/hyperactivity disorder

Objectives To compare treatment patterns, resource utilization, and costs to US third-party payers of stimulant-treated adolescent attentiondeficit/ hyperactivity disorder (ADHD) patients who switched to or augmented with atypical antipsychotics (AAPs; not FDA-indicated for ADHD) with those who switched to or augmented with nonantipsychotic medications.

Study Design Retrospective cohort study conducted using a US commercial medical/pharmacy claims database.

Methods Adolescent patients with an ADHD diagnosis and ≥1 stimulant medication claim between January 2005 and December 2009 were identified. Patients were classified into the AAP or non-antipsychotic cohorts based on subsequent claims for AAPs or nonantipsychotic medications, respectively. Patients with psychiatric diagnoses for which AAPs are often prescribed were excluded. Patients were matched 1:1 from the AAP to the non-antipsychotic cohort using propensity score matching. Treatment patterns, resource utilization, and costs in the 12 months after AAP or non-antipsychotic initiation were compared using Cox models, Poisson regression, and Wilcoxon signedrank tests, respectively.

Conclusions Stimulant-treated adolescents with ADHD who switched to or augmented with AAPs had significantly greater drug augmentation, healthcare resource utilization, and costs compared with the non-antipsychotic cohort. Atypical antipsychotics (AAPs) are one of the most common and costly classes of prescription drugs, with annual expenditures exceeding $13 billion, representing nearly 5% of all drug expenditures in the US.1,2 AAPs are approved by the FDA for the treatment of schizophrenia, behavioral symptoms in autism, and mixed or manic bipolar disorder, and the benefits and risks of AAPs are well documented for these indications.3 However, AAP use for off-label indications has rapidly increased, and now accounts for the majority of AAP utilization.4,5 A recent study found that AAP use in children grew by 62% from 2002 to 2007.6 Due to the potential side effects of AAP use and limited clinical evidence regarding the efficacy and safety of such off-label uses, the utilization of atypical antipsychotics for off-label indications is controversial.5,7,9 Among studies of off-label AAP use, heightened attention has been paid to attention-deficit/hyperactivity disorder (ADHD), as almost a third of offlabel AAP use is related to this condition.7-9. ADHD can pose a significant barrier to personal development and cause substantial psychological difficulties for patients and their families if left untreated.10 There are many pharmacologic treatment options for ADHD, including stimulants and non-stimulants, which have well-established efficacy and safety profiles.11 Conversely, the risks and benefits of AAP use in current clinical practice for ADHD are largely unknown.12 The few clinical studies that investigated AAP use in ADHD patients are confounded by patient comorbidities for which AAPs may be appropriate, and are therefore difficult to interpret.13-16 However, the pediatric population appears to be at higher risk than adults for AAPinduced adverse events including weight gain, elevation in prolactin levels, extrapyramidal symptoms, sedation, and cardiac events.1,8,19 Additionally, there is limited evidence regarding the real-world economic outcomes of AAP use for ADHD, and recent literature has called for further investigation of the health outcomes in pediatric populations.6 A companion study examined this effect in children aged 6 to 12 years with ADHD, finding that patients who utilized AAPs had higher rates of drug switching and augmentation, greater medical resource utilization, and higher total healthcare costs compared with patients who used nonantipsychotic therapies.20 However, no peer-reviewed publications have investigated the economic costs of AAP use specifically in adolescents with ADHD. There is evidence that both the rates of ADHD diagnosis and AAP prescription for ADHD can vary by age category, which indicates the need for specific attention to the adolescent subpopulation.5,7,9,21. Therefore, the purpose of this study was to compare, from a US third-party payer perspective, treatment patterns, resource utilization, and healthcare costs of stimulanttreated adolescents with ADHD who switched to or augmented their stimulant treatment with AAPs, versus those who did the same with non-antipsychotic medications.

Results After propensity score matching, a total of 849 adolescents were included in each of the matched cohorts. Patients in the AAP cohort had a significantly higher rate of medication augmentation (27.7% vs 15.5%; hazard ratio = 2.56; 95% confidence interval [CI], 1.90-3.46; P <.001) than patients in the non-antipsychotic cohort. The AAP cohort also had significantly higher incidences of inpatient admissions (0.13 vs 0.05; incidence rate ratio [IRR] = 2.45; 95% CI, 1.73-3.48; P <.001), emergency department visits (0.39 vs 0.31; IRR = 1.27; 95% CI, 1.08-1.49; P = .004), and outpatient visits (14.82 vs 13.19; IRR = 1.12; 95% CI, 1.10-1.15; P <.001), and incurred significantly higher mean annual medical ($3622 vs $3311; P = .002), drug ($4314 vs $2884; P <.001), and total healthcare ($7936 vs $6195; P <.001) costs.