Systematic review of quality of life and functional outcomes in randomized placebo-controlled studies of medications for attention-deficit/hyperactivity disorder

Abstract

Children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) experience functional impairment and poor health-related quality of life (HRQoL) in addition to symptoms of inattention/hyperactivity-impulsivity. To synthesize qualitatively the published evidence from randomized, double-blind, placebo-controlled trials of the effectiveness of pharmacotherapy on functional impairment or HRQoL in patients with ADHD, a systematic PubMed searching and screening strategy was designed to identify journal articles meeting pre-specified criteria. Post hoc analyses and meta-analyses were excluded. HRQoL outcomes, functional outcomes and the principal ADHD symptom-based outcome were extracted from included studies. An effect size of 0.5 versus placebo was used as a threshold for potential clinical relevance (unreported effect sizes were calculated when possible). Of 291 records screened, 35 articles describing 34 studies were included. HRQoL/functioning was usually self-rated in adults and proxy-rated in children/adolescents. Baseline data indicated substantial HRQoL deficits in children/adolescents. Placebo-adjusted effects of medication on ADHD symptoms, HRQoL and functioning, respectively, were statistically or nominally significant in 18/18, 10/12 and 7/9 studies in children/adolescents and 14/16, 9/11 and 9/10 studies in adults. Effect sizes were ≥0.5 versus placebo for symptoms, HRQoL and functioning, respectively, in 14/16, 7/9 and 4/8 studies in children/adolescents; and 6/12, 1/6 and 1/8 studies in adults. Effect sizes were typically larger for stimulants than for non-stimulants, for symptoms than for HRQoL/functioning, and for children/adolescents than for adults. The efficacy of ADHD medication extends beyond symptom control and may help reduce the related but distinct functional impairments and HRQoL deficits in patients with ADHD.

Keywords: Attention-deficit/hyperactivity disorder; Functional impairment; Quality of life; Randomized clinical trials; Systematic review.

Fig. 1

Effects of ADHD on a patient’s life extend beyond symptoms. ADHD attention-deficit/hyperactivity disorder

Fig. 2

PRISMA diagram. ^a35 articles describing 34 studies. Symptom-based outcome data for studies reported in eight included articles were extracted from an additional eight articles cited in the included articles. PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Fig. 3

Pre-treatment baseline CHIP-CE:PRF T-scores in children and adolescents with ADHD. T-scores have a mean of 50 and a standard deviation of 10. Circle diameter is proportional to T-score, with a diameter of zero corresponding to a T-score of 20. Rings indicate the mean in the reference population. ^aStudy SPD489-326 [15] (included in this review) involved mainly the same patients as the short-term LDX study SPD489-325 [14] (also included in this review), so only the former is shown. ^bPooled analysis of five ATX studies [43]: three randomized placebo-controlled trials (included in this review) [37, 42, 91], and two open-label studies (not included in this review). ^cObservational study (not included in this review), shown for comparison [80]. ^dObservational study with non-ADHD control groups (not included in this review), shown for comparison [32]. ADHD attention-deficit/hyperactivity disorder, ADORE Attention-Deficit/Hyperactivity Disorder Observational Research in Europe, ATX atomoxetine, CHIP-CE:PRF Child Health and Illness Profile-Child Edition: Parent Report Form, LDX lisdexamfetamine, T1DM type 1 diabetes mellitus