Effect of lisdexamfetamine dimesylate on sleep in adults with attention-deficit/hyperactivity disorder

Abstract

Background: Sleep problems are common in adults with attention-deficit/hyperactivity disorder (ADHD). This analysis aimed to evaluate the impact of lisdexamfetamine dimesylate (LDX) on sleep quality in adults with ADHD.

Methods: This 4-week, phase 3, double-blind, forced-dose escalation study of adults aged 18 to 55 years with ADHD randomized participants to receive placebo (n = 62), or 30 (n = 119), 50 (n = 117), or 70 (n = 122) mg/d LDX, taken once a day in the morning. The self-rated Pittsburgh Sleep Quality Index (PSQI) was administered at baseline and at week 4 to assess sleep quality. The PSQI global score assesses 7 sleep components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction) each scored from 0 (no difficulty) to 3 (severe difficulty).

Results: The mean baseline PSQI global score was 5.8 for LDX and 6.3 for placebo (P = .19) indicating poor overall sleep quality. At endpoint, least squares (LS) mean change from baseline was -0.8 for LDX vs -0.5 for placebo (P = .33). The daytime functioning component showed significant improvement in LS mean change at endpoint for LDX compared with placebo (LDX -0.4 vs placebo 0.0, P = .0001). LS mean changes for the other 6 PSQI components did not significantly differ from placebo. Sleep-related treatment-emergent adverse events with an incidence >/=2% in the active treatment and placebo groups, respectively, were insomnia (19.3% and 4.8%), initial insomnia (5.0% and 3.2%), middle insomnia (3.6% and 0%), sleep disorder (0.6% and 3.2%), somnolence (0.3% and 3.2%), and fatigue (4.7% and 4.8%), and were generally mild or moderate in severity.

Conclusion: For most subjects, LDX was not associated with an overall worsening of sleep quality and significantly improved daytime functioning in adults with ADHD.

Trial registration: clinicaltrials.gov Identifier: NCT00334880.

Figure 1

Subject disposition. (LDX = lisdexamfetamine dimesylate; AEs = adverse events).

Figure 2

Effect of LDX on global PSQI scores. Mean global PSQI scores of all treatment groups decreased from baseline indicating an improvement in sleep quality. Numbers within bars indicate numbers of subjects. (SD = standard deviation; SE = standard error; LS = least squares; PSQI = Pittsburgh Sleep Quality Index; LDX = lisdexamfetamine dimesylate).

Figure 3

Effect of LDX on daytime dysfunction (component 7) PSQI scores. Mean PSQI component 7 score (daytime dysfunction component) decreased significantly after treatment with LDX. Numbers within bars indicate numbers of subjects. (SD = standard deviation; SE = standard error; LS = least squares; PSQI = Pittsburgh Sleep Quality Index; LDX = lisdexamfetamine dimesylate). P-values for "all LDX doses" calculated by analysis of covariance with baseline score as covariate. P-values for individual LDX dose groups calculated by Dunnett's test for multiple mean comparisons with least-squares (LS) adjustment. * P < .01 vs placebo.

Figure 4

PSQI global scores for subjects reporting sleep-related TEAEs. PSQI scores are not worse at 4 weeks for subjects who reported sleep-related TEAEs. Numbers within bars indicate numbers of subjects. (TEAEs = treatment-emergent adverse events; PSQI = Pittsburgh Sleep Quality Index; LDX = lisdexamfetamine dimesylate; SD = standard deviation).