- Email: [email protected]
hyperactivity disorder
S356
P.l.i Basic and clinical neuroscience - Other
Training alone does not ensure reliable ratings and statistical analysis of ratings from the site cannot establish whether the patient interviews were done appropriately in the study. To overcome the challenge of maintaining a high reliability of assessment during the trial, SES was implemented. This methodology helped in monitoring of recorded patient interviews which ensured compliance with interview techniques, provided an opportunity for SR performance feedback, and a forum for SR and IR calibration of scores. References [1] Andreasen, N.C. (1984). Scale for Assessment of Negative Symptoms (SANS). Department of Psychiatry, University of Iowa. Iowa Ohio. [2] Lipsitz et al (2004). The rater applied performance scale: development and reliability. Psychiatry Research. 127:147-155 [3] Schoemaker, 1. H. (2008, November). Signal Enhancement in Psychiatric Patients. Presented at the Drug Information Association, Buenos Aires, Argentina.
IP.1.i.0381 Long-term safety and efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder R. Lasser1 ., R. Weisler2, J. Young3 , G. Mattingly4, J. Ga05 , L. Adler6 , L. Squires7 . 1 Shire Development Inc., Global Medical Affairs, Wayne, USA; 2Duke University Medical Center, Psychiatry, Durham, USA; 3Rochester Center for Behavioral Medicine, N/A, Rochester Hills, USA; 4 Washington University School of Medicine, N/A, St. Louis, USA; 5 Shire Development Inc., Biostats, Wayne, USA; 6 New York University Langone School of Medicine and New York v.4. Harbor Healthcare Systems, Department of Psychiatry and Child and Adolescent Psychiatry, New York, USA; 7Shire Development Inc., Global Clinical Medicine, Wayne, USA Purpose: Lisdexamfetamine dimesylate (LDX; US tradename, Vyvanse®, Shire US Inc.) is the first prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in the United States (children aged 6-12 and adults) and Canada (children aged 6-12). LDX is a therapeutically inactive molecule. After oral ingestion, LDX is converted to I-lysine and active d-amphetamine, which is responsible for the therapeutic effect. The conversion of LDX to d-amphetamine is unlikely to be affected by gastrointestinal pH and variations in normal gastrointestinal transit times. Preliminary nonclinical data suggest that conversion ofLDX to d-amphetamine may occur in the blood. LDX has been shown to provide consistent medication delivery from patient to patient. The objective of this study was to evaluate the safety and effectiveness of long-term LDX in adults aged 18 to 55 years with ADHD. Methods: This l2-month, open-label, single-arm study emolled adults (18 to 55 years) with ADHD. For most subjects, baseline scores were from a previous 4-week trial. In this study, dosage was optimized to LDX 30, 50, or 70 mg/d over 4 weeks, then continued for 11 months with dosage adjustment allowed. Mean change from baseline (SD) in ADHD Rating Scale (ADHDRS) with adult ADHD prompts and Clinical Global ImpressionsImprovement (CGI-I) were primary and secondary assessments, respectively. Safety assessments included adverse events (AEs), subjective sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI), vital signs (pulse and blood pressure [BPD, and electrocardiograms (ECG). Results: At endpoint (intent-to-treat [ITT]; n = 345), improvement in ADHD-RS total score was 60.7% (26.3; P<.OOOl). For
those who did (n=296) or did not (n=49) previously receive LDX, improvements in ADHD-RS total scores were 61.6% (25.1) and 55.1 % (32.0), respectively. At endpoint, 84.1% ofITT subjects were much/very much improved (CGI-I score ~2); at 12 months, 92.6% (174 of 188 subjects) were much/very much improved. At last dose, 17.5%, 32.4%, and 50.1 % of subjects received 30, 50, or 70mg/d, respectively. Of 158 subjects (45.3%) who discontinued from the study, 28 (8.0%) discontinued due to AEs. Similar percentages of treatment-emergent AEs (TEAEs) were reported in subjects who received LDX in the prior study (88.2%) and subjects who were LDX-naive (84.6%). TEAEs included upper respiratory tract infection (21.8%), insonmia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%), with most being mild to moderate in severity. The overall mean (SD) PSQI total score decrease from baseline to endpoint of -1.3 (2.8) was significant (P<.OOOI). At endpoint, small, statistically significant increases in mean (SD) pulse (3.2 [11.6] bpm), systolic BP (3.1 [10.7] mIll Hg), and diastolic BP (1.3 [7.6] mIll Hg) were observed. Conclusions: Long-term treatment with LDX resulted in sustained improvement in ADHD symptoms. In adults, LDX was generally well tolerated with a safety profile consistent with longacting stimulant use; most AEs were mild to moderate in severity. Sleep quality was not adversely affected with LDX in most subjects and global PSQI decreased overall, indicating improvement. Changes in pulse and BP, while statistically significant, were generally small and consistent with known effects of stimulants. Supported by funding from Shire Development Inc.
1P.1.i.0391 Differences in melatonin therapy response in elderly patients with various ages at the onset of insomnia S. Nastase 1 " L. Nastase 2 . 1 Clinical Hospital of Psychiatry "AI. Obregia ",9th Adult Psychiatric Department, Bucharest, Romania; 2 Clinical Hospital "Panait Sarbu ", Neonatology, Bucharest, Romania Biological aging is often associated with insonmia. The link among melatonin levels, pineal function, and insonmia is strengthened by epidemiologic and chronobiological evidence [1]. Purpose: We examined whether sleep disorders in old age responds particularly to the treatment with melatonin, in comparison with the adult patients with insonmia and whether melatonin has an influence on age-related insonmia, in elderly people with late onset of insonmia. Method: We ran an open label study on 64 subjects. None suffered from depression, dementia, sleep apnoea or restless legs syndrome. Data such age, sex, and the age at the onset of insonmia were collected. The study population comprised two groups: one group with patients with insonmia whose ages were over 65 years (31 subjects) and the other group with young adults, with ages between 20 and 39 years (33 subjects). We have divided the elderly group in two subgroups: the first with a long history of insonmia (16 subjects with the onset ofinsonmia before reaching 50 years) and the second with a late onset of insonmia (after 50 years of age, 15 subjects). The Athens Insonmia Scale 5-item version (AIS-5) was administered to the two groups before and after the treatment with melatonin. The AIS is a self-assessment psychometric instrument designed for evaluating sleep modifications based on the ICD-lO criteria. It consists of eight items: the first five pertain to sleep induction, awakenings during the night, final awakening,
P.l.i Basic and clinical neuroscience - Other
Training alone does not ensure reliable ratings and statistical analysis of ratings from the site cannot establish whether the patient interviews were done appropriately in the study. To overcome the challenge of maintaining a high reliability of assessment during the trial, SES was implemented. This methodology helped in monitoring of recorded patient interviews which ensured compliance with interview techniques, provided an opportunity for SR performance feedback, and a forum for SR and IR calibration of scores. References [1] Andreasen, N.C. (1984). Scale for Assessment of Negative Symptoms (SANS). Department of Psychiatry, University of Iowa. Iowa Ohio. [2] Lipsitz et al (2004). The rater applied performance scale: development and reliability. Psychiatry Research. 127:147-155 [3] Schoemaker, 1. H. (2008, November). Signal Enhancement in Psychiatric Patients. Presented at the Drug Information Association, Buenos Aires, Argentina.
IP.1.i.0381 Long-term safety and efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder R. Lasser1 ., R. Weisler2, J. Young3 , G. Mattingly4, J. Ga05 , L. Adler6 , L. Squires7 . 1 Shire Development Inc., Global Medical Affairs, Wayne, USA; 2Duke University Medical Center, Psychiatry, Durham, USA; 3Rochester Center for Behavioral Medicine, N/A, Rochester Hills, USA; 4 Washington University School of Medicine, N/A, St. Louis, USA; 5 Shire Development Inc., Biostats, Wayne, USA; 6 New York University Langone School of Medicine and New York v.4. Harbor Healthcare Systems, Department of Psychiatry and Child and Adolescent Psychiatry, New York, USA; 7Shire Development Inc., Global Clinical Medicine, Wayne, USA Purpose: Lisdexamfetamine dimesylate (LDX; US tradename, Vyvanse®, Shire US Inc.) is the first prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in the United States (children aged 6-12 and adults) and Canada (children aged 6-12). LDX is a therapeutically inactive molecule. After oral ingestion, LDX is converted to I-lysine and active d-amphetamine, which is responsible for the therapeutic effect. The conversion of LDX to d-amphetamine is unlikely to be affected by gastrointestinal pH and variations in normal gastrointestinal transit times. Preliminary nonclinical data suggest that conversion ofLDX to d-amphetamine may occur in the blood. LDX has been shown to provide consistent medication delivery from patient to patient. The objective of this study was to evaluate the safety and effectiveness of long-term LDX in adults aged 18 to 55 years with ADHD. Methods: This l2-month, open-label, single-arm study emolled adults (18 to 55 years) with ADHD. For most subjects, baseline scores were from a previous 4-week trial. In this study, dosage was optimized to LDX 30, 50, or 70 mg/d over 4 weeks, then continued for 11 months with dosage adjustment allowed. Mean change from baseline (SD) in ADHD Rating Scale (ADHDRS) with adult ADHD prompts and Clinical Global ImpressionsImprovement (CGI-I) were primary and secondary assessments, respectively. Safety assessments included adverse events (AEs), subjective sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI), vital signs (pulse and blood pressure [BPD, and electrocardiograms (ECG). Results: At endpoint (intent-to-treat [ITT]; n = 345), improvement in ADHD-RS total score was 60.7% (26.3; P<.OOOl). For
those who did (n=296) or did not (n=49) previously receive LDX, improvements in ADHD-RS total scores were 61.6% (25.1) and 55.1 % (32.0), respectively. At endpoint, 84.1% ofITT subjects were much/very much improved (CGI-I score ~2); at 12 months, 92.6% (174 of 188 subjects) were much/very much improved. At last dose, 17.5%, 32.4%, and 50.1 % of subjects received 30, 50, or 70mg/d, respectively. Of 158 subjects (45.3%) who discontinued from the study, 28 (8.0%) discontinued due to AEs. Similar percentages of treatment-emergent AEs (TEAEs) were reported in subjects who received LDX in the prior study (88.2%) and subjects who were LDX-naive (84.6%). TEAEs included upper respiratory tract infection (21.8%), insonmia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%), with most being mild to moderate in severity. The overall mean (SD) PSQI total score decrease from baseline to endpoint of -1.3 (2.8) was significant (P<.OOOI). At endpoint, small, statistically significant increases in mean (SD) pulse (3.2 [11.6] bpm), systolic BP (3.1 [10.7] mIll Hg), and diastolic BP (1.3 [7.6] mIll Hg) were observed. Conclusions: Long-term treatment with LDX resulted in sustained improvement in ADHD symptoms. In adults, LDX was generally well tolerated with a safety profile consistent with longacting stimulant use; most AEs were mild to moderate in severity. Sleep quality was not adversely affected with LDX in most subjects and global PSQI decreased overall, indicating improvement. Changes in pulse and BP, while statistically significant, were generally small and consistent with known effects of stimulants. Supported by funding from Shire Development Inc.
1P.1.i.0391 Differences in melatonin therapy response in elderly patients with various ages at the onset of insomnia S. Nastase 1 " L. Nastase 2 . 1 Clinical Hospital of Psychiatry "AI. Obregia ",9th Adult Psychiatric Department, Bucharest, Romania; 2 Clinical Hospital "Panait Sarbu ", Neonatology, Bucharest, Romania Biological aging is often associated with insonmia. The link among melatonin levels, pineal function, and insonmia is strengthened by epidemiologic and chronobiological evidence [1]. Purpose: We examined whether sleep disorders in old age responds particularly to the treatment with melatonin, in comparison with the adult patients with insonmia and whether melatonin has an influence on age-related insonmia, in elderly people with late onset of insonmia. Method: We ran an open label study on 64 subjects. None suffered from depression, dementia, sleep apnoea or restless legs syndrome. Data such age, sex, and the age at the onset of insonmia were collected. The study population comprised two groups: one group with patients with insonmia whose ages were over 65 years (31 subjects) and the other group with young adults, with ages between 20 and 39 years (33 subjects). We have divided the elderly group in two subgroups: the first with a long history of insonmia (16 subjects with the onset ofinsonmia before reaching 50 years) and the second with a late onset of insonmia (after 50 years of age, 15 subjects). The Athens Insonmia Scale 5-item version (AIS-5) was administered to the two groups before and after the treatment with melatonin. The AIS is a self-assessment psychometric instrument designed for evaluating sleep modifications based on the ICD-lO criteria. It consists of eight items: the first five pertain to sleep induction, awakenings during the night, final awakening,