Efficacy of Lemborexant in Adults ≥ 65 Years of Age with Insomnia Disorder.

BACKGROUND: Pharmacologic treatments are available to treat insomnia, a common and burdensome sleep disorder, but may be contraindicated in older adults who are prone to side effects from sleep-promoting drugs. These analyses of sleep diary data from Study E2006-G000-303 (Study 303) investigated the benefits of lemborexant 5 mg (LEM5) and 10 mg (LEM10) in the subgroup age ≥ 65 years with insomnia. METHOD: Study 303, a 12-month, double-blind study of LEM5 and LEM10 in adults (age ≥ 18 years) with insomnia disorder (sleep onset and/or maintenance difficulties) assessed subject-reported (subjective) sleep-onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), and total sleep time (sTST). Morning sleepiness/alertness, insomnia severity (Insomnia Severity Index [ISI]), fatigue (Fatigue Severity Scale [FSS]), perceptions of sleep-related medication effects (Patient Global Impression-Insomnia [PGI-I] questionnaire), and safety were also evaluated. RESULTS: In this subgroup of older adults (≥ 65 years; n = 262), there were significantly larger changes from baseline for sSOL, sSE, sTST, and sWASO with LEM5 and LEM10 versus placebo through month 6 (except sWASO month 1), indicating improvement; these improvements were sustained through month 12. Subject-reported increases in morning alertness were significantly greater with one or both LEM doses versus placebo through month 6 and sustained through month 12. There were significantly larger ISI total and daytime functioning score decreases (improvement) from baseline with LEM versus placebo at months 1, 3, and 6 (total score: both doses; daytime functioning: LEM5 month 1 and both doses months 3 and 6) and decreases from baseline FSS at months 1 and 3 (LEM5) and month 6 (both doses), sustained to month 12. Compared with placebo, more subjects reported that LEM (both doses) positively impacted ability to sleep, time to fall asleep, and TST through month 6, sustained to month 12, with no rebound after drug withdrawal. LEM was well tolerated to month 12; mild somnolence was the most common treatment-emergent adverse event. CONCLUSIONS: Improvements in subject-reported efficacy in LEM-treated adults age ≥ 65 years with insomnia were observed as early as the first week of treatment and sustained through end of month 12. LEM was well tolerated. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02952820: E2006-G000-303; Study 303; SUNRISE-2 (First posted: October 2016); EudraCT 2015-001463-39 (First posted: November 2016).

Insomnia is a common sleep disorder associated with significant difficulties, particularly in older adults. Although there are many drug treatments available, some are associated with the important risk of side effects and may not adequately treat sleep maintenance (ability to stay asleep), which is a frequent sleep complaint in older people. Lemborexant has been approved in multiple countries for the treatment of adults with insomnia based on studies that show lemborexant improved adults' ability to fall asleep and stay asleep and is well tolerated. To examine the long-term benefit of lemborexant, we investigated subject-reported benefits and safety of lemborexant in older (≥ 65 years) adults who participated in a 1-year study. The results showed that within the first few days of taking lemborexant, and lasting through 12 months of treatment, nightly lemborexant improved nighttime sleep (that is, it reduced the time it took to fall asleep, reduced the time awake during the night, and increased total sleep time) more than placebo. Morning alertness improved more in older adults who took lemborexant compared with placebo. In addition, those who took lemborexant also reported that their insomnia symptoms were less severe and they had less fatigue compared with placebo. Lemborexant was well tolerated in older adults. These results suggest that lemborexant may be a good option for older adults with insomnia disorder.

A Post-Hoc Analysis of Emotional Lability With Delayed-Release/Extended-Release Methylphenidate in Children Aged 6 to 12 Years of Age Participating in Two Phase 3 Clinical Trials.

OBJECTIVE: DR/ER-MPH (formerly HLD200) is an evening-dosed delayed-release and extended-release methylphenidate approved for the treatment of ADHD in patients ≥6 years. Post hoc analyses of two pivotal Phase 3 trials: HLD200-107 (NCT02493777) and HLD200-108 (NCT02520388) evaluated emotional lability (EL) with DR/ER-MPH treatment. METHODS: Differences in Conners Global Index-Parent (CGI-P) EL subscale scores and age- and gender-adjusted T-scores over an open-label titration phase (HLD200-107) and between treatment and placebo groups at endpoint (HLD200-108) were evaluated. RESULTS: In HLD200-107 (N = 117) mean CGI-P EL subscale scores improved from 5.3 to 1.3 (p < .0001) after 6 weeks; in HLD200-108 significant improvements were observed in the treatment group (n = 81) versus placebo (n = 80; 3.11 vs. 4.08; p = .0053). T-scores showed an improvement with DR/ER-MPH treatment in both trials. Few emotional adverse events (AEs) were reported. CONCLUSION: DR/ER-MPH treatment resulted in statistically significant improvements in EL to the level of non-ADHD peers as contextualized by T-scores.

A Long-Term, Open-Label Safety and Tolerability Study of Lisdexamfetamine Dimesylate in Children Aged 4-5 Years with Attention-Deficit/Hyperactivity Disorder.

Objective: To evaluate the long-term safety and tolerability of lisdexamfetamine dimesylate (LDX) in preschool-aged children (4-5 years of age inclusive) diagnosed with attention-deficit/hyperactivity disorder (ADHD). Methods: This phase 3 open-label study (ClinicalTrials.gov registry: NCT02466386) enrolled children aged 4-5 years meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for a primary ADHD diagnosis and having baseline ADHD Rating Scale-IV Preschool version total scores (ADHD-RS-IV-PS-TS) ≥24 for girls or ≥28 for boys and baseline Clinical Global Impressions-Severity scores ≥4. Participants were directly enrolled or enrolled after completing one of two antecedent short-term LDX studies. Over 52 weeks of treatment, participants received once-daily dose-optimized LDX (5-30 mg). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital sign changes. Clinical outcomes included ADHD-RS-IV-PS-TS changes from baseline. Results: Among 113 participants in the safety set, optimized LDX dose was 5, 10, 15, 20, and 30 mg in 1 (0.9%), 12 (10.6%), 21 (18.6%), 26 (23.0%), and 53 (46.9%) participants, respectively. Of the safety set, 69 participants (61.1%) completed the study. TEAEs were reported in 76.1% of participants; no serious TEAEs were reported. Only one type of TEAE was reported in >10% of participants (decreased appetite, 15.9%). Mean ± standard deviation (SD) changes in vital signs and body weight from baseline to week 52/or early termination (ET; n = 101) were 1.9 ± 7.73 mmHg for systolic blood pressure, 3.1 ± 7.58 mmHg for diastolic blood pressure, 4.7 ± 11.00 bpm for pulse, and 0.6 ± 1.38 kg for body weight. Over the course of the study, mean ± SD change in ADHD-RS-IV-PS-TS from baseline to week 52/ET was -24.2 ± 13.34 (n = 87). Conclusions: In this long-term 52-week study of children aged 4-5 years with ADHD, dose-optimized LDX (5-30 mg) was well tolerated and associated with reductions from baseline in ADHD symptoms.

A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of AR19, a Manipulation-Resistant Formulation of Amphetamine Sulfate, in Adults With Attention-Deficit/Hyperactivity Disorder.

Objective: To assess the efficacy and safety of AR19 in the treatment of attention-deficit/hyperactivity disorder (ADHD) diagnosed by DSM-5 criteria in adults from 18 through 55 years of age. AR19 is a pellets-in-capsule, immediate-release amphetamine sulfate investigational formulation with physical and chemical barriers designed to resist manipulation to deter snorting, smoking, and intravenous injection.Methods: This randomized, double-blind, placebo-controlled, fixed-dose, forced titration, multicenter trial investigated the safety and efficacy of AR19 from September 2018 to April 2019. Study participants were randomized and titrated to 20 mg or 40 mg AR19 daily or placebo. Study medication was dosed once in the morning and again 4 to 6 hours later for a period of 5 weeks. The primary efficacy measure was the total score on the Adult ADHD Investigator Symptom Rating Scale (AISRS).Results: Participants (N = 320) were randomized and received at least 1 dose of study medication. Demographics and baseline characteristics were similar across treatment groups. The least squares mean treatment differences versus placebo (97.5% CI) were -7.2 (-11.3 to -3.1) for the AR19 20-mg group and -7.3 (-11.4 to -3.2) for the AR19 40-mg group (each P < .001). The most common treatment-emergent adverse events occurring in participants in the AR19 treatment groups were insomnia, dry mouth, decreased appetite, palpitations, headache, and tachycardia and are consistent with the known safety profile of amphetamine sulfate.Conclusions: AR19 demonstrated efficacy on all endpoints and was generally well tolerated, supporting the efficacy and safety of AR19 20 mg and 40 mg in adults with ADHD.Trial Registration: ClinicalTrials.gov Identifier: NCT03659929.

A Phase 3, Randomized Double-Blind Study of the Efficacy and Safety of Low-Dose SHP465 Mixed Amphetamine Salts Extended-Release in Children with Attention-Deficit/Hyperactivity Disorder.

Objectives: In a previous pivotal study of children and adolescents (aged 6-17 years) with attention-deficit/hyperactivity disorder (ADHD), dose-optimized SHP465 mixed amphetamine salts (MAS) extended-release (12.5-25 mg once daily) was superior to placebo in reducing ADHD symptoms. This study evaluated the efficacy, tolerability, and safety of 6.25 mg SHP465 MAS once daily (one-half the lowest approved dose for adolescents and adults) versus placebo in children aged 6-12 years with ADHD. Methods: Children (aged 6-12 years) with Diagnostic and Statistical Manual of Mental Disorders, Fifth edition-defined ADHD; baseline ADHD-Rating Scale, Fifth Edition, Child, Home Version total scores (ADHD-RS-5-HV-TS) ≥28; and baseline Clinical Global Impressions-Severity scores ≥4 were eligible. Participants received 6.25 mg SHP465 MAS once daily or placebo for 4 weeks. The primary (ADHD-RS-5-HV-TS change from baseline at week 4) and key secondary (Clinical Global Impressions-Improvement [CGI-I] score at week 4) efficacy end points were assessed using linear mixed-effects models for repeated measures. Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital sign changes. Results: Of 89 randomized participants, 83 completed the study (placebo, n = 41; SHP465 MAS, n = 42). At week 4, the least squares mean (95% confidence interval) treatment differences (SHP465 MAS-placebo) were not statistically significant for ADHD-RS-5-HV-TS change (-1.9 [-6.8 to 3.1], p = 0.451; effect size [ES] = 0.17) or CGI-I score (-0.1 [-0.5 to 0.3], nominal p = 0.597; ES = 0.12). The percentage of participants reporting TEAEs was 16.3% with placebo and 24.4% with SHP465 MAS. The most frequently reported TEAEs (placebo; SHP465 MAS) were headache (7.0%; 4.4%) and decreased appetite (4.7%; 2.2%). Minimal increases in blood pressure were observed with SHP465 MAS at the final on-treatment assessment. Conclusions: SHP465 MAS 6.25 mg once daily (one-half the lowest dose approved for adolescents and adults) was well tolerated in children aged 6-12 years but was not superior to placebo in reducing ADHD symptoms, suggesting that this dose of SHP465 MAS was subtherapeutic in this age group. The Clinical Trial Registration number: NCT03325881.

Efficacy and Safety of HLD200, Delayed-Release and Extended-Release Methylphenidate, in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Evening-dosed HLD200 is a delayed-release and extended-release methylphenidate (DR/ER-MPH) formulation consisting of uniform, dual-layered microbeads with an inner drug-loaded core. DR/ER-MPH is designed to delay the initial release of drug by 8-10 hours, and thereafter, provide a controlled, extended drug release to target onset of effect upon awakening that lasts into the evening. This phase 3 study evaluated the safety and efficacy of DR/ER-MPH on symptoms and temporal at-home functional impairment in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: This 3-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group, forced-dose titration trial evaluated DR/ER-MPH (40-80 mg/day) in children aged 6-12 years with ADHD. Primary efficacy endpoint was the ADHD rating scale-IV (ADHD-RS-IV), and the key secondary endpoints were the Before-School Functioning Questionnaire (BSFQ), and Parent Rating of Evening and Morning Behavior-Revised, morning (PREMB-R AM) and evening (PREMB-R PM). Safety measures included spontaneously reported treatment-emergent adverse events (TEAEs) and two TEAEs of special interest, appetite suppression and insomnia (with direct questioning on sleep disturbance). RESULTS: One hundred sixty-one participants were included in the intent-to-treat population (DR/ER-MPH, n = 81; placebo, n = 80). After 3 weeks, DR/ER-MPH achieved significant improvements versus placebo in ADHD symptoms (least-squares [LS] mean ADHD-RS-IV: 24.1 vs. 31.2; p = 0.002), and at-home early morning (LS mean BSFQ: 18.7 vs. 28.4; p < 0.001; LS mean PREMB-R AM: 2.1 vs. 3.6; p < 0.001) and late afternoon/evening (LS mean PREMB-R PM: 9.4 vs. 12.2; p = 0.002) functional impairment. Commonly reported TEAEs (≥10%) were insomnia and decreased appetite. CONCLUSIONS: DR/ER-MPH was generally well tolerated and demonstrated significant improvements versus placebo in ADHD symptoms and at-home functional impairments in the early morning, late afternoon, and evening in children with ADHD.

Efficacy and Safety of SHP465 Mixed Amphetamine Salts in the Treatment of Attention-Deficit/Hyperactivity Disorder in Adults: Results of a Randomized, Double-Blind, Placebo-Controlled, Forced-Dose Clinical Study.

OBJECTIVE: The objective of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy and safety of SHP465 mixed amphetamine salts (MAS) in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Eligible adults [aged 18-55 years; meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ADHD criteria; baseline ADHD Rating Scale with Adult Prompts (ADHD-RS-AP) total scores ≥28] were randomized 1:1:1 to placebo or forced-dose SHP465 MAS (12.5 or 37.5 mg/day) for 4 weeks. The ADHD-RS-AP total score change from baseline to week 4 (primary endpoint) and Clinical Global Impressions-Improvement score at week 4 (key secondary endpoint) were assessed using linear mixed-effects models for repeated measures. Other efficacy endpoints were changes from baseline to week 4 on the ADHD-RS-AP hyperactivity/impulsivity and inattentiveness subscales and the percentage of participants categorized as improved on the dichotomized Clinical Global Impressions-Improvement. Safety and tolerability assessments were treatment-emergent adverse events, vital sign and weight changes, Columbia-Suicide Severity Rating Scale responses, and electrocardiogram results. RESULTS: Of 369 screened participants, 275 were randomized (placebo, n = 91; 12.5 mg/day of SHP465 MAS, n = 92; 37.5 mg/day of SHP465 MAS, n = 92) and 236 completed the study (placebo, n = 80; 12.5 mg/day of SHP465 MAS, n = 80; 37.5 mg/day of SHP465 MAS, n = 76). Least-squares mean (95% confidence interval) treatment differences at week 4 significantly favored SHP465 MAS over placebo for the ADHD-RS-AP total score change from baseline [12.5 mg/day: -8.1 (-11.7, -4.4), effect size = 0.67; 37.5 mg/day: -13.4 (-17.1, -9.7), effect size = 1.11; both p < 0.001] and Clinical Global Impressions-Improvement score [12.5 mg/day: -0.8 (-1.1, -0.4), effect size = 0.68; 37.5 mg/day: -1.2 (-1.6, -0.9), effect size = 1.11; both p < 0.001]. Treatment differences for the change from baseline at week 4 favored 12.5 and 37.5 mg/day of SHP465 MAS, respectively, over placebo on the ADHD-RS-AP hyperactivity/impulsivity (both nominal p < 0.001; effect size = 0.56 and 0.91) and inattentiveness (both nominal p < 0.001; effect size = 0.70 and 1.19) subscales. At the final on-treatment assessment, the percentage of participants categorized as improved on Clinical Global Impressions-Improvement was higher with both SHP465 MAS doses than with placebo (both nominal p < 0.001). Treatment-emergent adverse events reported (>5%) with SHP465 MAS were decreased appetite, dry mouth, insomnia, headache, anxiety, initial insomnia, irritability, and bruxism. Severe treatment-emergent adverse events and treatment-emergent adverse events leading to discontinuation, respectively, were reported by 8 and 12 participants (placebo, n = 2 and 0; 12.5 mg/day SHP465 MAS, n = 1 and 7; 37.5 mg/day SHP465 MAS, n = 5 and 5). At the final on-treatment assessment, mean ± standard deviation increases from baseline were observed with 12.5 and 37.5 mg/day of SHP465 MAS for pulse (3.3 ± 10.52 and 7.1 ± 11.48 bpm) and blood pressure (systolic 0.2 ± 7.24 and 1.7 ± 9.99 mmHg; diastolic 1.0 ± 7.46 and 2.8 ± 7.90 mmHg) and decreases were observed for weight (-0.97 ± 1.523 and -1.65 ± 2.333 kg), body mass index (-0.33 ± 0.519 and -0.56 ± 0.777 kg/m2), and Fridericia corrected QT interval (-3.0 ± 10.72 and -1.6 ± 13.70 ms). No participant in any treatment group had a positive response for on-study Columbia-Suicide Severity Rating Scale assessments. CONCLUSIONS: SHP465 MAS was superior to placebo in reducing ADHD symptoms, with a safety profile consistent with other long-acting stimulants. ClinicalTrials.gov Registry Number: NCT02604407.

ADHD Symptom Rebound and Emotional Lability With Lisdexamfetamine Dimesylate in Children Aged 6 to 12 Years.

OBJECTIVE: To describe symptom rebound in children with ADHD treated with lisdexamfetamine dimesylate (LDX) or placebo. METHOD: During a 4-week, randomized, double-blind, placebo-controlled trial of LDX, parents/caregivers completed the Conners' Parent Rating Scale-Revised: Short Form symptom rating scale throughout the day. Response, rebound, and emotional lability (EL) were assessed post hoc based on predefined criteria. RESULTS: Most participants given LDX ( n = 207) were responders throughout the day (50.7%-55.6%) versus placebo ( n = 72; 11.1%-22.2%). A total of seven (3.4%) LDX participants showed rebound in the afternoon and/or evening versus seven (9.7%) with placebo. In both groups, most incidences of rebound occurred in the evening. EL (mean) was higher in LDX rebounders and nonresponders (range = 4.2-9.0) versus LDX responders (range = 1.3-1.6) and versus placebo rebounders (range = 0.7-1.9). CONCLUSION: ADHD symptom rebound occurred in few participants (3.3%) given LDX (accompanied by clinically significant EL). Overall, more participants given LDX versus placebo responded throughout the day.

Aiming for remission in adults with attention-deficit/hyperactivity disorder: The primary care goal.

Attention-deficit/hyperactivity disorder (ADHD) is often undiagnosed and undertreated in adults, resulting in wide-ranging problems and functional deficits in patients' lives. In addition, psychiatric comorbidities unrelated to symptom severity may be present. However, effective treatment that can alleviate symptoms and bring about meaningful improvements in functionality is available. Primary care providers can play a crucial role in recognizing and diagnosing ADHD, initiating and monitoring treatment, and obtaining consultations or arranging referrals when necessary, all with the goal of achieving and maintaining remission. Fulfillment of this role requires a practical understanding of the diverse clinical manifestations of ADHD in patients stratified by age and sex, and familiarity with current treatment guidelines. Although there is no absolute consensus on the criteria by which remission is defined, treatment response may be guided by objective ratings of global symptom severity and patients' self-reports of changes in their ability to cope with routine daily tasks, academic and vocational responsibilities, and social relationships. Although there has been much research into the genetic and neurophysiologic basis of ADHD, it is more important for primary care providers to appreciate that ADHD is a chronic condition requiring lifelong follow-up and that clinical presentation and response to treatment can vary widely among patients and over time in the same patients. Such variability makes the management of ADHD challenging, but the opportunity to bring about dramatic improvement in patients' lives makes it imperative for primary care providers to be competent in this area. This review provides primary care clinicians with a practical definition of remission in adults with ADHD, to emphasize that symptom reduction does not necessarily mean intact functionality, and to suggest a multidisciplinary approach aimed at achieving the greatest possible reduction of symptoms and normalization of functionality.

A 9-week, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study to evaluate the efficacy and safety of modafinil as treatment for adults with ADHD.

OBJECTIVE: This study evaluated the efficacy and tolerability of modafinil at a range of doses, versus placebo, in alleviating symptoms of ADHD in adults. METHOD: Adult patients with ADHD were randomized in 1:1:1:1:1 fashion to double-blind treatment with modafinil 255, 340, 425, or 510 mg daily or placebo for 9 weeks. The primary efficacy outcome was the change from baseline at final visit in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score. RESULTS: A total of 338 patients were enrolled, of whom 330 received at least 1 dose of study medication (modafinil or placebo). No statistically significant difference in the AISRS total score was observed at final visit between any modafinil group and placebo; however, some observations among patients who completed the trial may warrant further investigation. CONCLUSION: Modafinil was reasonably tolerated but did not demonstrate a benefit on ADHD symptoms in adults.

The effects of lisdexamfetamine dimesylate on emotional lability in children 6 to 12 years of age with ADHD in a double-blind placebo-controlled trial.

OBJECTIVE: To evaluate the effect of lisdexamfetamine dimesylate (LDX) on emotional lability (EL) in children with ADHD. METHOD: Post hoc analyses of a placebo-controlled trial of LDX-stratified children (aged 6-12 years) with ADHD to prominent and not prominent EL at baseline (score >3 or ≤3, respectively, on Conners' Parent Rating Scale [CPRS] items of anger, loss of temper, and irritability). Efficacy was assessed by change in CPRS EL scores and ADHD Rating Scale-IV (ADHD-RS-IV) total and subscale scores. Safety measures included treatment-emergent adverse events (TEAEs). RESULTS: LDX showed improvement versus placebo (p < .0005) for EL item least squares (LS) mean change scores at endpoint and throughout the day. At baseline, 138 and 73 participants randomized to LDX treatment and having baseline and endpoint CPRS scores were categorized with CPRS-derived prominent and not prominent baseline EL, respectively; 41 and 31 participants randomized to placebo were categorized with CPRS-derived prominent and not prominent baseline EL, respectively. ADHD-RS-IV total and subscale scores decreased with LDX regardless of baseline EL severity. TEAEs included decreased appetite, insomnia, upper abdominal pain, headache, and irritability. CONCLUSION: EL and ADHD symptoms improved with LDX regardless of baseline EL symptom severity. LDX demonstrated a safety profile consistent with long-acting psychostimulant use.

Effect of lisdexamfetamine dimesylate on parent-rated measures in children aged 6 to 12 years with attention-deficit/hyperactivity disorder: a secondary analysis.

UNLABELLED: To evaluate the efficacy of lisdexamfetamine dimesylate (LDX) in school-aged children with attention-deficit/hyperactivity disorder (ADHD), using the Conners' Parent Rating Scale, Revised Short Version (CPRS-R:S) and its subscales. METHODS: This was a secondary post hoc analysis of data from a placebo-controlled, double-blind, parallel-group, forced dose-escalation trial. Boys and girls aged 6 to 12 years with a primary diagnosis of ADHD were randomly assigned to LDX (30, 50, or 70 mg/d) or placebo. Improvement on the CPRS-R:S and its subscales (ADHD Index, hyperactivity, oppositional, and cognition) at 10:00 AM, 2:00 PM, and 6:00 PM was analyzed. Safety assessments included the identification of adverse events and were conducted throughout the study. RESULTS: Of the 290 patients randomized, 285 were included in the intent-to-treat population. Parents noted significant improvements at all 3 assessment times on the CPRS-R:S total score and for the CPRS-R:S ADHD Index, hyperactivity, and cognition subscales, regardless of the subject baseline disease severity. For the CPRS-R:S oppositional subscale, significant improvement was noted at 10:00 AM and 2:00 PM (P < 0.01), and overall, significant improvement occurred in subjects who were more severely ill at baseline. The tolerability of LDX was comparable to that of other stimulants. CONCLUSION: Once-daily treatment with LDX was associated with significant improvement in parent-rated assessments of ADHD-related behavior throughout the day at approximately 10:00 AM, 2:00 PM, and 6:00 PM. Lisdexamfetamine dimesylate was effective and well tolerated in this study population of children aged 6 to 12 years with ADHD.

Practice parameter for the assessment and treatment of children and adolescents with substance use disorders.

This practice parameter describes the assessment and treatment of children and adolescents with substance use disorders and is based on scientific evidence and clinical consensus regarding diagnosis and effective treatment as well as on the current state of clinical practice. This parameter considers risk factors for substance use and related problems, normative use of substances by adolescents, the comorbidity of substance use disorders with other psychiatric disorders, and treatment settings and modalities.

Practice parameter for use of electroconvulsive therapy with adolescents.

Electroconvulsive therapy (ECT) may be an effective treatment for adolescents with severe mood disorders and other Axis I psychiatric disorders when more conservative treatments have been unsuccessful. ECT may be considered when there is a lack of response to two or more trials of pharmacotherapy or when the severity of symptoms precludes waiting for a response to pharmacological treatment. The literature on ECT in adolescents, including studies and case reports, was reviewed and then integrated into clinically relevant guidelines for practitioners. Mood disorders have a high rate of response to ECT (75%-100%), whereas psychotic disorders have a lower response rate (50%-60%). Consent of the adolescent's legal guardian is mandatory, and the patient's consent or assent should be obtained. State legal guidelines and institutional guidelines must be followed. ECT techniques associated with the fewest adverse effects and greatest efficacy should be used. The presence of comorbid psychiatric disorder is not a contraindication. Systematic pretreatment and posttreatment evaluation, including symptom and cognitive assessment, is recommended.

Practice parameter for the assessment and treatment of children and adolescents with enuresis.

Enuresis is a symptom that is frequently encountered in child psychiatric evaluations. Careful assessment is required to identify specific urologic, developmental, psychosocial, and sleep-related etiologies. For most children with enuresis, however, a specific etiology cannot be determined. Treatment then involves supportive approaches, conditioning with a urine alarm, or medications--imipramine or desmopressin acetate. The psychosocial consequences of the symptom must be recognized and addressed with sensitivity during the evaluation and treatment of enuresis.

Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults.

This practice parameter describes treatment with stimulant medication. It uses an evidence-based medicine approach derived from a detailed literature review and expert consultation. Stimulant medications in clinical use include methylphenidate, dextroamphetamine, mixed-salts amphetamine, and pemoline. It carries FDA indications for treatment of attention-deficit/hyperactivity disorder and narcolepsy.

Practice parameter for the prevention and management of aggressive behavior in child and adolescent psychiatric institutions, with special reference to seclusion and restraint.

This parameter reviews the current state of the prevention and management of child and adolescent aggressive behavior in psychiatric institutions, with particular reference to the indications and use of seclusion and restraint. It also presents guidelines that have been developed in response to professional, regulatory, and public concern about the use of restrictive interventions with aggressive patients with regard to personal safety and patient rights. The literature on the use of seclusion, physical restraint, mechanical restraint, and chemical restraint is reviewed, and procedures for carrying out each of these interventions are described. Clinical and regulatory agency perspectives on these interventions are presented. Effectiveness, indications, contraindications, complications, and adverse effects of seclusion and restraint procedures are addressed. Interventions are presented to provide more opportunities to promote patient independence and satisfaction with treatment while diminishing the necessity of using restrictive procedures.