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Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies.

Coghill D, Banaschewski T, Zuddas A, Pelaz A, Gagliano A, Doepfner M - BMC Psychiatry (2013)

Bottom Line: 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.No formulation is clearly superior to another; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Neuroscience, Medical Research Institute, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. d.r.coghill@dundee.ac.uk.

ABSTRACT

Background: 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.

Methods: 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comparison of two or more long-acting MPH preparations in human subjects of any age; non-systematic review articles and unpublished data were not included.

Results: 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.

Conclusions: 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.

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Comparative efficacy of Concerta®(d,l-MPH-ER; 36, 54 mg) and Focalin XR®(d-MPH-ER; 20, 30 mg) versus placebo over time in a laboratory school study. SKAMP, Swanson, Kotkin, Atkins, M-Flynn, Pelham rating scale. Error bars: standard deviation. Reprinted/Reproduced from Silva R, et al. Psychopharmacol Bull 2008, 41:19–33, with permission from MedWorks Media Global, LLC.
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Figure 4: Comparative efficacy of Concerta®(d,l-MPH-ER; 36, 54 mg) and Focalin XR®(d-MPH-ER; 20, 30 mg) versus placebo over time in a laboratory school study. SKAMP, Swanson, Kotkin, Atkins, M-Flynn, Pelham rating scale. Error bars: standard deviation. Reprinted/Reproduced from Silva R, et al. Psychopharmacol Bull 2008, 41:19–33, with permission from MedWorks Media Global, LLC.

Mentions: Focalin XR® was superior to higher daily doses of Concerta® (20 versus 36 mg, and 30 versus 54 mg, respectively) at 0.5–6 hours post-dose [18,33]. Two head-to-head laboratory school comparisons of Focalin XR® with higher daily doses of Concerta® (20 versus 36 mg, and 30 versus 54 mg, respectively) demonstrated that Focalin XR® had an earlier onset of efficacy compared with Concerta®, with significantly greater improvements from baseline in SKAMP-Combined, SKAMP-Attention, SKAMP-Deportment scores and math test scores with Focalin XR® than with Concerta® at time points between 0.5 and 6 hours post-dose [18,33] (Figure 4). Post-hoc analyses of AUC0–6 for SKAMP-Combined scores showed trends nearing statistical significance in favour of Focalin XR® over Concerta® (Focalin XR® 20 mg versus Concerta® 36 mg, p = 0.074; Focalin XR® 30 mg versus Concerta® 54 mg, p = 0.068) [33]. Significantly greater improvements from baseline with Focalin XR® compared with Concerta® were also observed in Math-Attempted and Math-Correct scores at 3 hours (20 versus 36 mg) and 4–5 hours (30 versus 54 mg) post-dose [18,33].


Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies.

Coghill D, Banaschewski T, Zuddas A, Pelaz A, Gagliano A, Doepfner M - BMC Psychiatry (2013)

Comparative efficacy of Concerta®(d,l-MPH-ER; 36, 54 mg) and Focalin XR®(d-MPH-ER; 20, 30 mg) versus placebo over time in a laboratory school study. SKAMP, Swanson, Kotkin, Atkins, M-Flynn, Pelham rating scale. Error bars: standard deviation. Reprinted/Reproduced from Silva R, et al. Psychopharmacol Bull 2008, 41:19–33, with permission from MedWorks Media Global, LLC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852277&req=5

Figure 4: Comparative efficacy of Concerta®(d,l-MPH-ER; 36, 54 mg) and Focalin XR®(d-MPH-ER; 20, 30 mg) versus placebo over time in a laboratory school study. SKAMP, Swanson, Kotkin, Atkins, M-Flynn, Pelham rating scale. Error bars: standard deviation. Reprinted/Reproduced from Silva R, et al. Psychopharmacol Bull 2008, 41:19–33, with permission from MedWorks Media Global, LLC.
Mentions: Focalin XR® was superior to higher daily doses of Concerta® (20 versus 36 mg, and 30 versus 54 mg, respectively) at 0.5–6 hours post-dose [18,33]. Two head-to-head laboratory school comparisons of Focalin XR® with higher daily doses of Concerta® (20 versus 36 mg, and 30 versus 54 mg, respectively) demonstrated that Focalin XR® had an earlier onset of efficacy compared with Concerta®, with significantly greater improvements from baseline in SKAMP-Combined, SKAMP-Attention, SKAMP-Deportment scores and math test scores with Focalin XR® than with Concerta® at time points between 0.5 and 6 hours post-dose [18,33] (Figure 4). Post-hoc analyses of AUC0–6 for SKAMP-Combined scores showed trends nearing statistical significance in favour of Focalin XR® over Concerta® (Focalin XR® 20 mg versus Concerta® 36 mg, p = 0.074; Focalin XR® 30 mg versus Concerta® 54 mg, p = 0.068) [33]. Significantly greater improvements from baseline with Focalin XR® compared with Concerta® were also observed in Math-Attempted and Math-Correct scores at 3 hours (20 versus 36 mg) and 4–5 hours (30 versus 54 mg) post-dose [18,33].

Bottom Line: 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.No formulation is clearly superior to another; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Neuroscience, Medical Research Institute, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. d.r.coghill@dundee.ac.uk.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus