A randomised, placebo-controlled, 24-week, study of low-dose extended-release methylphenidate in adults with attention-deficit/hyperactivity disorder

European Archives of Psychiatry and Clinical Neuroscience (Impact Factor: 3.53). 02/2009; 259(2):120-129. DOI: 10.1007/s00406-008-0845-4


Attention-deficit/hyperactivity disorder (ADHD) affects many adults who had ADHD in childhood. Although stimulants and methylphenidate in particular are a common off-label treatment for adult patients with ADHD in European countries, little is known about their long-term efficacy and safety.

A randomized, 24-week double-blind, placebo-controlled, parallel-design study of extended-release methylphenidate (MPH ER) in 359 adult individuals with ADHD according to DSM-IV. Standardized instruments were used for diagnosis. Treatment was started with MPH ER doses of 10 mg/day and titrated up to 60 mg/day, depending on individual efficacy and tolerability. Mean daily MPH SR dose was 0.55 mg/kg.

Treatment with MPH ER resulted in clinical and statistically significant reductions of ADHD symptoms rated with the Wender-Reimherr adult attention deficit disorder scale (WRAADDS) and symptoms of inattention and hyperactivity/impulsivity according to DSM-IV, respectively. Improvements were maintained significant versus placebo up to week 24 of treatment. At endpoint, 61% of the subjects receiving MPH ER were rated as responders according to the a priori definition of response of more than 30% reduction of the WRAADDS score, compared to 42% in the placebo group. The second defined response criterion of much or very much improved on the clinical global impression scale (CGI) was fulfilled by 55% of subjects receiving MPH ER and 37% of subjects receiving placebo. MPH ER treatment was associated with a statistically significant increase of pulse at week 4 (72 bpm at baseline, 77 bpm at week 4). There were no significant differences of heart rate or blood pressure between treatment and placebo groups at any time point.

MPH ER treatment in low to moderate doses was effective and safe in the treatment of ADHD in adults. Efficacy measures were clinical and statistically significant and robustly sustained during the 24-week observation period. In this study, no clinical significant effects on blood pressure but a transient increase of the heart rate were found. The interpretation of the results is limited by the low dose-range used in this study, the high drop-out rate and placebo-response which might have affected the therapeutic effect size.

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    • "The WRAADDS and its predecessors have been used in clinical trials both in the identification of patients and assessment of treatment effects. These studies include methylphenidate immediate release (Wender, Reimherr, & Wood, 1981; Wender, Reimherr, Wood, & Ward, 1985; Wood et al., 1976), methylphenidate extended release (Rösler, Fisher, Ammer, Ose, & Retz, 2009), osmotic release oral system methylphenidate (OROS MPH; Reimherr et al., 2007), methylphenidate transdermal system (MTS; Marchant, Reimherr, Robison, Olsen, & Kondo, 2010), L-dopa/ carbidopa (Reimherr, Wood, & Wender, 1980), pemoline (Wender et al., 1981), pargyline (Wender, Wood, Reimherr, & Ward,1983), l-deprenyl (Wood, Wender, & Reimherr, 1983), dl-phenylalanine (Wood, Reimherr, & Wender, 1985), l-tyrosine (Reimherr, Wender, Wood, & Ward, 1987), nomifensine (Shekim, Masterson, Cantwell, Hanna, & McCracken, 1989), bupropion (Wender & Reimherr, 1990), venlafaxine (Reimherr, Hedges, Rogers, Strong, & Wender, 1995), and atomoxetine (Michelson et al., 2003). It has also been used for phenotypic determination in genetic and imaging studies (Retz, Thome, Blocher, Baader, & Rösler, 2002; Robison et al., 2010; Zametkin et al., 1990). "
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    ABSTRACT: The Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS; Wender, 1995) is a clinician-rated scale based on the Utah Criteria for attention-deficit/hyperactivity disorder (ADHD) in adults. It assesses ADHD symptom severity across 7 domains: attention difficulties, hyperactivity/restlessness, temper, affective lability, emotional over-reactivity, disorganization, and impulsivity. The normative sample consisted of 120 males and females ages 20-49 with no personal or family history of ADHD. Patients with ADHD met Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000) criteria, included males and females ages 20-60, and came from 5 clinical trials. Measures of reliability (test-retest r = .96; interrater r = .75) and internal consistency (Cronbach's alpha = 0.78) were acceptable. The WRAADDS correlated with the Conners' Adult ADHD Rating Scale (CAARS; Conners, Erhardt, & Sparrow, 1999) total scores (r = .501, p < .001). WRAADDS hyperactivity + impulsivity correlated with the CAARS hyperactivity/impulsivity (r = .601, p < .001), and WRAADDS attention + disorganization correlated with the CAARS inattention (r = .430, p < .001). Discriminate validity (adults with vs. without ADHD) was significant for all domains (p < .001). Factor analysis yielded a 2-factor solution accounting for 58% of the variance, one containing the emotional dimensions and the second containing attention and disorganization. Hyperactivity/restlessness and impulsivity were split between both factors. Changes in response to treatment for the WRAADDS and CAARS were highly correlated (p < .001). These psychometric data support continued use of the WRAADDS in adults with ADHD. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
    Full-text · Article · May 2013 · Psychological Assessment
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    ABSTRACT: Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in young adults and causes significant psychosocial impairment and economic burden to society. Because of the paucity of long-term evidence and lack of national guidelines for diagnosis and management of adult ADHD, most of the data are based on experience derived from management of childhood ADHD. This article reviews the current evidence for the diagnosis and management of adult ADHD with special emphasis on the role of methylphenidate hydrochloride preparations in its treatment. Methylphenidate hydrochloride, a stimulant that acts through the dopaminergic and adrenergic pathways, has shown more than 75% efficacy in controlling the symptoms of adult ADHD. Although concern for diversion of the drug exists, recent data have shown benefits in preventing substance use disorders in patients with adult ADHD.
    Preview · Article · Feb 2009 · Neuropsychiatric Disease and Treatment
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    ABSTRACT: The goal of the study was twofold: (1) to investigate the effect of different diagnostic criteria on prevalence estimates of adult attention deficit hyperactivity disorder (ADHD), and (2) to provide prevalence estimates of adult ADHD for the first time in a Hungarian sample. Subjects between 18 and 60 years were included in the screening phase of the study (N = 3,529), conducted in 17 GP practices in Budapest. Adult self-report scale 6-item version was used for screening. Out of 279 positively screened subjects 161 subjects participated in a clinical interview and filled out a self-report questionnaire to confirm the diagnosis. Beside DSM-IV diagnostic criteria, we applied four alternative diagnostic criteria: 'No-onset' (DSM-IV criteria without the specific requirement for onset); full/Sx (DSM-IV "symptoms only" criteria); and reduced/Sx (DSM-IV "symptoms only" criteria with a reduced threshold for symptom count). Crude prevalence estimates adjusted for the specificity and sensitivity data of the screener were 1.35% in the 'DSM-IV' group, 1.64% in the 'No-onset' group, 3.65% in the 'Sx/full' group and 4.16% in the 'Sx/reduced' group. Logistic regression analysis showed that ADHD was significantly more prevalent with younger age and male gender [chi(2) = 14.46; P = 0.0007]. Prevalence estimates corrected for the 'not-interviewed' subsample and adjusted for specificity and sensitivity data of the screener was 2.3% in males, 0.91% in females; 2.02% in the < or =40 years age group and 0.70% in the >40 years age group, based on DSM-IV diagnostic criteria. Prevalence rates found in this study are somewhat lower, but still are in line with those reported in the literature.
    No preview · Article · Oct 2009 · European Archives of Psychiatry and Clinical Neuroscience
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