Duration of effect of oral long-acting stimulant medications for ADHD throughout the day

Baylor College of Medicine, Houston, TX, USA.
Current Medical Research and Opinion (Impact Factor: 2.65). 08/2010; 26(8):1809-25. DOI: 10.1185/03007995.2010.488553
Source: PubMed


To examine duration of efficacy in long-acting stimulant treatment of attention-deficit/hyperactivity disorder (ADHD) in clinical trials using analog classroom protocols.
Published reports of clinical trials examining duration of medication efficacy using analog classroom protocols were identified in a systematic literature search of PubMed, BIOSYS, and EMBASE, through June 2009 using combinations of terms: attention-deficit/hyperactivity disorder, ADHD, attention-deficit disorder with hyperactivity, stimulant, methylphenidate (MPH), amphetamine, laboratory school or classroom, analog classroom, math test, and Permanent Product Measure of Performance (PERMP). Reports of short-acting, nonoral or nonstimulant formulations, or inadequate data on duration of efficacy were excluded.
Main outcomes examined were PERMP scores for number of math problems attempted (PERMP-A) and correctly answered (PERMP-C) based on a standard 10-minute math test given at regular intervals during the postdose period.
Fifteen trials were included in the analysis. All except one trial in adults (18-55 years) were conducted in children with ADHD (6-15 years) and employed randomized, double- or single-blind, placebo-controlled designs. Duration of efficacy, based on PERMP-A/-C scores (vs. placebo), ranged from 8 hours with long-acting MPH to 14 hours with lisdexamfetamine dimesylate; most formulations exerted therapeutic effects for 12 hours after a single morning dose. Duration of efficacy assessment may be limited by duration of observation (12 hours postdose for most studies). Outcomes may have been influenced by differences in study designs, population characteristics, lack of comparable, equivalent dosages of different extended-release stimulants, and limited ability to extrapolate safety and tolerability from short-term studies to long-term clinical use. Results from cross-study comparisons must be interpreted with caution.
Most long-acting stimulants exerted beneficial effects on ADHD symptoms for up to 12 hours as measured by the PERMP; the longest duration of efficacy versus placebo was seen with lisdexamfetamine dimesylate (14 hours postdose).

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    • "Consideration of the onset and duration of efficacy of long-acting MPH formulations in the context of the patient’s individual needs when selecting an appropriate formulation was highlighted [19,52,53]. The pattern of efficacy generally follows that predicted by the PK profile of the MPH formulation [53]. "
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    ABSTRACT: The stimulant methylphenidate (MPH) has been a mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD) for many years. Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations, a new generation of long-acting MPH formulations has emerged. Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy; however, to date, relatively few head-to-head studies have been performed.The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection. A systematic literature search was conducted in MEDLINE and PsycINFO in March 2012 using the MeSH terms: attention deficit disorder with hyperactivity/drug therapy; methylphenidate/therapeutic use and All Fields: Concerta; Ritalin LA; OROS and ADHD; Medikinet; Equasym XL and ADHD; long-acting methylphenidate; Diffucaps and ADHD; SODAS and methylphenidate. No filters were applied and no language, publication date or publication status limitations were imposed. Articles were selected if the title indicated a comparison of two or more long-acting MPH preparations in human subjects of any age; non-systematic review articles and unpublished data were not included. Of 15,295 references returned in the literature search and screened by title, 34 articles were identified for inclusion: nine articles from pharmacokinetic studies (nine studies); nine articles from laboratory school studies (six studies); two articles from randomized controlled trials (two studies); three articles from switching studies (two studies) and three articles from one observational study. Emerging head-to-head studies provide important data on the comparative efficacy of the formulations available. At a group level, efficacy across the day generally follows the pharmacokinetic profile of the MPH formulation. No formulation is clearly superior to another; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment. For patients achieving suboptimal symptom control, switching long-acting MPH formulations may be beneficial. When switching formulations, it is usually appropriate to titrate the immediate-release component of the formulation; a limitation of current studies is a focus on total daily dose rather than equivalent immediate-release components. Further studies are necessary to provide guidance in clinical practice, particularly in the treatment of adults and pre-school children and the impact of comorbidities and symptom severity on treatment response.
    BMC Psychiatry 09/2013; 13(1):237. DOI:10.1186/1471-244X-13-237 · 2.21 Impact Factor
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    • "This may result in a need for medication supply and reliance on the school nurse for administration, and has the potential for nonadherence and social stigmatism.14 The long-acting oral stimulant preparations are usually dosed once a day and their duration of activity is generally 7–12 hours, depending on the product.15,16 They offer improved adherence and greater dosing convenience; however, concerns about the abuse potential of stimulants exist and have led to the development of newer formulations addressing this issue. "
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    ABSTRACT: Attention-deficit/hyperactivity disorder is one of the most common neurobehavioral disorders defined by developmentally inappropriate levels of inattention, hyperactivity, and impulsivity. Symptoms begin in childhood and may persist into adolescence and adulthood. Currently available pharmacological treatment options for attention-deficit/hyperactivity disorder in children and adolescents include stimulants that are efficacious and well tolerated; however, many of these preparations require multiple daily dosing and have the potential for abuse. Lisdexamfetamine dimesylate, the first prodrug stimulant, was developed to provide a longer duration of effect. It demonstrates a predictable delivery of the active drug, d-amphetamine, with low interpatient variability, and has a reduced potential for abuse. A literature search of the MEDLINE database and clinical trials register from 1995-2011, as well as relevant abstracts presented at annual professional meetings, on lisdexamfetamine dimesylate in children and adolescents were included for review. This article presents the pharmacokinetic profile, efficacy, and safety of lisdexamfetamine dimesylate for the treatment of attention-deficit/hyperactivity disorder in children and, more recently, in adolescents.
    Adolescent Health, Medicine and Therapeutics 05/2012; 3:51-66. DOI:10.2147/AHMT.S19815
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    • "These long-term studies mostly comprise open-label extensions of controlled short-term trials, but also long-term controlled trials and observational studies of clinical cases are reported. Taken together, the limited data suggest maintenance of treatment response to stimulants over 6 months—2 years, without developing tolerance of treatment effects [24–29]. However, more data on long-term effects in different study populations are warranted to clarify and differentiate between long-term effects and effects of long-term treatment. "
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    ABSTRACT: In a recent randomized, double-blind, placebo-controlled trial, we established a robust efficacy (Cohen's d = 2.17) of osmotic release oral system-methylphenidate (OROS-methylphenidate) delivered 72 mg daily for 5 weeks versus placebo on attention deficit hyperactivity disorder (ADHD) symptoms, global severity and global functioning in 30 adult male prison inmates with ADHD and coexisting disorders. Outcomes continued to improve during the subsequent 47-week open-label extension with OROS-methylphenidate delivered at a flexible daily dosage of up to 1.3 mg/kg body weight. In the present study, we evaluated long-term effectiveness and maintenance of improvement over the cumulated 52-week trial on cognition, motor activity, institutional behaviour and quality of life. Post hoc, we explored the associations between investigators' and self-ratings of ADHD symptoms and between ratings of symptoms and functioning, respectively. Outcomes, calculated by repeated measures ANOVA, improved from baseline until week 16, with maintenance or further improvement until week 52. Both verbal and visuospatial working memory, and abstract verbal reasoning improved significantly over time, as well as several cognition-related measures and motor activity. No substance abuse was detected and a majority of participants took part in psychosocial treatment programmes. The quality of life domains of Learning, and Goals and values improved over time; the latter domain was at open-label endpoint significantly related to improvements in attention. Investigators' and self-ratings of ADHD symptoms, as well as global symptom severity related most significantly to global functioning at week 52. Finally, investigators' and self-ratings of ADHD symptoms associated significantly at baseline with increasing convergence over time.
    European Archives of Psychiatry and Clinical Neuroscience 04/2012; 262(8). DOI:10.1007/s00406-012-0317-8 · 3.53 Impact Factor
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