Efficacy and safety of dexmethylphenidate extended-release capsules in adults with attention-deficit/hyperactivity disorder.
ABSTRACT This multicenter, randomized, fixed-dose, double-blind, placebo-controlled study evaluated efficacy of extended-release dexmethylphenidate (d-MPH-ER) in adults with attention-deficit/hyperactivity disorder (ADHD).
Randomized adults with ADHD (n=221) received once-daily d-MPH-ER 20 mg, 30 mg, or 40 mg or placebo for 5 weeks. The primary efficacy variable was change from baseline to final visit in DSM-IV ADHD Rating Scale (ADHD-RS) total score. Secondary efficacy parameters included the proportion of patients with improvement>or=30% in ADHD-RS total score and final scores on Clinical Global Impressions-Improvement (CGI-I) scale.
Of 218 evaluable patients, 184 completed the study. All d-MPH-ER doses were significantly superior to placebo in improving ADHD-RS total scores. Placebo scores improved by 7.9; d-MPH-ER, 20 mg, improved by 13.7 (p=.006); d-MPH-ER, 30 mg, improved by 13.4 (p=.012); and d-MPH-ER, 40 mg, improved by 16.9 (p<.001). Overall distribution of CGI-I ratings at final visit was significantly better with each d-MPH-ER dosage than with placebo. There were no unexpected safety or tolerability concerns, based on experience with racemic methylphenidate (MPH) in adults and dexmethylphenidate (d-MPH) in children.
Once-daily d-MPH-ER at 20 mg, 30 mg, or 40 mg is a safe and effective treatment for adults with ADHD.
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ABSTRACT: Objectives: To examine the clinical effects of equivalent doses of single-blind (SB; patient-blind) lisdexamfetamine (LDX) and mixed amphetamine salts-immediate release (MAS-IR) on adult attention-deficit/hyperactivity disorder (ADHD) in a placebo (PBO)-controlled, crossover design. Methods: Twenty-four subjects were treated sequentially in a fixed order with (1) SB PBO (matching LDX) for 1 week, (2) SB LDX (up to 70 mg/day) for 5 weeks, (3) SB PBO washout for 3 weeks, and (4) open-label treatment MAS-IR (tid up to 45 mg/day) for 5 weeks. Clinical effects on ADHD and executive function were assessed weekly throughout the trial with the ADHD Rating Scale with adult prompts, the Clinical Global Impression Severity Scale (CGI-S), and the Behavior Rating Inventory of Executive Function (BRIEF). Results: Lisdexamfetamine and MAS-IR were generally well tolerated. Significant and equal reductions on ADHD clinician ratings were seen. Significantly greater reductions in CGI-S and selected BRIEF subsets were observed in LDX over MAS-IR treatment. However, in general, baseline scores for MAS-IR treatment did not fully return to the LDX baseline. Adherence in this structured and monitored clinical trial was good for once daily LDX and 3 times a day MAS-IR. Conclusions: In this crossover study, both LDX and MAS-IR had significant effects on ADHD clinician ratings and measures of executive function (with response rates of about 80%); patients in this monitored clinical trial were adherent with once daily LDX and 3 times a day MAS-IR, which may not be the case in real-world clinical practice. The findings of some superiority of LDX over MAS-IR on the CGI-S and BRIEF ratings may be influenced by the variability in the baselines used, but nevertheless should be further investigated in larger scale, parallel-design clinical trials.Postgraduate Medicine 09/2014; 126(5):17-24. DOI:10.3810/pgm.2014.09.2796 · 1.54 Impact Factor
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ABSTRACT: El objetivo del presente estudio fue valorar la asociación entre los déficits de la función ejecutiva (DFE) y la respuesta al tratamiento con metilfenidato en adultos con trastorno por déficit de atención con hiperactividad (TDAH). Efectuamos un estudio aleatorizado, controlado con placebo, con un diseño de grupos paralelos y de 6 semanas de duración entre adultos con TDAH diagnosticados según los criterios del DSM-IV. Para el índice psicométrico de la función ejecutiva se utilizaron exámenes neuropsicológicos estandarizados. Evaluamos las conductas reflejas de DFE utilizando el cuestionario Behavior Rating Inventory of Executive Function, versión para el adulto (BRIEF-A). Se incluyeron para el análisis los individuos con parámetros disponibles del funcionamiento ejecutivo (tratados con MPH OROS, n = 40; tratados con placebo n = 47). No hubo una diferencia en el porcentaje de individuos que completaron la fase i del ensayo sobre eficacia aguda, de 6 semanas de duración (100% [n = 40] frente al 98% [n = 46]; p = 0,4). Al concluir el período de observación de la fase i la dosis diaria media de MPH OROS era de 84,6 ± 31,6 mg (1,04 ± 0,29 mg/kg) y la de placebo de 100,5 ± 21,9 mg (1,20 ± 0,11 mg/kg) (p = 0,0007). En función de los exámenes neuropsicológicos realizados en la valoración basal, se consideró que el 40% de individuos con TDAH (n = 35/87) experimentaba DFE pero, en la escala clínica BRIEF-A, en el 93% de individuos (n = 81) se identificaron ≥ 2 puntuaciones T > 65. Sin embargo, con independencia de la definición utilizada, los DFE no tuvieron una influencia en la respuesta clínica al tratamiento con MPH OROS. El presente ensayo clínico aleatorizado reveló que los déficit de la función ejecutiva no moderan la respuesta al metilfenidato y los parámetros de los déficit de la función ejecutiva no se asocian a la respuesta al tratamiento con MPH OROS.01/2012; 19(1):1-8. DOI:10.1016/j.psiq.2012.02.004
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ABSTRACT: The relationship between attention-deficit/hyperactivity disorder (ADHD) symptoms and global clinical assessment of functionality is complex. This post-hoc analysis explores this relationship and suggests implications for patient assessment in clinical practice. Adults with ADHD on a stable lisdexamfetamine dimesylate (LDX) dose for ≥ 6 months were enrolled in a double-blind, placebo-controlled, randomized withdrawal study. Participants entered a 3-week open-label phase continuing their prior LDX dose and were then randomized to placebo or the same LDX dose for a 6-week, double-blind, randomized withdrawal phase. ADHD symptom distribution was measured by the ADHD Rating Scale IV (ADHD-RS-IV) with Adult Prompts total score reflecting DSM-IV-TR ADHD symptom criteria and severity by Clinical Global Impressions-Severity (CGI-S) ratings at study entry and at end of study. Of 123 participants enrolled in the open-label phase, 116 were included in the randomized withdrawal phase (placebo, n = 60; LDX, n = 56). As reported in a prior publication, mean (standard deviation) ADHD-RS-IV total score change from baseline (week 3) to end of study (randomized-withdrawal phase) was 16.8 (11.80) for placebo and 1.6 (8.63) for LDX. At end of study, for placebo and LDX, 5.0% and 32.1% of participants, respectively, had a CGI-S = 1, 11.7% and 35.7% had a CGI-S = 2, 11.7% and 17.9% had a CGI-S = 3, 33.3% and 7.1% had a CGI-S = 4, 35.0% and 7.1% had a CGI-S = 5, and 3.3% and 0% had a CGI-S = 6; no participants had a CGI-S = 7 (P < 0.0001). The CGI-S ratings increased (worsened) as ADHD symptom scores worsened. Post-hoc regression analysis between ADHD-RS-IV scores and CGI-S demonstrated shared variance of 47% at week 3 and 69% for both placebo and LDX at end of study. Although ADHD symptom scores demonstrate a linear relationship with global illness severity, the variance suggests that other factors not captured by symptom scales are also important in assessing patient outcomes in clinical practice. (Trial registration: ClinicalTrials.gov NCT00877487.).Postgraduate Medicine 09/2014; 126(5):31-41. DOI:10.3810/pgm.2014.09.2798 · 1.54 Impact Factor