Predictors of Placebo Response in Adults With Attention-Deficit/Hyperactivity Disorder: Data From 2 Randomized Trials of Osmotic-Release Oral System Methylphenidate
ABSTRACT To find potential correlates of placebo response in adults with attention-deficit/hyperactivity disorder (ADHD) and gain insights into why placebo response may be high in clinical trials.
Post hoc analysis of placebo data from 2 randomized controlled trials of osmotic-release oral system (OROS) methylphenidate in adults with ADHD defined according to the Diagnostic and Statistical Manual of Mental Diseases, Fourth Edition: the Long-Acting Methylphenidate in Adults with ADHD (LAMDA-I) study (2005-2006, 5 weeks, n = 95) and the LAMDA-II study (2008-2009, 13 weeks, n = 97). The primary efficacy measure was the Conners' Adult ADHD Rating Scale-observer rated, short version (CAARS:O-SV). Predictors of CAARS:O-SV change were assessed using a random-intercepts model with demographic and disease-related parameters as independent variables. Sensitivity analyses were conducted using the CAARS self-report (CAARS:S-S) and a categorical response criterion (improvement of > 30% in CAARS:O-SV), and in subjects who completed the study.
In LAMDA-I, mean ± SD change in CAARS:O-SV was -7.6 ± 9.9 with placebo and -11.9 ± 10.6 with OROS methylphenidate. Higher baseline CAARS score (P = .007) and lower educational achievement (P = .014) were significantly associated with greater improvement in placebo-treated subjects. In LAMDA-II, mean ± SD change in CAARS:O-SV was -10.4 ± 11.0 and -14.1 ± 10.7 in subjects receiving placebo and OROS methylphenidate, respectively. Variables significantly associated with greater placebo response were higher baseline CAARS:O-SV (P = .019), shorter time since ADHD diagnosis (P < .045), and younger age (P = .014). None of the sensitivity analyses challenged the outcomes.
Possible predictors of placebo response in adults with ADHD include higher severity of ADHD symptoms, younger age, shorter time since diagnosis, and lower educational level.
ClinicalTrials.gov identifier: NCT00246220 (LAMDA-I) and EudraCT number: 2007-002111-82 (LAMDA-II).
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ABSTRACT: Abstract Objective: The purpose of this study was to find potential variables associated with the difference between subjective and object treatment responses in children with attention-deficit/hyperactivity disorder (ADHD) treated with OROS-methylphenidate (MPH). Methods: We conducted a post-hoc analysis of data from a multicenter, open-label, 12 week trial of OROS-MPH in Korean children with ADHD. The subjective outcome measurement was the parent version of the ADHD Rating Scale-IV (ARS-P), and the objective outcome measurement was the Continuous Performance Test (CPT). We compared the children's demographic and disease-related variables among four groups, classified according to whether they showed subjective or objective improvement after MPH treatment. Results: Higher baseline inattentive scores on the ARS-P were associated with a significantly higher probability of subjective treatment response among objective nonresponders (p=0.033). Lower baseline inattentive scores on the ARS-P were associated with a significantly higher probability of subjective nonresponse among objective responders (p=0.045). Lower baseline omission errors (p=0.006) and response time variability scores (p=0.011) on the CPT were associated with a significantly higher probability of both objective and subjective responses, compared with both types of nonresponse to treatment. Conclusions: The baseline severity of parent-perceived inattentive symptoms was predictive of differences in subjective and objective treatment responses, and the baseline severity of neuropsychological deficit (inattention and inconsistency of attention) was predictive of responses, using both subjective and objective measurements.Journal of child and adolescent psychopharmacology 08/2013; 23(6):410-4. DOI:10.1089/cap.2013.0031 · 3.07 Impact Factor
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ABSTRACT: Although the identification of reliable predictors of methylphenidate response in adults with attention-deficit/hyperactivity disorder (ADHD) is necessary to guide treatment decisions, very few data exist on this issue. Here, we assessed the predictors of clinical response to immediate-release methylphenidate hydrochloride (IR-MPH) in a naturalistic setting by analyzing the influence of demographic factors, severity, and a wide range of comorbid psychiatric disorders. Two hundred fifty adult patients with ADHD were evaluated and completed a short-term treatment with IR-MPH. Mental health diagnoses were based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria through the use of standard structured interviews. The Swanson, Nolan, and Pelham Rating Scale, version 4, adapted to adults was used to assess the severity of ADHD. In the linear regression model, only higher severity of ADHD was associated to a better IR-MPH response (b = 0.770; P < 0.001). Treatment of comorbidities in a subsample (n = 62) did not modify this pattern. Our findings suggest that in clinical settings, patients with more severe ADHD symptoms have a good response to treatment independently from the presence of mild or stabilized comorbidities and their treatments. For adults with ADHD, differently from other common psychiatric disorders such as depression and anxiety, higher severity is associated with better treatment response.Journal of clinical psychopharmacology 04/2014; 34(2):212-7. DOI:10.1097/JCP.0000000000000091 · 3.76 Impact Factor
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ABSTRACT: Predictors of the placebo response (PR) in randomized controlled trials (RCT) have been searched for ever since RCT have become the standard for testing novel therapies and age and gender are routinely documented data in all trials irrespective of the drug tested, its indication, and the primary and secondary end points chosen. To evaluate whether age and gender have been found to be reliable predictors of the PR across medical subspecialties, we extracted 75 systematic reviews, meta-analyses, and meta-regressions performed in major medical areas (neurology, psychiatry, internal medicine) known for high PR rates. The literature database used contains approximately 2,500 papers on various aspects of the genuine PR. These 'meta-analyses' were screened for statistical predictors of the PR across multiple RCT, including age and gender, but also other patient-based and design-based predictors of higher PR rates. Retrieved papers were sorted for areas and disease categories. Only 15 of the 75 analyses noted an effect of younger age to be associated with higher PR, and this was predominantly in psychiatric conditions but not in depression, and internal medicine but not in gastroenterology. Female gender was associated with higher PR in only 3 analyses. Among the patient-based predictors, the most frequently noted factor was lower symptom severity at baseline, and among the design-based factors, it was a randomization ratio that selected more patients to drugs than to placebo, more frequent study visits, and more recent trials that were associated with higher PR rates. While younger age may contribute to the PR in some conditions, sex does not. There is currently no evidence that the PR is different in the elderly. PR are, however, markedly influenced by the symptom severity at baseline, and by the likelihood of receiving active treatment in placebo-controlled trials. © 2014 S. Karger AG, Basel.Gerontology 11/2014; 61(2). DOI:10.1159/000365248 · 2.68 Impact Factor