title: Long-term (1 year) safety and efficacy of methylphenidate modified-release long-acting formulation (MPH-LA) in adults with attention-deficit hyperactivity disorder: a 26-week, flexible-dose, open-label extension to a 40-week, double-blind, randomised, placebo-controlled core study.
abstract: BACKGROUND
  Previously, in a 40-week, randomised, double-blind, placebo-controlled core study comprising three phases (9-week dose confirmation, 5-week open-label dose optimisation and 6-month maintenance of effect) in adults with attention-deficit/hyperactivity disorder (ADHD), methylphenidate modified-release long-acting formulation (MPH-LA) at 40-80 mg/day controlled ADHD symptoms as well as decreased functional impairment with a good tolerability profile (NCT01259492). Here, we report the long-term efficacy and safety from a 26-week, open-label extension phase of the same study (NCT01338818).
  
  
  METHODS
  Patients in the extension study (n = 298) initiated treatment with MPH-LA (20 mg/day), up-titrated in increments of 20 mg/week to reach individual patient's daily optimal dose of 40-80 mg. Adverse events (AEs) and serious adverse events (SAEs) were reported at the end of extension study for events monitored from (1) maintenance of effect phase baseline (core study; 12 months) and (2) extension study baseline (6 months). Mean changes in DSM-IV ADHD Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores are reported for both the timelines. Efficacy was also evaluated using clinician-rated instruments, namely Clinical Global Impression-Improvement Scale (CGI-I) and Clinical Global Impression-Severity Scale (CGI-S).
  
  
  RESULTS
  No unexpected AEs were reported in the extension study. Incidence of SAEs reported during 6 months and 12 months were similar (0.7 %), and no deaths were reported. No SAEs were considered attributable to the drug at the end of 12 months. There were no reports of patients with QT, QTcB or QTcF >500 ms. The mean improvement in DSM-IV ADHD RS and SDS total scores at the end of 12 months were 0.9 and 1.4 points, respectively; and at the end of 6 months were 7.2 and 4.8, respectively. The proportion of patients with improvement in CGI-S scale was 31.4 % and 52.1 % at the end of 12 and 6 months, respectively. Overall, 69.4 % of patients showed clinical improvement in CGI-I scale at the end of 6 months.
  
  
  CONCLUSIONS
  In adult patients with ADHD, use of MPH-LA up to 1 year continued to be well tolerated while maintaining the clinical efficacy.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Y
authors.initials: Y
authors.lastname: Ginsberg
authors.forename: T
authors.initials: T
authors.lastname: Arngrim
authors.forename: A
authors.initials: A
authors.lastname: Philipsen
authors.forename: P
authors.initials: P
authors.lastname: Gandhi
authors.forename: C-W
authors.initials: CW
authors.lastname: Chen
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.forename: M
authors.initials: M
authors.lastname: Huss
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D011619:Psychotropic Drugs; D008774:Methylphenidate