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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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).</p> <p>Results</p> <p>The mean baseline PSQI global score was 5.8 for LDX and 6.3 for placebo (<it>P </it>= .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 (<it>P </it>= .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, <it>P </it>= .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.</p> <p>Conclusion</p> <p>For most subjects, LDX was not associated with an overall worsening of sleep quality and significantly improved daytime functioning in adults with ADHD.</p> <p>Trial Registration</p> <p>clinicaltrials.gov Identifier: NCT00334880</p

Self-Reported quality of life in adults with attention-deficit/hyperactivity disorder and executive function impairment treated with lisdexamfetamine dimesylate: a randomized, double-blind, multicenter, placebo-controlled, parallel-group study

BackgroundThis study examined the effects of lisdexamfetamine dimesylate (LDX) on quality of life (QOL) in adults with attention-deficit/hyperactivity disorder (ADHD) and clinically significant executive function deficits (EFD).MethodsThis report highlights QOL findings from a 10-week randomized placebo-controlled trial of LDX (30–70 mg/d) in adults (18–55 years) with ADHD and EFD (Behavior Rating Inventory of EF-Adult, Global Executive Composite [BRIEF-A GEC] ≥65). The primary efficacy measure was the self-reported BRIEF-A; a key secondary measure was self-reported QOL on the Adult ADHD Impact Module (AIM-A). The clinician-completed ADHD Rating Scale version IV (ADHD-RS-IV) with adult prompts and Clinical Global Impressions-Severity (CGI-S) were also employed. The Adult ADHD QoL (AAQoL) was added while the study was in progress. A post hoc analysis examined the subgroup having evaluable results from both AIM-A and AAQoL.ResultsOf 161 randomized (placebo, 81; LDX, 80), 159 were included in the safety population. LDX improved AIM-A multi-item domain scores versus placebo; LS mean difference for Performance and Daily Functioning was 21.6 (ES, 0.93, P<.0001); Impact of Symptoms: Daily Interference was 14.9 (ES, 0.62, P<.0001); Impact of Symptoms: Bother/Concern was 13.5 (ES, 0.57, P=.0003); Relationships/Communication was 7.8 (ES, 0.31, P=.0302); Living With ADHD was 9.1 (ES, 0.79, P<.0001); and General Well-Being was 10.8 (ES, 0.70, P<.0001). AAQoL LS mean difference for total score was 21.0; for subscale: Life Productivity was 21.0; Psychological Health was 12.1; Life Outlook was 12.5; and Relationships was 7.3. In a post hoc analysis of participants with both AIM-A and AAQoL scores, AIM-A multi-item subgroup analysis scores numerically improved with LDX, with smaller difference for Impact of Symptoms: Daily Interference. The safety profile of LDX was consistent with amphetamine use in previous studies.ConclusionsOverall, adults with ADHD/EFD exhibited self-reported improvement on QOL, using the AIM-A and AAQoL scales in line with medium/large ES; these improvements were paralleled by improvements in EF and ADHD symptoms. The safety profile of LDX was similar to previous studies.Trial registrationClinicalTrials.gov, NCT0110102

Analysis of individual items on the attention-deficit/hyperactivity disorder symptom rating scale in children and adults: the effects of age and sex in pivotal trials of lisdexamfetamine dimesylate

Attention-deficit/hyperactivity disorder (ADHD) symptom presentation across age and sex has not been fully elucidated. The present post hoc analyses qualitatively explored the baseline levels of ADHD symptomatology across subgroups in two clinical trials of children and adults with ADHD to elucidate differences in participant presentation. The response to treatment was examined to determine patterns of response among items of the ADHD Rating Scale IV

Absence of Phase Transition for Antiferromagnetic Potts Models via the Dobrushin Uniqueness Theorem

We prove that the $q$-state Potts antiferromagnet on a lattice of maximum coordination number $r$ exhibits exponential decay of correlations uniformly at all temperatures (including zero temperature) whenever $q > 2r$. We also prove slightly better bounds for several two-dimensional lattices: square lattice (exponential decay for $q \ge 7$), triangular lattice ($q \ge 11$), hexagonal lattice ($q \ge 4$), and Kagom\'e lattice ($q \ge 6$). The proofs are based on the Dobrushin uniqueness theorem.Comment: 32 pages including 3 figures. Self-unpacking file containing the tex file, the needed macros (epsf.sty, indent.sty, subeqnarray.sty, and eqsection.sty) and the 3 ps file

Dynamic Critical Behavior of a Swendsen-Wang-Type Algorithm for the Ashkin-Teller Model

We study the dynamic critical behavior of a Swendsen-Wang-type algorithm for the Ashkin--Teller model. We find that the Li--Sokal bound on the autocorrelation time ($\tau_{{\rm int},{\cal E}} \ge {\rm const} \times C_H$) holds along the self-dual curve of the symmetric Ashkin--Teller model, and is almost but not quite sharp. The ratio $\tau_{{\rm int},{\cal E}} / C_H$ appears to tend to infinity either as a logarithm or as a small power ($0.05 \leq p \leq 0.12$). In an appendix we discuss the problem of extracting estimates of the exponential autocorrelation time.Comment: 59 pages including 3 figures, uuencoded g-compressed ps file. Postscript size = 799740 byte

Spanning forests and the q-state Potts model in the limit q \to 0

We study the q-state Potts model with nearest-neighbor coupling v=e^{\beta J}-1 in the limit q,v \to 0 with the ratio w = v/q held fixed. Combinatorially, this limit gives rise to the generating polynomial of spanning forests; physically, it provides information about the Potts-model phase diagram in the neighborhood of (q,v) = (0,0). We have studied this model on the square and triangular lattices, using a transfer-matrix approach at both real and complex values of w. For both lattices, we have computed the symbolic transfer matrices for cylindrical strips of widths 2 \le L \le 10, as well as the limiting curves of partition-function zeros in the complex w-plane. For real w, we find two distinct phases separated by a transition point w=w_0, where w_0 = -1/4 (resp. w_0 = -0.1753 \pm 0.0002) for the square (resp. triangular) lattice. For w > w_0 we find a non-critical disordered phase, while for w < w_0 our results are compatible with a massless Berker-Kadanoff phase with conformal charge c = -2 and leading thermal scaling dimension x_{T,1} = 2 (marginal operator). At w = w_0 we find a "first-order critical point": the first derivative of the free energy is discontinuous at w_0, while the correlation length diverges as w \downarrow w_0 (and is infinite at w = w_0). The critical behavior at w = w_0 seems to be the same for both lattices and it differs from that of the Berker-Kadanoff phase: our results suggest that the conformal charge is c = -1, the leading thermal scaling dimension is x_{T,1} = 0, and the critical exponents are \nu = 1/d = 1/2 and \alpha = 1.Comment: 131 pages (LaTeX2e). Includes tex file, three sty files, and 65 Postscript figures. Also included are Mathematica files forests_sq_2-9P.m and forests_tri_2-9P.m. Final journal versio