Efficacy and Safety of a Long-Acting Multilayer-Release Methylphenidate Formulation (PRC-063) in the Treatment of Adolescent Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Clinical Trial with a 6-Month Open-Label Extension

BackgroundData on the relationship between core symptoms and daily functioning in adults with attention deficit hyperactivity disorder (ADHD) are limited. Daily functioning was assessed as part of an open-label extension, and associations with symptom scores were evaluated.MethodAfter a 5-week double-blind study with adults with ADHD receiving osmotic-controlled release oral delivery system (OROS) methylphenidate (MPH) 18, 36 or 72 mg/day, or placebo, participants were eligible for a 7-week open-label extension in which all patients received OROS MPH. Data for the Conners' Adult ADHD Rating Scale – Observer: Screening Version (CAARS-O:SV) (primary endpoint) have been presented previously. Secondary endpoints included the observer self-reported short version of the CAARS (CAARS-S:S) and the Clinical Global Impressions – Severity Scale (CGI-S). Daily functioning and quality of life were assessed using the Sheehan Disability Scale (SDS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) respectively. In post-hoc analyses, changes in CAARS-O:SV were evaluated in subgroups. Relationships between symptom and functional outcomes were evaluated in a multivariate regression analysis.ResultsA total of 370 patients entered the open-label extension. Significant improvements from baseline in CAARS-O:SV were similar regardless of sex, ADHD subtype, prior treatment or psychiatric co-morbidity. Significant improvements from double-blind baseline were also seen for the CAARS-S:S, CGI-S, SDS and Q-LES-Q. Improvements in the CAARS-O:SV Hyperactivity/Impulsivity subscale were associated with improvements in SDS total and subscale scores, and in the Q-LES-Q score at open-label endpoint. Improvements in CAARS-O:SV Inattention subscale and CGI-S scores were not significantly associated with functional changes.ConclusionsImprovements in ADHD symptoms relating to hyperactivity and impulsivity in adults receiving OROS MPH are associated with improvements in daily functioning and quality of life.

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Methylphenidate treatment of adult male prison inmates with attention-deficit hyperactivity disorder: randomised double-blind placebo-controlled trial with open-label extension

The British Journal of Psychiatry ◽

10.1192/bjp.bp.111.092940 ◽

2012 ◽

Vol 200 (1) ◽

pp. 68-73 ◽

Cited By ~ 49

Author(s):

Ylva Ginsberg ◽

Nils Lindefors

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Adult Male ◽

Attention Deficit ◽

Prison Inmates ◽

Open Label ◽

Global Functioning ◽

Double Blind ◽

Double Blind Placebo ◽

Hyperactivity Disorder ◽

Open Label Extension

BackgroundAttention-deficit hyperactivity disorder (ADHD) is highly prevalent in prison inmates, but pharmacological treatment has not yet been evaluated in this group.AimsTo evaluate osmotic-release oral system (OROS) methylphenidate in adult male long-term prison inmates with ADHD.MethodRandomised, double-blind, placebo-controlled 5-week trial, followed by 47-week open-label extension in 30 prison inmates with ADHD and comorbid disorders. Primary outcome was level of ADHD symptoms after 5 weeks, evaluated by a masked assessor. Secondary outcomes were self-reported ADHD symptoms, global severity and global functioning throughout the 52-week trial, and post hoc treatment response and numbers needed to treat (NNT) (trial registration: NCT00482313.)ResultsTreatment significantly improved ADHD during the trial (P<0.001; Cohen's d = 2.17), with reduced symptom severity and improved global functioning. The placebo response, cardiovascular measures and adverse events were non-significant; the NNT was 1.1. Attention-deficit hyperactivity disorder symptoms, global severity and global functioning continued to improve during the open-label extension.ConclusionsOsmotic-release oral system methylphenidate is an effective treatment for adult male prison inmates with ADHD.

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Characteristics of ADHD Symptom Response/Remission in a Clinical Trial of Methylphenidate Extended Release

Journal of Clinical Medicine ◽

10.3390/jcm8040461 ◽

2019 ◽

Vol 8 (4) ◽

pp. 461 ◽

Cited By ~ 2

Author(s):

Margaret Weiss ◽

Ann Childress ◽

Earl Nordbrock ◽

Akwete Adjei ◽

Robert Kupper ◽

...

Keyword(s):

Clinical Trial ◽

Attention Deficit Hyperactivity Disorder ◽

Attention Deficit ◽

Extended Release ◽

Rating Scale ◽

Phase Iii ◽

Open Label ◽

Double Blind ◽

Hyperactivity Disorder ◽

Percent Change

Clinical trials in attention-deficit/hyperactivity disorder (ADHD) have typically measured outcome using clinician ratings on the Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Remission has been defined as an endpoint score of less than or equal to 18 on the ADHD-RS-IV (or a mean score of 1). Responders have been defined as patients who achieve a CGI-I score of much or very much improved (1 or 2). There is a lack of agreement in the literature on what percent change in symptoms on the ADHD-RS-IV should be used to define improvement or remission. This study uses data from a clinical trial of a methylphenidate extended release (MPH-MLR; Aptensio XR®) phase III clinical trial to attempt to determine the percent change of symptoms that best corresponds with improvement and remission. Symptom remission at endpoint (ADHD-RS-IV total score ≤18) was most closely aligned with a ≥46% reduction in ADHD-RS-IV total score. Clinical improvement was most closely aligned with a ≥40% reduction in ADHD-RS-IV total score. The three different measures of outcome were strongly aligned during double blind and open label treatment, and were independent of subtype status. Our data suggest that at least 40% improvement in symptoms is needed to achieve a robust response at endpoint.

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