title: Impact of stimulant pharmacotherapy on sleep quality: post hoc analyses of 2 large, double-blind, randomized, placebo-controlled trials.
abstract: BACKGROUND
  Sleep disturbances may cause distress among individuals with attention-deficit/hyperactivity disorder (ADHD), but few studies have examined the impact of stimulant pharmacotherapy for ADHD on sleep in adults.
  
  
  METHODS
  These post hoc analyses included sleep data collected with the Pittsburgh Sleep Quality Index (PSQI), a self-rated questionnaire, from 831 adults with DSM-IV-TR-defined ADHD in 2 large, randomized, double-blind, placebo-controlled, forced-dose titration studies of lisdexamfetamine (N = 420; conducted from May 25, 2006, to November 16, 2006) and triple-bead mixed amphetamine salts (MAS) (N = 411; conducted from April 25, 2005, to November 4, 2005). Change from baseline to endpoint in PSQI clinically meaningful change categories (ie, "decrease," "no change," or "increase") was analyzed by treatment group in each study using the χ² test. The Cochran-Mantel-Haenszel method was used (1) to determine whether there was a statistically significant difference in Clinical Global Impressions-Improvement (CGI-I) score of 1 or 2 (improved) versus > 2 (not improved) relative to a decrease or an increase in PSQI and (2) to analyze shifts from good sleep at baseline (PSQI ≤ 5) to poor sleep at endpoint (PSQI > 5).
  
  
  RESULTS
  Impaired sleep (PSQI score > 5) relative to baseline was demonstrated in 8.3% and 9.7% of the treatment and placebo groups, respectively (P = .18), in the MAS study and 7.7% and 8.2%, respectively (P = .03), in the lisdexamfetamine study. Clinically meaningful change in baseline to endpoint PSQI was not statistically significantly different between treatment and placebo groups in either study. A significant difference in CGI-I 1 and 2 relative to an increase or decrease in PSQI was found in both the triple-bead MAS (P < .0001) and the lisdexamfetamine (P = .0008) trials. More subjects with improved CGI-I rating of 1 or 2 had improvement in PSQI than had worsening.
  
  
  CONCLUSIONS
  Approximately one-third of subjects receiving treatment or placebo had clinically meaningful sleep improvement, emphasizing that change in sleep quality during treatment may not necessarily be related to stimulant therapy. When managing complaints of sleep difficulties in ADHD subjects, clinicians should undertake a broad assessment and consider underlying conditions that may contribute to sleep disruption.
  
  
  BACKGROUND
  clinicaltrials.gov Identifiers: NCT00334880 and NCT00152022.
authors.affiliation: Clinical and Research Program in Adult ADHD, Massachusetts General Hospital, Ste 2000, 185 Alewife Brook Pkwy, Cambridge, MA 02138, USA. csurman@partners.org
authors.forename: Craig B H
authors.initials: CB
authors.lastname: Surman
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
mesh_terms: D000328:Adult; D000662:Amphetamines / Q000009:adverse effects* / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D003913:Dextroamphetamine / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D008875:Middle Aged; D012890:Sleep / Q000187:drug effects*; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced* / Q000175:diagnosis / Q000523:psychology; D011795:Surveys and Questionnaires
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine