Post hoc analyses of the impact of previous medication on the efficacy of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in a randomized, controlled trial

Coghill, David; Banaschewski, Tobias; Lecendreux, Michel; Soutullo, César; Zuddas, Alessandro; Adeyi, Ben; Sorooshian, Shaw

doi:10.2147/ndt.s68273

Cited by 14 publications

(13 citation statements)

References 22 publications

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“…SPD489-325 (ClinicalTr ials.gov identif ier: NCT00763971) was a 7-week, double-blind, efficacy and safety study of LDX in children and adolescents (aged 6-17 years) with ADHD and an ADHD-RS-IV total score of at least 28, conducted in Europe (48 sites in 10 countries). Details of the study design, results and previous post hoc analyses have been published [10,15,[17][18][19][20][21].…”

Section: Study Designs and Populationsmentioning

confidence: 99%

Functional impairment outcomes in clinical trials of different ADHD medications: post hoc responder analyses and baseline subgroup analyses

Coghill

Werner‐Kiechle

Farahbakhshian

et al. 2020

Eur Child Adolesc Psychiatry

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Several recent phase 3 clinical trials of attention-deficit/hyperactivity disorder (ADHD) medications have used the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P). Here, we assess WFIRS-P response in individual patients in two pivotal trials of lisdexamfetamine dimesylate (LDX) and guanfacine extended release (GXR). We also analysed pooled WFIRS-P data from seven phase 3 studies of ADHD medications to shed light on factors associated with baseline functional impairment. The proportion of patients with a change in WFIRS-P score that exceeded the minimal important difference (MID) criteria for response was greater for LDX than placebo in the Family, Learning and School, and Risky Activities domains, and was greater for GXR than placebo in the Social Activities, Learning and School, and Family domains. Responders had significantly worse baseline scores in all WFIRS-P domains (all p < 0.001) than non-responders. In the pooled analyses, baseline WFIRS-P scores in all domains were significantly worse in participants with oppositional defiant disorder (ODD) than in those without ODD. Having combined type or hyperactive-impulsive type ADHD, being enrolled into a study in Europe, being male and being younger also had modest negative effects on baseline WFIRS-P scores. The present analysis of WFIRS-P response shows that previously reported group-level improvements in WFIRS-P functional impairment score translated into clinically relevant improvements in many individual participants. Functional impairment is a diverse and subjective construct that is influenced by multiple factors. Optimal management of individuals with ADHD should involve monitoring improvements in functioning and quality of life, as well as symptomatic improvement.

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Section: Study Designs and Populationsmentioning

confidence: 99%

Functional impairment outcomes in clinical trials of different ADHD medications: post hoc responder analyses and baseline subgroup analyses

Coghill

Werner‐Kiechle

Farahbakhshian

et al. 2020

Eur Child Adolesc Psychiatry

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“…Besides, our results suggested that MPH is a good candidate, especially with regards to fatigue and the rate of withdrawal, which makes MPHas the routine therapy clinically. LDX is used for patients with ADHD who have an inadequate response to MPH ( 12 , 14 ). Although MPH releases quickly in vivo as a stimulant, it can be controlled by modification, which is documented as osmotic release oral system ( 37 , 41 , 51 , 83 ), leading to moderate side effects ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

“…Lisdexamfetamine dimesylate (LDX) is a stimulant, normally used as a monotherapy or supplement for psychostimulants in ADHD treatment ( 10 , 11 ). In general, LDX is employed as prodrug due to its fast absorption and hydroxylation, which leads to a gradual and long lasting release ( 12 – 14 ). Methylphenidate (MPH) is a psych stimulant and is considered as the first-line therapy ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Tolerability of Different Interventions in Children and Adolescents with Attention Deficit Hyperactivity Disorder

Luan

Yue

et al. 2017

Front. Psychiatry

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BackgroundOur study is an analysis of multiple publications involving assessing the comparable efficacy and tolerability of six interventions, which are lisdexamfetamine dimesylate (LDX), atomoxetine (ATX), methylphenidate (MPH), clonidine hydrochloride (CLON), guanfacine extended release (GXR), and bupropion, for young patients (6–18 years old) suffering from attention deficit hyperactivity disorder (ADHD).MethodsA conventional meta-analysis (MA) was performed to give direct comparisons and a network meta-analysis (NMA) was used to show the combination of direct and indirect evidence. Ranking preference for all the interventions under a certain outcome was given by the surface of cumulative ranking curve area (SUCRA).ResultsOverall, 15,025 participants from 73 studies were involved in our analysis. In the pairwise MA, LDX was associated with less withdrawal than ATX for lack of efficacy. MPH showed less effectiveness than LDX according to ADHD Rating Scale score. Based on the analysis of our NMA, significant results of efficacy that LDX is a competitive drug were observed when evaluating LDX in comparison with other drugs except for CLON. ATX and GXR presented higher rates of abdominal pain morbidity versus inactive treatment.ConclusionThe stimulants LDX and MPH are still highly recommended because they are highly effective and are tolerated well by patients. Among the non-stimulants, CLON can be taken into consideration for its appreciable effectiveness and tolerability. ATX and GXR can be seen as moderate choices.

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“…Responder analyses are widely accepted in the field, although there is currently no consensus regarding the most appropriate response criteria; previous analyses of ADHD treatments have employed specified percentage reductions from baseline in ADHD-RS-IV total score, a CGI-I score of 1 or 2, or a combination of the two. 3 , 29 – 31 The use of different levels of response in the present study provides information at different levels of stringency. Response rates decreased with increasingly stringent definitions, as would be expected.…”

Section: Discussionmentioning

confidence: 99%

“… 19 Finally, it should be noted that this study found a numerically but nominally statistically nonsignificant larger placebo response in the stimulant-naïve group than in the prior MPH group, supporting other research suggesting that previous MPH exposure may influence the placebo response. 17 , 29 Future research, therefore, should specifically address the question of whether prior exposure to MPH changes the outcome on subsequent pharmacological exposure.…”

Section: Limitationsmentioning

confidence: 99%

Guanfacine extended release for children and adolescents with attention-deficit/hyperactivity disorder: efficacy following prior methylphenidate treatment

Huß

Sikirica

Hervás³

et al. 2016

NDT

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Guanfacine extended release (GXR) and atomoxetine (ATX) are nonstimulant treatments for attention-deficit/hyperactivity disorder (ADHD). As nonstimulant treatments are often used after stimulants in ADHD, GXR was assessed relative to prior stimulant treatment in a randomized controlled trial (RCT), in which ATX was included as a reference arm, and in the open-label phase of a randomized-withdrawal study (RWS). Participants were 6–17 years old with ADHD Rating Scale version IV (ADHD-RS-IV) scores ≥32 and Clinical Global Impressions – Severity scores ≥4. RCT participants received dose-optimized GXR (1–7 mg/day), ATX (10–100 mg/day), or placebo for 10–13 weeks. RWS participants received dose-optimized GXR (1–7 mg/day) for 13 weeks. Participants’ last stimulant medication prior to enrolment, and reasons for stopping this medication, were collected at baseline. Change from baseline ADHD-RS-IV score and the proportion of responders were assessed by prior stimulant exposure. Of 163 RCT and 296 RWS participants who had previously received stimulant treatment, 142 and 224, respectively, had received methylphenidate (MPH); due to the low number of participants and the heterogeneity of non-MPH treatments, we only report data for prior MPH treatment. The most frequent reasons for stopping MPH were lack of effectiveness or side effects. Placebo-adjusted ADHD-RS-IV changes from baseline were significant in participants receiving GXR (prior MPH, −9.8, P<0.001, effect size [ES] 0.85; stimulant-naïve, −7.6, P<0.001, ES 0.65). In ATX-treated participants, significant placebo-adjusted differences were seen in stimulant-naïve (−5.0, P=0.022, ES 0.43) but not prior MPH-treated (−1.8, P>0.05, ES 0.15) participants. More participants met responder criteria with GXR versus placebo, regardless of prior treatment. GXR response was unaffected by prior stimulant treatment; ATX produced improvement only in stimulant-naïve participants relative to placebo. These findings may be relevant to clinical decision-making regarding sequencing of ADHD treatments.

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Post hoc analyses of the impact of previous medication on the efficacy of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in a randomized, controlled trial

Cited by 14 publications

References 22 publications

Functional impairment outcomes in clinical trials of different ADHD medications: post hoc responder analyses and baseline subgroup analyses

Functional impairment outcomes in clinical trials of different ADHD medications: post hoc responder analyses and baseline subgroup analyses

Efficacy and Tolerability of Different Interventions in Children and Adolescents with Attention Deficit Hyperactivity Disorder

Guanfacine extended release for children and adolescents with attention-deficit/hyperactivity disorder: efficacy following prior methylphenidate treatment

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