- Email: [email protected]
HYPERACTIVITY DISORDER IMPULSIVITY SYMPTOMS IN CHILDREN
NEW RESEARCH POSTERS 6.50 – 6.52
Objectives: Two studies sought to compare the pharmacokinetics of PRC063 with immediate-release methylphenidate (IR MPH): Study A a single-dose crossover study in adolescents with ADHD; and Study B a 5-day steady-state crossover study in healthy adults. Methods: Study A involved adolescents (12-17 years) with a DSM-5 diagnosis of ADHD and receiving a stable dose of MPH. Subjects took a single daily dose of PRC-063 or IR MPH (tid) that was approximate to their pre-study dose. Plasma samples were collected prior to dosing and at 0.5 through to 30 h post-dose. Study B involved healthy adults 18 years of age or older. Subjects received either 100mg of PRC-063 or 60mg of IR MPH (20mg tid) for 5 days. Plasma samples were collected prior to dosing at Day 1, 3, 4 and 5, and on Day 5 at 0.5 through to 36 hours post-dose. Results: Study A enrolled 17 patients (3 female, 14 male, age 14.01.0 yrs). The mean daily dose was 62.9 mg/day of PRC-063 and 54.7 mg/day of IR MPH. For d-methylphenidate non-dose-normalised data, the ratios of leastsquares means of PRC-063:IR MPH for ln-transformed AUC0-t, AUC0-inf and Cmax were 96.66%, 100.76% and 67.06%, respectively. Residual levels of MPH at 24 h post dose were 3.28 ng/mL for PRC-063 and 0.53 ng/mL for IR MPH. Study B enrolled 21 subjects (9 female, 12 male, age 328 yrs). There were two distinct peak plasma levels of MPH for PRC-063 (1.5 and 12 h post dose) and three for IR MPH (2, 5.5 and 10 h post dose). Fluctuation Index was 131.531.9% for PRC-063 and 243.5334.0% for IR MPH. For d-methylphenidate dose-normalised data, the ratios of least-squares means of PRC063:IR MPH for AUC0-24, Cmax and Cmin were 88.57 percent, 59.35 percent and 274.15 percent, respectively. Steady-state was achieved for PRC-063 by Day 3. No new safety signals were identified in these studies. Conclusions: In both studies, the extent of absorption was comparable between PRC-063 administered as a single dose and IR MPH administered three times; however, the rate of absorption was lower for PRC-063. No evidence of unusually rapid release was observed compared to IR MPH. PRC063 provides a once-daily alternative to tid administration of MPH with less peak to trough fluctuation and higher plasma levels from hour 12 to the end of the day.
ADHD PKS PPC Supported by Purdue Pharma http://dx.doi.org/10.1016/j.jaac.2016.09.368
6.50 VALIDITY OF PROPOSED DSM-5 ATTENTIONDEFICIT/HYPERACTIVITY DISORDER IMPULSIVITY SYMPTOMS IN CHILDREN
€ €l Unsel Gu Bolat, MD, Department of Child and Adolescent Psychiatry, Ege University, Department of Child and Adolescent Psychiatry, Faculty of Medicine, Ege University, Izmir, Turkey, Izmir, Turkey; Eyup Sabri Ercan, MD; Giovanni Salum; € € Oznur Bilac¸; Rafael Massuti; Taciser Uysal Ozaslan; Hilmi Bolat; Luis A. Rohde, MD, PhD Objectives: The APA working group on ADHD proposed the inclusion of four new impulsivity symptoms. However, they were not included in DSM-5 because of the lack of sufficient evidence. The aim of this study is to investigate the performance of the proposed four ADHD impulsivity symptoms, with respect to the following: 1) ADHD factor structure; 2) performance in predicting clinical impairment; 3) specificity for ADHD diagnosis; and 4) best symptomatic threshold to predict clinical impairment. Methods: The sample group included 416 children from 12 schools: 31 subjects with ADHD according to both DSM-IV and proposed DSM-5; 20 subjects with ADHD, according to just one diagnostic system; and 365 control subjects. Diagnoses were derived using semistructured interviews and ADHD rating scales. Parent gave their written informed consents. The Ege University Ethics Committee approved the study protocol. Results: For both parents and teachers, according to both DSM-IV and DSM-5 solutions, the bifactor model with a general factor and three specific factors had the best fit to the data compared with the other models. Results from confirmatory factor analysis indicate that addition of the four new impulsivity items provided a similar factor structure compared with models including only 18 items. Regression analyses showed that only one of the new impulsivity symptoms (impatient) was part of the list of best predictors of
S220
www.jaacap.org
impairment. None of the four new impulsivity items was associated specifically with ADHD diagnosis. The best cutoff point in the hyperactivity/impulsivity dimension for predicting impairment did not change significantly. Conclusions: Overall, our findings suggest that the determination on ways to best capture impulsivity dimension as part of the ADHD construct needs more investigation. The inclusion of the proposed four impulsivity symptoms seems to add some value in terms of capturing specific impairment and to perform somewhat better than current items, with respect to the factor structure.
ADHD DIAG IMP http://dx.doi.org/10.1016/j.jaac.2016.09.369
6.51 MEDICATION ADHERENCE AND USE OF ILLICIT SUBSTANCES IN PEDIATRIC AND YOUNG ADULT PATIENTS PRESCRIBED STIMULANT MEDICATIONS INDICATED FOR ATTENTIONDEFICIT/HYPERACTIVITY DISORDER Mancia Ko, PharmD, Ameritox Ltd., 300 E. Lombard St., Suite 1610, Baltimore, MD 21202; Patricia Woster, PharmD, Ameritox Ltd., 300 E. Lombard St., Suite 1610, Baltimore, MD, 21202; Thomas Smith, MD Objectives: This study aimed to identify potential nonadherence among pediatric, adolescent, and young adult patients prescribed attention-deficit/ hyperactivity disorder (ADHD) stimulant medications and assess the differences in illicit substance and/or nonprescribed medication use in patients testing positive versus negative for the ADHD medication. Methods: Urine samples submitted to the laboratory between July 2014 and November 2015 from patients 6 to 25 years old, inclusive, who were documented on the laboratory requisition to have been prescribed an amphetamine or methylphenidate medication for the treatment of ADHD were included in the analysis. The first urine sample obtained from each patient was analyzed for the presence of the prescribed ADHD medication, illicit substances (marijuana metabolite [THC] and cocaine metabolite [benzoylecgonine]), and select nonprescribed opioid or benzodiazepine medications. Results: Samples were analyzed from 2436 patients; 64.2 percent of patients were male and the meanSD age was 14.35.4 years. Overall, 32.6 percent of patients tested negative for their prescribed ADHD medication. Patients aged 6 to 10 years had the lowest rate of negative test results (23.2 percent) and patients aged 18 to 21 years had the highest rate (46.0%; adjusted odds ratio [aOR], 2.91; 95% confidence interval [CI], 2.15-3.95). Illicit substances, primarily THC, was rarely detected for patients under age 14, but were detected in 11.8 percent, 21.3 percent, and 17.9 percent of patients 14 to 17, 18 to 21, and 22 to 25 years, respectively. Detection of nonprescribed opioid medications was rare in patients <18 years old, but were found in 7.8 percent and 14.7 percent of patients 18 to 21 and 22 to 25 years, respectively. Patients who tested negative for prescribed ADHD medication were significantly more likely than patients who tested positive to have THC detected in the urine sample (18.1% vs 6.5%; aOR, 2.28; 95% CI, 1.64-3.16). Conclusions: Urine drug monitoring in patients prescribed stimulant ADHD medication can be of value both for evaluating adherence to ADHD therapy and identifying the inappropriate use of illicit substances and/or nonprescribed medications. The data suggest that potential nonadherence to prescribed stimulant ADHD therapy is associated with marijuana use and that detection of marijuana in children as young as 14 to 17 years is not uncommon.
ADHD Supported by Ingenuity Health, a service of Ameritox Ltd. http://dx.doi.org/10.1016/j.jaac.2016.09.370
6.52 FACTORS RELATED TO DROPOUT FROM METHYLPHENIDATE OF ADOLESCENTS WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
nchez, MD, Psychiatry, Universidad Nacional Diana Guızar-Sa Autonoma de Mexico, Circuito Interior Universitario y Cerro del Agua, Mexico City, 04510, Mexico; Lino Palacios Cruz, PhD; ~ a, MD Francisco R. De la Pen
J OURNAL
OF THE
AMERICAN ACADEMY OF CHILD & ADOLESCENT P SYCHIATRY VOLUME 55 NUMBER 10S OCTOBER 2016
Objectives: Two studies sought to compare the pharmacokinetics of PRC063 with immediate-release methylphenidate (IR MPH): Study A a single-dose crossover study in adolescents with ADHD; and Study B a 5-day steady-state crossover study in healthy adults. Methods: Study A involved adolescents (12-17 years) with a DSM-5 diagnosis of ADHD and receiving a stable dose of MPH. Subjects took a single daily dose of PRC-063 or IR MPH (tid) that was approximate to their pre-study dose. Plasma samples were collected prior to dosing and at 0.5 through to 30 h post-dose. Study B involved healthy adults 18 years of age or older. Subjects received either 100mg of PRC-063 or 60mg of IR MPH (20mg tid) for 5 days. Plasma samples were collected prior to dosing at Day 1, 3, 4 and 5, and on Day 5 at 0.5 through to 36 hours post-dose. Results: Study A enrolled 17 patients (3 female, 14 male, age 14.01.0 yrs). The mean daily dose was 62.9 mg/day of PRC-063 and 54.7 mg/day of IR MPH. For d-methylphenidate non-dose-normalised data, the ratios of leastsquares means of PRC-063:IR MPH for ln-transformed AUC0-t, AUC0-inf and Cmax were 96.66%, 100.76% and 67.06%, respectively. Residual levels of MPH at 24 h post dose were 3.28 ng/mL for PRC-063 and 0.53 ng/mL for IR MPH. Study B enrolled 21 subjects (9 female, 12 male, age 328 yrs). There were two distinct peak plasma levels of MPH for PRC-063 (1.5 and 12 h post dose) and three for IR MPH (2, 5.5 and 10 h post dose). Fluctuation Index was 131.531.9% for PRC-063 and 243.5334.0% for IR MPH. For d-methylphenidate dose-normalised data, the ratios of least-squares means of PRC063:IR MPH for AUC0-24, Cmax and Cmin were 88.57 percent, 59.35 percent and 274.15 percent, respectively. Steady-state was achieved for PRC-063 by Day 3. No new safety signals were identified in these studies. Conclusions: In both studies, the extent of absorption was comparable between PRC-063 administered as a single dose and IR MPH administered three times; however, the rate of absorption was lower for PRC-063. No evidence of unusually rapid release was observed compared to IR MPH. PRC063 provides a once-daily alternative to tid administration of MPH with less peak to trough fluctuation and higher plasma levels from hour 12 to the end of the day.
ADHD PKS PPC Supported by Purdue Pharma http://dx.doi.org/10.1016/j.jaac.2016.09.368
6.50 VALIDITY OF PROPOSED DSM-5 ATTENTIONDEFICIT/HYPERACTIVITY DISORDER IMPULSIVITY SYMPTOMS IN CHILDREN
€ €l Unsel Gu Bolat, MD, Department of Child and Adolescent Psychiatry, Ege University, Department of Child and Adolescent Psychiatry, Faculty of Medicine, Ege University, Izmir, Turkey, Izmir, Turkey; Eyup Sabri Ercan, MD; Giovanni Salum; € € Oznur Bilac¸; Rafael Massuti; Taciser Uysal Ozaslan; Hilmi Bolat; Luis A. Rohde, MD, PhD Objectives: The APA working group on ADHD proposed the inclusion of four new impulsivity symptoms. However, they were not included in DSM-5 because of the lack of sufficient evidence. The aim of this study is to investigate the performance of the proposed four ADHD impulsivity symptoms, with respect to the following: 1) ADHD factor structure; 2) performance in predicting clinical impairment; 3) specificity for ADHD diagnosis; and 4) best symptomatic threshold to predict clinical impairment. Methods: The sample group included 416 children from 12 schools: 31 subjects with ADHD according to both DSM-IV and proposed DSM-5; 20 subjects with ADHD, according to just one diagnostic system; and 365 control subjects. Diagnoses were derived using semistructured interviews and ADHD rating scales. Parent gave their written informed consents. The Ege University Ethics Committee approved the study protocol. Results: For both parents and teachers, according to both DSM-IV and DSM-5 solutions, the bifactor model with a general factor and three specific factors had the best fit to the data compared with the other models. Results from confirmatory factor analysis indicate that addition of the four new impulsivity items provided a similar factor structure compared with models including only 18 items. Regression analyses showed that only one of the new impulsivity symptoms (impatient) was part of the list of best predictors of
S220
www.jaacap.org
impairment. None of the four new impulsivity items was associated specifically with ADHD diagnosis. The best cutoff point in the hyperactivity/impulsivity dimension for predicting impairment did not change significantly. Conclusions: Overall, our findings suggest that the determination on ways to best capture impulsivity dimension as part of the ADHD construct needs more investigation. The inclusion of the proposed four impulsivity symptoms seems to add some value in terms of capturing specific impairment and to perform somewhat better than current items, with respect to the factor structure.
ADHD DIAG IMP http://dx.doi.org/10.1016/j.jaac.2016.09.369
6.51 MEDICATION ADHERENCE AND USE OF ILLICIT SUBSTANCES IN PEDIATRIC AND YOUNG ADULT PATIENTS PRESCRIBED STIMULANT MEDICATIONS INDICATED FOR ATTENTIONDEFICIT/HYPERACTIVITY DISORDER Mancia Ko, PharmD, Ameritox Ltd., 300 E. Lombard St., Suite 1610, Baltimore, MD 21202; Patricia Woster, PharmD, Ameritox Ltd., 300 E. Lombard St., Suite 1610, Baltimore, MD, 21202; Thomas Smith, MD Objectives: This study aimed to identify potential nonadherence among pediatric, adolescent, and young adult patients prescribed attention-deficit/ hyperactivity disorder (ADHD) stimulant medications and assess the differences in illicit substance and/or nonprescribed medication use in patients testing positive versus negative for the ADHD medication. Methods: Urine samples submitted to the laboratory between July 2014 and November 2015 from patients 6 to 25 years old, inclusive, who were documented on the laboratory requisition to have been prescribed an amphetamine or methylphenidate medication for the treatment of ADHD were included in the analysis. The first urine sample obtained from each patient was analyzed for the presence of the prescribed ADHD medication, illicit substances (marijuana metabolite [THC] and cocaine metabolite [benzoylecgonine]), and select nonprescribed opioid or benzodiazepine medications. Results: Samples were analyzed from 2436 patients; 64.2 percent of patients were male and the meanSD age was 14.35.4 years. Overall, 32.6 percent of patients tested negative for their prescribed ADHD medication. Patients aged 6 to 10 years had the lowest rate of negative test results (23.2 percent) and patients aged 18 to 21 years had the highest rate (46.0%; adjusted odds ratio [aOR], 2.91; 95% confidence interval [CI], 2.15-3.95). Illicit substances, primarily THC, was rarely detected for patients under age 14, but were detected in 11.8 percent, 21.3 percent, and 17.9 percent of patients 14 to 17, 18 to 21, and 22 to 25 years, respectively. Detection of nonprescribed opioid medications was rare in patients <18 years old, but were found in 7.8 percent and 14.7 percent of patients 18 to 21 and 22 to 25 years, respectively. Patients who tested negative for prescribed ADHD medication were significantly more likely than patients who tested positive to have THC detected in the urine sample (18.1% vs 6.5%; aOR, 2.28; 95% CI, 1.64-3.16). Conclusions: Urine drug monitoring in patients prescribed stimulant ADHD medication can be of value both for evaluating adherence to ADHD therapy and identifying the inappropriate use of illicit substances and/or nonprescribed medications. The data suggest that potential nonadherence to prescribed stimulant ADHD therapy is associated with marijuana use and that detection of marijuana in children as young as 14 to 17 years is not uncommon.
ADHD Supported by Ingenuity Health, a service of Ameritox Ltd. http://dx.doi.org/10.1016/j.jaac.2016.09.370
6.52 FACTORS RELATED TO DROPOUT FROM METHYLPHENIDATE OF ADOLESCENTS WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
nchez, MD, Psychiatry, Universidad Nacional Diana Guızar-Sa Autonoma de Mexico, Circuito Interior Universitario y Cerro del Agua, Mexico City, 04510, Mexico; Lino Palacios Cruz, PhD; ~ a, MD Francisco R. De la Pen
J OURNAL
OF THE
AMERICAN ACADEMY OF CHILD & ADOLESCENT P SYCHIATRY VOLUME 55 NUMBER 10S OCTOBER 2016