title: Long-term treatment outcomes with lisdexamfetamine dimesylate for adults with attention-deficit/hyperactivity disorder stratified by baseline severity.
abstract: OBJECTIVE
  To examine the impact of baseline severity on lisdexamfetamine dimesylate (LDX) efficacy in a long-term study of adults with attention-deficit/hyperactivity disorder (ADHD).
  
  
  METHODS
  Adults from a 4-week, placebo-controlled, forced dose-escalation study with LDX (30-70 mg/day) or placebo were enrolled in a long-term, open-label dose-optimization study for an additional 12 months. In post hoc analyses, participants were stratified by baseline severity (from the prior short-term study) with Clinical Global Impressions-Severity (CGI-S) scores of 4 (moderately), 5 (markedly), or ≥6 (severely/extremely ill). ADHD-Rating Scale IV (ADHD-RS-IV) with adult prompts (primary) and CGI-Improvement (CGI-I) were used to assess effectiveness. Clinical response was defined as a ≥30% decrease in ADHD-RS-IV from baseline and a CGI-I of 1 or 2; symptomatic remission was defined as ADHD-RS-IV ≤18. Treatment-emergent adverse events (TEAEs) were monitored.
  
  
  RESULTS
  Participants had baseline CGI-S scores of 4 (n = 114), 5 (n = 188), or ≥6 (n = 43). At endpoint, mean (SD) change from baseline in ADHD-RS-IV was greater (p < 0.0001) for participants with CGI-S = 5 (-26.4 [11.77]) and ≥6 (-32.3 [9.81]) than for participants with CGI-S = 4 (-19.5 [9.97]). At endpoint, 81.6%, 84.6%, and 88.4% of participants were very much/much improved (CGI-I of 1 or 2) in CGI-S categories of 4, 5, and ≥6, respectively. Clinical response criteria were met by 78.9%, 83.5%, and 88.4% and symptomatic remission criteria by 64.0%, 65.4%, and 72.1% of participants with CGI-S = 4, 5, and ≥6, respectively. The most frequently reported TEAEs with participant incidence ≥10% for any LDX dose were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%).
  
  
  CONCLUSIONS
  Some aspects of these analyses (e.g., open-label design without placebo control, inclusion and exclusion criteria of the demographic profile of participants, and the post hoc nature of the statistical analysis) limit interpretation. However, long-term LDX treatment demonstrated increased degree of symptom improvement with greater baseline symptom severity. Rates of clinical response and symptomatic remission tended to be greater for those with greater baseline severity. LDX demonstrated a safety profile consistent with long-acting stimulant use.
authors: Red Oak Psychiatry Associates, PA, Houston, TX 77090, USA. larrydg@earthlink.net
authors: Lawrence
authors: L
authors: Ginsberg
authors: Alain
authors: A
authors: Katic
authors: Ben
authors: B
authors: Adeyi
authors: Bryan
authors: B
authors: Dirks
authors: Thomas
authors: T
authors: Babcock
authors: Robert
authors: R
authors: Lasser
authors: Brian
authors: B
authors: Scheckner
authors: Lenard A
authors: LA
authors: Adler
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D003913:Dextroamphetamine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine