Declan Quinn - Academia.edu (original) (raw)
Papers by Declan Quinn
Journal of Child and Adolescent Psychopharmacology, 2007
Objective: The purpose of this study was to evaluate the comparative efficacy and safety of a nov... more Objective: The purpose of this study was to evaluate the comparative efficacy and safety of a novel long-duration multilayer-release (MLR) methylphenidate (MPH) formulation and immediate-release (IR) MPH in attention-deficit/hyperactivity disorder (ADHD) children. Patients and Methods: This study was a randomized, double-blind, crossover comparison of once-daily MLR and twice-daily IR-MPH in home and school settings in children with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of ADHD. Patients completed a 1-week baseline followed by two active medication titration phases. Each phase of treatment was 1-4 weeks of titration with an additional stable dose week. The final dose was based on efficacy and adverse events for each patient. Efficacy measures included Clinical Global Impressions (CGI) and Conners' Parent and Teacher Rating Scales (CPRS and CTRS). The Clinical Assessment of Side Effects (CASE) scale assessed frequency of adverse events. Results: Of the 90 enrolled patients, aged 6.4-17.5 years, 79 (88%) completed the study. Stable daily doses were 32.0 and 32.5 mg for MLR-and IR-MPH, respectively. All efficacy parameters were significantly improved from baseline. A total of 73.2% and 81.0% of patients on MLR-and IR-MPH were rated as "much" or "very much improved" on the CGI. A total of 77.4% and 81.1% of patients were normalized on the CPRS-R and 78.9 and 90.4% of patients were normalized on the CTRS-R for MLR-and IR-MPH, respectively. The mean CASE score was not different from baseline for either treatment.
Journal of the American Academy of Child & Adolescent Psychiatry, 2016
The goals of this session are as follows: 1) to describe the technology underlying amphetamine-ex... more The goals of this session are as follows: 1) to describe the technology underlying amphetamine-extended release-orally disintegrating tablets (AMP XR-ODTs), a novel formulation approved for the treatment of ADHD in patients 6 years of age and older; 2) to assess the effect of food on AMP XR-ODT and compare the rate of absorption and oral bioavailability of AMP XR-ODT with a reference drug [XR-mixed AMP salts (XR MAS)]. Methods: Adult volunteers were enrolled in a single-dose, open-label, threeperiod, three-treatment, randomized crossover pharmacokinetic (PK) study and received an 18.8-mg dose of AMP XR-ODT (fasted or fed) or equivalent dose of XR MAS (fasted). Blood samples were analyzed for dAMP and lAMP (predoseÀ60 h postdose). The following PK parameters were determined: maximum plasma concentration (C max), time to maximum plasma concentration (T max), and area-under-the-concentration-time curve from time zero to the last concentration (AUC last) and to infinity (AUC inf). Early (AUC 0-5) and late (AUC 5-last) exposure also were measured as supportive endpoints. Bioequivalence was established if the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs; AMP XR-ODT/reference drug) for C max and AUCs were within the range of 80 to 125 percent. The effect of food on absorption of AMP XR-ODT was evaluated by comparing C max and AUCs across conditions (fed vs. fasted). Safety also was assessed. Results: A total of 39 participants completed the study. AMP XR-ODT formulation displayed a PK profile similar to XR MAS (fasted). The GMRs (90% CI) for AMP XR-ODT/XR MAS were within 80-125 percent for dAMP and lAMP C max , AUC 5-last , AUC last , and AUC inf ; median T max was approximately 5 h for both products. The 90% CI for AUC 0-5 was slightly below the 80-125 percent interval, possibly because of variability for both products during the absorption phase. The GMRs (90% CI) for AMP XR-ODT fed/fasted were within 80-125 percent for dAMP and lAMP AUC 5-last , AUC last , and AUC inf ; C max and AUC 0-5 were slightly lower with food compared with the fasted state, and there was a 2-hour delay in T max from approximately 5 to 7 h. Most common adverse events were nausea (n ¼ 5) and dry mouth (n ¼ 5). Conclusions: AMP XR-ODT displayed a PK profile comparable to XR MAS, and no clinically relevant food effect was observed. AMP XR-ODT has a PK profile consistent with once-daily dosing and an adverse events profile consistent with this class of stimulant medication.
The Journal of Clinical Pharmacology, 2007
The objective of this study was to compare the single-dose pharmacokinetics of multilayer-release... more The objective of this study was to compare the single-dose pharmacokinetics of multilayer-release and immediaterelease methylphenidate in children with attentiondeficit/hyperactivity disorder. Patients 6-to 12-years-old with a DSM-IV diagnosis of attention-deficit/hyperactivity disorder were randomized to receive multilayer-release methylphenidate (qd) or immediate-release methylphenidate (bid) at equivalent doses, with a 14-day washout between treatments. Plasma samples were collected predosing and 1,
Many physicians see pediatric patients whose ADHD warrants pharmacotherapy for an optimal outcome... more Many physicians see pediatric patients whose ADHD warrants pharmacotherapy for an optimal outcome. In selecting an appropriate treatment plan, there are many factors to consider for each individual patient. This review will highlight three considerations: treatment objectives, pharmacotherapy with prodrugs for ADHD, and how to interpret clinical trial data.
Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2010
The Journal of pharmacology and experimental therapeutics, 1987
Six boys with attention-deficit disorder were given single doses (5 or 10 mg) of dl-threo-methylp... more Six boys with attention-deficit disorder were given single doses (5 or 10 mg) of dl-threo-methylphenidate (Ritalin, Ciba-Geigy, Basel, Switzerland). Plasma samples through 8 hr were analyzed by capillary column gas chromatography with electron capture detection. Enantiomers were separated and measured as heptafluorobutyryl-1-prolyl derivatives. The method was sensitive to 0.1 ng of enantiomer per ml of plasma. The plasma levels of d-methylphenidate were at least 5-fold greater than those of the l-enantiomer in the profiles of all six children. Mean areas under the plasma level-time curves were 24.48 +/- 7.62 ng/hr/ml for d-methylphenidate and 3.77 +/- 1.04 ng/hr/ml for l-methylphenidate. There was appreciable intersubject variation in plasma level maxima and times to maximal plasma levels of each enantiomer.
Clinical Pharmacology and Therapeutics, 1992
Nine boys with attention-deficit hyperactivity disorder took part in a study in which d-methylphe... more Nine boys with attention-deficit hyperactivity disorder took part in a study in which d-methylphenidate, I-methylphenidate, dl-methylphenidate, or placebo were administered in a double-blind, four-way, randomized, crossover design. Plasma levels of the isomers of methylphenidate were monitored by means of an enantioselective assay method. The ability of the children to perform tasks that required sustained attention was monitored by a battery of computer tests. There was no evidence of interconversion between the enantiomers in vivo, although the presence of the d-isomer significantly altered the pharmacokinetics of the 1-antipode. The presence of the 1-isomer did not affect the pharmacokinetics of d-methylphenidate. The computer tests revealed a drug-induced improvement in sustained attention that was entirely attributable to the d-enantiomer. There was no evidence to suggest that the effectiveness of d-methylphenidate was in any way compromised by the presence of its antipode. (CLIN PHARMACOL THER
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 1991
Pediatric Drugs, 2003
To evaluate the safety and efficacy of extended-release methylphenidate with a bimodal profile us... more To evaluate the safety and efficacy of extended-release methylphenidate with a bimodal profile using SODAS technology (Ritalin LA ) compared with placebo in children aged 6-14 years with attention deficit hyperactivity disorder (ADHD). This was a multicenter, double-blind, randomized, placebo-controlled, parallel-group study in children meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for ADHD. Following titration and a 1-week placebo washout period, patients were randomized to 2 weeks of double-blind treatment with either Ritalin LA (10-40 mg/day) or placebo. The efficacy assessments used were the Conners' ADHD/DSM-IV Scales for teachers (CADS-T) and for parents (CADS-P), and the Clinical Global Impression-Improvement Scale (CGI-I) completed by the investigator. The primary efficacy variable was the change from baseline (end of placebo washout) to the final rating (end of 2-week double-blind treatment) in the CADS-T Total subscale score. One-hundred-and-sixty-one children were treated and 134 responders were included in the intent-to-treat analysis. Ritalin LA achieved a mean change from baseline (+/- SD) on the CADS-T Total subscale of -10.7 (+/-15.68) compared with 2.8 (+/-10.59) for placebo (p < 0.0001); the effect size on the CADS-T Total score with Ritalin LA was 0.90. Additionally, 69.8% of patients in the Ritalin LA group were rated as much or very much improved on the CGI-I at final assessment compared with 40% of patients in the placebo group (p = 0.0009). The adverse events reported were generally mild or moderate, and were similar in both groups. The results demonstrate that Ritalin LA administered once daily for up to 2 weeks achieved outcomes statistically superior to placebo in children with ADHD.
Journal of the American Academy of Child & Adolescent Psychiatry, 1991
an emergency basis. He stressed the viabi lity of the fetus and that discontinu ation of extern a... more an emergency basis. He stressed the viabi lity of the fetus and that discontinu ation of extern al fetal monitorin g would not afford legal protection. Fetal monitorin g was then resumed , and it continued to indicate mild fetal distress but did not sugges t the need for an immediate cesarea n section. A healthy baby was delivered vaginally several hours later.
Journal of the American Academy of Child & Adolescent Psychiatry, 2004
Objective: Methylphenidate has four optical isomers due to two asymmetries (erythro-threo and dex... more Objective: Methylphenidate has four optical isomers due to two asymmetries (erythro-threo and dextro-levo). The initial commercial formulation eliminated the erythro isomer, but the dextro-levo asymmetry was racemic, with equal amounts of d and l-threo isomers (d,l-MPH). Previous work has suggested that the d-threo isomer methylphenidate (d-MPH) rather than the l-threo isomer (l-MPH) is responsible for the clinical effects in children with attention-deficit/hyperactivity disorder (ADHD). This study compared the efficacy of acute equimolar doses of d-MPH and dl-MPH in reducing ADHD symptoms over an 8-hour period in a laboratory school setting and investigated the relationship of efficacy to plasma levels of MPH. Method: Thirty-two children with ADHD enrolled in this double-blind, placebo-controlled, crossover study, and 31 completed the study. On seven separate occasions separated by at least 6 days, the children received a single morning dose of d-MPH (2.5, 5, or 10 mg), d,l-MPH (5, 10, or 20 mg), or placebo and then were observed in a laboratory classroom setting for 8 hours. At specified intervals, blinded observers rated behavior, and the children performed a computerized math test. The plasma levels of MPH were related to the response to study medication. The safety profiles of the two formulations were compared. Results: For both formulations, the responses to both MPH preparations were dose related, the plasma concentrations of l-MPH were negligible and of d-MPH were indistinguishable, and clinical efficacy was highly correlated with plasma concentrations of d-MPH. The efficacy of the d-isomer was equivalent to the racemic preparation in reducing ADHD symptoms and increasing academic productivity. Conclusions: The efficacy of MPH resides in the d-isomer. The elimination of the l-isomer does not diminish the efficacy of an acute dose of methylphenidate.
Journal of Pharmaceutical Sciences, 1989
0 It has been shown previously that immediaterelease dlfhreernethylphenidate (Ritalin) undergoes ... more 0 It has been shown previously that immediaterelease dlfhreernethylphenidate (Ritalin) undergoes stereoselective disposition in human adults as well as in children with attention deficit-hyperactivity disorder. Although the sustained-release formulation of dl-three methylphenidate (Ritalin-SR) has been demonstrated to be effective in sustaining the attention of the children with attention deficit-hyperactivity disorder, there are no data on plasma levels of methylphenidate after administration of the sustained-release formulation. The purpose of this present investigation was twofold: (1) to determine whether the levels of methylphenidate were sustained for over a time period of 8 h, and (2) to examine enantioselective aspects of the pharmacokinetics following the ingestion of the sustained-release formulation. Six children with attention deficit-hyperactivity disorder were given 20 mg of sustained-release dl-threo methylphenidate. Plasma samples were harvested for a period up to 12 h following ingestion of the drug. The levels of both the enantiomers were sustained for a period of 8 h (the plasma levels of d-methylphenidate were 8to 10-fold higher than those of the 1enantiomer in the profiles of all six children). Mean areas under the plasma level time curves were 132.78 r 92.47 ng*h/mL for OC methylphenidate and 12.73 * 7.37 ng.h/mL for 1-methylphenidate. The values of oral clearance and apparent volume of distribution calculated for 1-enantiomer were higher than the corresponding values for the d-antipode.
Journal of Attention Disorders, 2014
Objective: It has been reported that Oppositional Defiant Disorder (ODD) can be differentiated in... more Objective: It has been reported that Oppositional Defiant Disorder (ODD) can be differentiated into distinct subtypes associated with different outcomes in adulthood. We examined whether ODD is conceptually independent and coherent, and whether ODD and Conduct Disorder (CD) are expressions of the same core deficit. Method: The data come from a sample of 4,380 children for whom SNAP rating scales were available. Parallel analysis was performed on the eight-item ODD diagnostic items and on the SNAP-90 scale. These were factor analyzed and the components were correlated. Results: ODD has one underlying factor, whereas the parent-rated SNAP has nine underlying factors. ODD items grouped together with emotional lability and irritability items, which did not group with CD. Confirmatory factor analysis supported the separation of ODD and CD but not ODD and emotion dysregulation. Conclusion: The expanded ODD factor more likely captures a disorder of emotion regulation, rather than a disruptive behavior disorder. (J. of Att. Dis. 2013; XX(X) 1-XX).
European Child & Adolescent Psychiatry, 2006
To compare the efficacy and safety of two methylphenidate (MPH) formulations--once-daily modified... more To compare the efficacy and safety of two methylphenidate (MPH) formulations--once-daily modified-release MPH (EqXL, Equasym XL) and twice-daily immediate-release methylphenidate (MPH-IR, Ritalin)--and placebo in children with Attention Deficit/Hyperactivity Disorder (ADHD). Children aged 6-12 years on a stable dose of MPH were randomized into a double-blind, three-arm, parallel-group, multi-center study and received 3 weeks of EqXL (20, 40, or 60 mg qd), MPH-IR (10, 20, or 30 mg bid) or placebo. Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher's IOWA Conners' Rating Scale on the last week of treatment (per protocol population). Safety was monitored by adverse events, laboratory parameters, vital signs, physical exam, and a Side Effect Rating Scale. The lower 97.5% confidence interval bound of the difference between MPH groups fell above the non-inferiority margin (-1.5 points) not only during the last week of treatment but during all three treatment weeks. Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks (P < 0.001). All treatments were well tolerated. EqXL given once-daily was non-inferior to MPH-IR given twice-daily. Both treatments were superior to placebo in reducing ADHD symptoms.
Clinical Therapeutics, 2006
C o p y r i g h t © E x c e r p t a M e d i c a , I n c , 2 0 0 6 N o t f o r C o m m e r c i a l... more C o p y r i g h t © E x c e r p t a M e d i c a , I n c , 2 0 0 6 N o t f o r C o m m e r c i a l D i s t r i b u t i o n ABSTRACT Background:
Biological Psychiatry, 1993
1. Biol Psychiatry. 1993 May 15;33(10):755-6. The noncompliance factor in the dexamethasone suppr... more 1. Biol Psychiatry. 1993 May 15;33(10):755-6. The noncompliance factor in the dexamethasone suppression test. Remillard AJ, O'Reilly R, Gorecki DK, Blackshaw SL, Quinn D, Keegan DL. College of Pharmacy, University of Saskatchewan, Saskatoon, Canada. ...
Journal of Child and Adolescent Psychopharmacology, 2007
Patients and Methods: This study was a randomized, double-blind, crossover comparison of once-dai... more Patients and Methods: This study was a randomized, double-blind, crossover comparison of once-daily MLR and twice-daily IR-MPH in home and school settings in children with a
Journal of Child and Adolescent Psychopharmacology, 2007
Objective: The purpose of this study was to evaluate the comparative efficacy and safety of a nov... more Objective: The purpose of this study was to evaluate the comparative efficacy and safety of a novel long-duration multilayer-release (MLR) methylphenidate (MPH) formulation and immediate-release (IR) MPH in attention-deficit/hyperactivity disorder (ADHD) children. Patients and Methods: This study was a randomized, double-blind, crossover comparison of once-daily MLR and twice-daily IR-MPH in home and school settings in children with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of ADHD. Patients completed a 1-week baseline followed by two active medication titration phases. Each phase of treatment was 1-4 weeks of titration with an additional stable dose week. The final dose was based on efficacy and adverse events for each patient. Efficacy measures included Clinical Global Impressions (CGI) and Conners' Parent and Teacher Rating Scales (CPRS and CTRS). The Clinical Assessment of Side Effects (CASE) scale assessed frequency of adverse events. Results: Of the 90 enrolled patients, aged 6.4-17.5 years, 79 (88%) completed the study. Stable daily doses were 32.0 and 32.5 mg for MLR-and IR-MPH, respectively. All efficacy parameters were significantly improved from baseline. A total of 73.2% and 81.0% of patients on MLR-and IR-MPH were rated as "much" or "very much improved" on the CGI. A total of 77.4% and 81.1% of patients were normalized on the CPRS-R and 78.9 and 90.4% of patients were normalized on the CTRS-R for MLR-and IR-MPH, respectively. The mean CASE score was not different from baseline for either treatment.
Journal of the American Academy of Child & Adolescent Psychiatry, 2016
The goals of this session are as follows: 1) to describe the technology underlying amphetamine-ex... more The goals of this session are as follows: 1) to describe the technology underlying amphetamine-extended release-orally disintegrating tablets (AMP XR-ODTs), a novel formulation approved for the treatment of ADHD in patients 6 years of age and older; 2) to assess the effect of food on AMP XR-ODT and compare the rate of absorption and oral bioavailability of AMP XR-ODT with a reference drug [XR-mixed AMP salts (XR MAS)]. Methods: Adult volunteers were enrolled in a single-dose, open-label, threeperiod, three-treatment, randomized crossover pharmacokinetic (PK) study and received an 18.8-mg dose of AMP XR-ODT (fasted or fed) or equivalent dose of XR MAS (fasted). Blood samples were analyzed for dAMP and lAMP (predoseÀ60 h postdose). The following PK parameters were determined: maximum plasma concentration (C max), time to maximum plasma concentration (T max), and area-under-the-concentration-time curve from time zero to the last concentration (AUC last) and to infinity (AUC inf). Early (AUC 0-5) and late (AUC 5-last) exposure also were measured as supportive endpoints. Bioequivalence was established if the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs; AMP XR-ODT/reference drug) for C max and AUCs were within the range of 80 to 125 percent. The effect of food on absorption of AMP XR-ODT was evaluated by comparing C max and AUCs across conditions (fed vs. fasted). Safety also was assessed. Results: A total of 39 participants completed the study. AMP XR-ODT formulation displayed a PK profile similar to XR MAS (fasted). The GMRs (90% CI) for AMP XR-ODT/XR MAS were within 80-125 percent for dAMP and lAMP C max , AUC 5-last , AUC last , and AUC inf ; median T max was approximately 5 h for both products. The 90% CI for AUC 0-5 was slightly below the 80-125 percent interval, possibly because of variability for both products during the absorption phase. The GMRs (90% CI) for AMP XR-ODT fed/fasted were within 80-125 percent for dAMP and lAMP AUC 5-last , AUC last , and AUC inf ; C max and AUC 0-5 were slightly lower with food compared with the fasted state, and there was a 2-hour delay in T max from approximately 5 to 7 h. Most common adverse events were nausea (n ¼ 5) and dry mouth (n ¼ 5). Conclusions: AMP XR-ODT displayed a PK profile comparable to XR MAS, and no clinically relevant food effect was observed. AMP XR-ODT has a PK profile consistent with once-daily dosing and an adverse events profile consistent with this class of stimulant medication.
The Journal of Clinical Pharmacology, 2007
The objective of this study was to compare the single-dose pharmacokinetics of multilayer-release... more The objective of this study was to compare the single-dose pharmacokinetics of multilayer-release and immediaterelease methylphenidate in children with attentiondeficit/hyperactivity disorder. Patients 6-to 12-years-old with a DSM-IV diagnosis of attention-deficit/hyperactivity disorder were randomized to receive multilayer-release methylphenidate (qd) or immediate-release methylphenidate (bid) at equivalent doses, with a 14-day washout between treatments. Plasma samples were collected predosing and 1,
Many physicians see pediatric patients whose ADHD warrants pharmacotherapy for an optimal outcome... more Many physicians see pediatric patients whose ADHD warrants pharmacotherapy for an optimal outcome. In selecting an appropriate treatment plan, there are many factors to consider for each individual patient. This review will highlight three considerations: treatment objectives, pharmacotherapy with prodrugs for ADHD, and how to interpret clinical trial data.
Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2010
The Journal of pharmacology and experimental therapeutics, 1987
Six boys with attention-deficit disorder were given single doses (5 or 10 mg) of dl-threo-methylp... more Six boys with attention-deficit disorder were given single doses (5 or 10 mg) of dl-threo-methylphenidate (Ritalin, Ciba-Geigy, Basel, Switzerland). Plasma samples through 8 hr were analyzed by capillary column gas chromatography with electron capture detection. Enantiomers were separated and measured as heptafluorobutyryl-1-prolyl derivatives. The method was sensitive to 0.1 ng of enantiomer per ml of plasma. The plasma levels of d-methylphenidate were at least 5-fold greater than those of the l-enantiomer in the profiles of all six children. Mean areas under the plasma level-time curves were 24.48 +/- 7.62 ng/hr/ml for d-methylphenidate and 3.77 +/- 1.04 ng/hr/ml for l-methylphenidate. There was appreciable intersubject variation in plasma level maxima and times to maximal plasma levels of each enantiomer.
Clinical Pharmacology and Therapeutics, 1992
Nine boys with attention-deficit hyperactivity disorder took part in a study in which d-methylphe... more Nine boys with attention-deficit hyperactivity disorder took part in a study in which d-methylphenidate, I-methylphenidate, dl-methylphenidate, or placebo were administered in a double-blind, four-way, randomized, crossover design. Plasma levels of the isomers of methylphenidate were monitored by means of an enantioselective assay method. The ability of the children to perform tasks that required sustained attention was monitored by a battery of computer tests. There was no evidence of interconversion between the enantiomers in vivo, although the presence of the d-isomer significantly altered the pharmacokinetics of the 1-antipode. The presence of the 1-isomer did not affect the pharmacokinetics of d-methylphenidate. The computer tests revealed a drug-induced improvement in sustained attention that was entirely attributable to the d-enantiomer. There was no evidence to suggest that the effectiveness of d-methylphenidate was in any way compromised by the presence of its antipode. (CLIN PHARMACOL THER
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 1991
Pediatric Drugs, 2003
To evaluate the safety and efficacy of extended-release methylphenidate with a bimodal profile us... more To evaluate the safety and efficacy of extended-release methylphenidate with a bimodal profile using SODAS technology (Ritalin LA ) compared with placebo in children aged 6-14 years with attention deficit hyperactivity disorder (ADHD). This was a multicenter, double-blind, randomized, placebo-controlled, parallel-group study in children meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for ADHD. Following titration and a 1-week placebo washout period, patients were randomized to 2 weeks of double-blind treatment with either Ritalin LA (10-40 mg/day) or placebo. The efficacy assessments used were the Conners' ADHD/DSM-IV Scales for teachers (CADS-T) and for parents (CADS-P), and the Clinical Global Impression-Improvement Scale (CGI-I) completed by the investigator. The primary efficacy variable was the change from baseline (end of placebo washout) to the final rating (end of 2-week double-blind treatment) in the CADS-T Total subscale score. One-hundred-and-sixty-one children were treated and 134 responders were included in the intent-to-treat analysis. Ritalin LA achieved a mean change from baseline (+/- SD) on the CADS-T Total subscale of -10.7 (+/-15.68) compared with 2.8 (+/-10.59) for placebo (p < 0.0001); the effect size on the CADS-T Total score with Ritalin LA was 0.90. Additionally, 69.8% of patients in the Ritalin LA group were rated as much or very much improved on the CGI-I at final assessment compared with 40% of patients in the placebo group (p = 0.0009). The adverse events reported were generally mild or moderate, and were similar in both groups. The results demonstrate that Ritalin LA administered once daily for up to 2 weeks achieved outcomes statistically superior to placebo in children with ADHD.
Journal of the American Academy of Child & Adolescent Psychiatry, 1991
an emergency basis. He stressed the viabi lity of the fetus and that discontinu ation of extern a... more an emergency basis. He stressed the viabi lity of the fetus and that discontinu ation of extern al fetal monitorin g would not afford legal protection. Fetal monitorin g was then resumed , and it continued to indicate mild fetal distress but did not sugges t the need for an immediate cesarea n section. A healthy baby was delivered vaginally several hours later.
Journal of the American Academy of Child & Adolescent Psychiatry, 2004
Objective: Methylphenidate has four optical isomers due to two asymmetries (erythro-threo and dex... more Objective: Methylphenidate has four optical isomers due to two asymmetries (erythro-threo and dextro-levo). The initial commercial formulation eliminated the erythro isomer, but the dextro-levo asymmetry was racemic, with equal amounts of d and l-threo isomers (d,l-MPH). Previous work has suggested that the d-threo isomer methylphenidate (d-MPH) rather than the l-threo isomer (l-MPH) is responsible for the clinical effects in children with attention-deficit/hyperactivity disorder (ADHD). This study compared the efficacy of acute equimolar doses of d-MPH and dl-MPH in reducing ADHD symptoms over an 8-hour period in a laboratory school setting and investigated the relationship of efficacy to plasma levels of MPH. Method: Thirty-two children with ADHD enrolled in this double-blind, placebo-controlled, crossover study, and 31 completed the study. On seven separate occasions separated by at least 6 days, the children received a single morning dose of d-MPH (2.5, 5, or 10 mg), d,l-MPH (5, 10, or 20 mg), or placebo and then were observed in a laboratory classroom setting for 8 hours. At specified intervals, blinded observers rated behavior, and the children performed a computerized math test. The plasma levels of MPH were related to the response to study medication. The safety profiles of the two formulations were compared. Results: For both formulations, the responses to both MPH preparations were dose related, the plasma concentrations of l-MPH were negligible and of d-MPH were indistinguishable, and clinical efficacy was highly correlated with plasma concentrations of d-MPH. The efficacy of the d-isomer was equivalent to the racemic preparation in reducing ADHD symptoms and increasing academic productivity. Conclusions: The efficacy of MPH resides in the d-isomer. The elimination of the l-isomer does not diminish the efficacy of an acute dose of methylphenidate.
Journal of Pharmaceutical Sciences, 1989
0 It has been shown previously that immediaterelease dlfhreernethylphenidate (Ritalin) undergoes ... more 0 It has been shown previously that immediaterelease dlfhreernethylphenidate (Ritalin) undergoes stereoselective disposition in human adults as well as in children with attention deficit-hyperactivity disorder. Although the sustained-release formulation of dl-three methylphenidate (Ritalin-SR) has been demonstrated to be effective in sustaining the attention of the children with attention deficit-hyperactivity disorder, there are no data on plasma levels of methylphenidate after administration of the sustained-release formulation. The purpose of this present investigation was twofold: (1) to determine whether the levels of methylphenidate were sustained for over a time period of 8 h, and (2) to examine enantioselective aspects of the pharmacokinetics following the ingestion of the sustained-release formulation. Six children with attention deficit-hyperactivity disorder were given 20 mg of sustained-release dl-threo methylphenidate. Plasma samples were harvested for a period up to 12 h following ingestion of the drug. The levels of both the enantiomers were sustained for a period of 8 h (the plasma levels of d-methylphenidate were 8to 10-fold higher than those of the 1enantiomer in the profiles of all six children). Mean areas under the plasma level time curves were 132.78 r 92.47 ng*h/mL for OC methylphenidate and 12.73 * 7.37 ng.h/mL for 1-methylphenidate. The values of oral clearance and apparent volume of distribution calculated for 1-enantiomer were higher than the corresponding values for the d-antipode.
Journal of Attention Disorders, 2014
Objective: It has been reported that Oppositional Defiant Disorder (ODD) can be differentiated in... more Objective: It has been reported that Oppositional Defiant Disorder (ODD) can be differentiated into distinct subtypes associated with different outcomes in adulthood. We examined whether ODD is conceptually independent and coherent, and whether ODD and Conduct Disorder (CD) are expressions of the same core deficit. Method: The data come from a sample of 4,380 children for whom SNAP rating scales were available. Parallel analysis was performed on the eight-item ODD diagnostic items and on the SNAP-90 scale. These were factor analyzed and the components were correlated. Results: ODD has one underlying factor, whereas the parent-rated SNAP has nine underlying factors. ODD items grouped together with emotional lability and irritability items, which did not group with CD. Confirmatory factor analysis supported the separation of ODD and CD but not ODD and emotion dysregulation. Conclusion: The expanded ODD factor more likely captures a disorder of emotion regulation, rather than a disruptive behavior disorder. (J. of Att. Dis. 2013; XX(X) 1-XX).
European Child & Adolescent Psychiatry, 2006
To compare the efficacy and safety of two methylphenidate (MPH) formulations--once-daily modified... more To compare the efficacy and safety of two methylphenidate (MPH) formulations--once-daily modified-release MPH (EqXL, Equasym XL) and twice-daily immediate-release methylphenidate (MPH-IR, Ritalin)--and placebo in children with Attention Deficit/Hyperactivity Disorder (ADHD). Children aged 6-12 years on a stable dose of MPH were randomized into a double-blind, three-arm, parallel-group, multi-center study and received 3 weeks of EqXL (20, 40, or 60 mg qd), MPH-IR (10, 20, or 30 mg bid) or placebo. Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher's IOWA Conners' Rating Scale on the last week of treatment (per protocol population). Safety was monitored by adverse events, laboratory parameters, vital signs, physical exam, and a Side Effect Rating Scale. The lower 97.5% confidence interval bound of the difference between MPH groups fell above the non-inferiority margin (-1.5 points) not only during the last week of treatment but during all three treatment weeks. Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks (P < 0.001). All treatments were well tolerated. EqXL given once-daily was non-inferior to MPH-IR given twice-daily. Both treatments were superior to placebo in reducing ADHD symptoms.
Clinical Therapeutics, 2006
C o p y r i g h t © E x c e r p t a M e d i c a , I n c , 2 0 0 6 N o t f o r C o m m e r c i a l... more C o p y r i g h t © E x c e r p t a M e d i c a , I n c , 2 0 0 6 N o t f o r C o m m e r c i a l D i s t r i b u t i o n ABSTRACT Background:
Biological Psychiatry, 1993
1. Biol Psychiatry. 1993 May 15;33(10):755-6. The noncompliance factor in the dexamethasone suppr... more 1. Biol Psychiatry. 1993 May 15;33(10):755-6. The noncompliance factor in the dexamethasone suppression test. Remillard AJ, O'Reilly R, Gorecki DK, Blackshaw SL, Quinn D, Keegan DL. College of Pharmacy, University of Saskatchewan, Saskatoon, Canada. ...
Journal of Child and Adolescent Psychopharmacology, 2007
Patients and Methods: This study was a randomized, double-blind, crossover comparison of once-dai... more Patients and Methods: This study was a randomized, double-blind, crossover comparison of once-daily MLR and twice-daily IR-MPH in home and school settings in children with a