Management of Facial Nerve Schwannoma: A Multicenter Study of 50 Cases.

Objective In the management of facial nerve schwannoma (FNS), surgical tumor resection is now often being replaced with more conservative approaches, such as observation with serial imaging or stereotactic radiosurgery (SRS). Given the scarcity of these lesions, determining the optimal management of FNS remains challenging and subject of debate with multiple treatment approaches supported in the literature. Methods A retrospective chart review was performed in two academic centers for patients diagnosed with FNS between 1996 and 2017. The clinical presentation, treatment modalities employed, tumor control rates, and facial nerve function (FNF) outcomes (House-Brackmann system) were assessed and analyzed. Results The study comprised 50 adult patients. Initial treatment modalities included observation with serial clinicoradiologic review in 27 patients (54%), surgery in 17 patients (34%), and SRS in 6 patients (12%). The FNF were decreased in more than half of the patients who had surgery. Nonetheless, more than 80% of the patients who were initially managed with observation or SRS had stable or improved FNF. Conclusion A prevailing trend toward more conservative treatment modalities for FNS has evolved over time, providing relatively long-term preservation of FNF. As there are multiple management options available, it is of paramount importance that the treating physician be familiar with all treatment modalities and outcomes and counsel patients appropriately. The surgery should be reserved for large tumors and poor FNF at initial presentation or follow-up while watchful observation with imaging is the treatment of choice for rest of the patients.

The pattern of hearing outcome following surgery of the semicircular canals.

OBJECTIVE: To analyze demographic, clinical, surgical, and audiometric factors that may affect hearing outcome following surgery for the semicircular canals (SCC). METHOD: This is a retrospective case review of adults who underwent surgeries for superior SCC (SSCC), lateral SCC (LSCC), or posterior SCC (PSCC) and whose data were extracted and analyzed for factors affecting the hearing outcome in these procedures. RESULTS: Thirteen patients underwent surgery for SSCC, seven cases for the LSCC, one for the PSCC, and one case of combined PSCC/SSCC surgery. The mean age was 49.8 ± 12 years (21-66). There was no difference between the preoperative and postoperative pure tone average (PTA) thresholds at 0.5-3 kHz. Higher thresholds were noted at 4, 6, and 8 kHz postoperatively. Deterioration (>10 dB) in the bone-conduction (BC) PTA was demonstrated in 3 of 22 (13.6%) cases with no significant difference in the demographic, clinical, surgical, and preoperative audiometric parameters relative to the cases without PTA BC change. A significantly larger difference in PTA BC (pre- vs. postoperative) was seen for males. Small effect size was noted for Air conduction (AC) PTA in males, and moderate effect size for Word Recognition Score (WRS) in surgery for the LSCC compare to SSCC. CONCLUSIONS: SCC surgeries carry a relatively low risk of deterioration in PTA BC. High frequency thresholds should also be included in postoperative hearing outcome assessment. Cases of LSCC for intractable Meniere's disease and surgery in males carry higher risk of poor postoperative hearing outcomes. Level of Evidence: 4.

Otosclerosis: From Genetics to Molecular Biology.

Over the past several years, with the evolution of genetic and molecular research, several etiologic factors have been implicated in the pathogenesis of otosclerosis. Overall, current evidence suggests that otosclerosis is a complex disease with a variety of potential pathways contributing to the development of abnormal bone remodeling in the otic capsule. These pathways involved in the pathogenesis of otosclerosis are influenced by both genetic and environmental factors.

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.

Characteristics and use of treatment modalities of patients with binge-eating disorder in the Department of Veterans Affairs.

OBJECTIVE: In 2013 binge-eating disorder (BED) was recognized as a formal diagnosis, but was historically included under the diagnosis code for eating disorder not otherwise specified (EDNOS). This study compared the characteristics and use of treatment modalities in BED patients to those with EDNOS without BED (EDNOS-only) and to matched-patients with no eating disorders (NED). METHODS: Patients were identified for this study from electronic health records in the Department of Veterans Affairs from 2000 to 2011. Patients with BED were identified using natural language processing and patients with EDNOS-only were identified by ICD-9 code (307.50). First diagnosis defined index date for these groups. NED patients were frequency matched to BED patients up to 4:1, as available, on age, sex, BMI, depression, and index month encounter. Baseline characteristics and use of treatment modalities during the post-index year were compared using t-tests or chi-square tests. RESULTS: There were 593 BED, 1354 EDNOS-only, and 1895 matched-NED patients identified. Only 68 patients with BED had an EDNOS diagnosis. BED patients were younger (48.7 vs. 49.8years, p=0.04), more were male (72.2% vs. 62.8%, p<0.001) and obese (BMI 40.2 vs. 37.0, p<0.001) than EDNOS-only patients. In the follow-up period fewer BED (68.0%) than EDNOS-only patients (87.6%, p<0.001), but more BED than NED patients (51.9%, p<0.001) used at least one treatment modality. DISCUSSION: The characteristics of BED patients were different from those with EDNOS-only and NED as was their use of treatment modalities. These differences highlight the need for a separate identifier of BED.

Healthcare costs and resource utilization of patients with binge-eating disorder and eating disorder not otherwise specified in the Department of Veterans Affairs.

OBJECTIVE: The objective of this study was to compare the one-year healthcare costs and utilization of patients with binge-eating disorder (BED) to patients with eating disorder not otherwise specified without BED (EDNOS-only) and to matched patients without an eating disorder (NED). METHODS: A natural language processing (NLP) algorithm identified adults with BED from clinical notes in the Department of Veterans Affairs (VA) electronic health record database from 2000 to 2011. Patients with EDNOS-only were identified using ICD-9 code (307.50) and those with NLP-identified BED were excluded. First diagnosis date defined the index date for both groups. Patients with NED were randomly matched 4:1, as available, to patients with BED on age, sex, BMI, depression diagnosis, and index month. Patients with cost data (2005-2011) were included. Total healthcare, inpatient, outpatient, and pharmacy costs were examined. Generalized linear models were used to compare total one-year healthcare costs while adjusting for baseline patient characteristics. RESULTS: There were 257 BED, 743 EDNOS-only, and 823 matched NED patients identified. The mean (SD) total unadjusted one-year costs, in 2011 US dollars, were $33,716 ($38,928) for BED, $37,052 ($40,719) for EDNOS-only, and $19,548 ($35,780) for NED patients. When adjusting for patient characteristics, BED patients had one-year total healthcare costs $5,589 higher than EDNOS-only (p = 0.06) and $18,152 higher than matched NED patients (p < 0.001). DISCUSSION: This study is the first to use NLP to identify BED patients and quantify their healthcare costs and utilization. Patients with BED had similar one-year total healthcare costs to EDNOS-only patients, but significantly higher costs than patients with NED.

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.

ADHD in the College Setting: Current Perceptions and Future Vision.

OBJECTIVE: To assess perceptions concerning ADHD among U.S. college healthcare providers. METHOD: A 37-question survey was conducted from October 4 to December 2, 2010. Participants were contacted via mail or telephone and compensated for participation. RESULTS: Thirty-eight percent of the respondents (physicians, n = 59; nurses, n = 138; directors, n = 101) viewed ADHD as a "problem"/"very much a problem" at their institution. Referrals for evaluation came from students (84%), psychologists/counselors (68%), or the institution (68%). Although 48% of respondents felt "comfortable"/"very comfortable" in their ability to recognize ADHD, 92% referred students for evaluation. Most respondents (>90%) agreed medication use may be warranted; 52% of respondents who treat ADHD or consult with a specialist (from 95% of physicians to 31% of directors) prescribed pharmacotherapy. CONCLUSION: Although college healthcare providers recognize the importance of treating ADHD, their discomfort in diagnosing and treating ADHD represents a barrier to care for college students.

Relationship of ADHD symptoms and global illness severity in adults treated with lisdexamfetamine dimesylate.

UNLABELLED: The relationship between attention-deficit/hyperactivity disorder (ADHD) symptoms and global clinical assessment of functionality is complex. This post-hoc analysis explores this relationship and suggests implications for patient assessment in clinical practice. Adults with ADHD on a stable lisdexamfetamine dimesylate (LDX) dose for ≥ 6 months were enrolled in a double-blind, placebo-controlled, randomized withdrawal study. Participants entered a 3-week open-label phase continuing their prior LDX dose and were then randomized to placebo or the same LDX dose for a 6-week, double-blind, randomized withdrawal phase. ADHD symptom distribution was measured by the ADHD Rating Scale IV (ADHD-RS-IV) with Adult Prompts total score reflecting DSM-IV-TR ADHD symptom criteria and severity by Clinical Global Impressions-Severity (CGI-S) ratings at study entry and at end of study. Of 123 participants enrolled in the open-label phase, 116 were included in the randomized withdrawal phase (placebo, n = 60; LDX, n = 56). As reported in a prior publication, mean (standard deviation) ADHD-RS-IV total score change from baseline (week 3) to end of study (randomized-withdrawal phase) was 16.8 (11.80) for placebo and 1.6 (8.63) for LDX. At end of study, for placebo and LDX, 5.0% and 32.1% of participants, respectively, had a CGI-S = 1, 11.7% and 35.7% had a CGI-S = 2, 11.7% and 17.9% had a CGI-S = 3, 33.3% and 7.1% had a CGI-S = 4, 35.0% and 7.1% had a CGI-S = 5, and 3.3% and 0% had a CGI-S = 6; no participants had a CGI-S = 7 (P < 0.0001). The CGI-S ratings increased (worsened) as ADHD symptom scores worsened. Post-hoc regression analysis between ADHD-RS-IV scores and CGI-S demonstrated shared variance of 47% at week 3 and 69% for both placebo and LDX at end of study. Although ADHD symptom scores demonstrate a linear relationship with global illness severity, the variance suggests that other factors not captured by symptom scales are also important in assessing patient outcomes in clinical practice. ( TRIAL REGISTRATION: ClinicalTrials.gov NCT00877487.).

The patient experience with DSM-5-defined binge eating disorder: characteristics, barriers to treatment, and implications for primary care physicians.

BACKGROUND: Binge eating disorder (BED) is now a formal diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). However, post-DSM-5 patient profiles and viewpoints on BED diagnosis and treatment remain unclear. This study used a focus group methodology to examine demographic and clinical characteristics, as well as perceptions of diagnosis and treatment from patients with BED symptoms who were either formally diagnosed with BED or undiagnosed. METHODS: Binge eating disorder-diagnosed individuals (n = 11) or those meeting the DSM-5 BED diagnostic criteria but were undiagnosed (n = 14) participated in 6 semistructured focus groups conducted by trained staff at 3 geographic locations in the United States. Patients completed a series of demographic and clinical measures and then engaged in a moderated discussion focused on identifying factors associated with their experiences with BED. RESULTS: Sixty percent of the patients were female, 48% were white and 40% were black, and 76% were employed. The diagnosed group had a slightly higher socioeconomic status; undiagnosed patients had a higher average body mass index. In the overall sample, comorbid anxiety (40%) and depression (40%) were the most common psychiatric comorbidities. Even in the diagnosed group, only half of the patients (54.5%) became aware of BED through their health care provider (HCP; n = 6). Patients perceived that HCPs were focused more on physical ailments, were judgmental about weight, and were unable to distinguish BED from obesity. They also expressed a desire for safe, nonjudgmental interactions with HCPs. CONCLUSIONS: Education and income may be factors affecting access to care and BED diagnosis. Both patient groups reported considerable psychopathology and medical comorbidities. Moreover, the patient groups perceived HCPs as both having inadequate understanding of BED and providing insensitive and ineffective communication regarding eating behaviors. The study findings in diagnosed and undiagnosed patient groups underscore the need for greater BED disease state awareness and patient sensitivity among HCPs.

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.

The diagnosis less traveled: NPs' role in recognizing adult ADHD.

PURPOSE: To stimulate critical thought about sociocultural implications of unrecognized and undiagnosed attention deficit hyperactivity disorder (ADHD), and how these factors interface with healthcare delivery models and care that nurse practitioners (NPs) provide. DATA SOURCES: Health science databases--Psych Info, Proquest, Sage, PubMed, and authors' professional experiences. CONCLUSIONS: NPs, often the main healthcare provider for underserved populations in community practice settings, have little training in assessing adult ADHD. ADHD, often unrecognized and undiagnosed among adults, contributes to global impairments adversely affecting individuals' social, behavioral, academic, and cognitive functioning. Increased insight and awareness about adult ADHD is warranted to facilitate appropriate diagnosis. IMPLICATIONS FOR PRACTICE: ADHD is found in all sectors of our society; however, assessment and diagnosis among those whose socioeconomic status limits access to resources is a problem. Working in integrated care clinical settings facilitates recognition of patient problems and colocates resources required to manage the ADHD patient effectively. While this practice model may not be the norm, it is critical for NPs to have: (a) heightened awareness of the presentation of adult ADHD; (b) skills and/or resources to facilitate proper diagnosis of adult ADHD, and (c) models of practice that support optimal NP care delivery.

Treatment outcomes with lisdexamfetamine dimesylate in children who have attention-deficit/hyperactivity disorder with emotional control impairments.

OBJECTIVE: The purpose of this study was to assess lisdexamfetamine dimesylate (LDX) treatment effects based on baseline emotional control dysfunction in children with attention-deficit/hyperactivity disorder (ADHD) categorized with or without impairments of executive function (EF) emotional control. METHODS: Post-hoc analyses of a 7 week, open-label LDX study in children with ADHD (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision [DSM-IV-TR] defined) and impairments in EF control of emotional response. At baseline, participants were dichotomized by Behavior Rating Inventory of EF (BRIEF) emotional control domain T-scores of ≥65 (with impairment) or <65 (without impairment). ADHD Rating Scale-IV (ADHD-RS-IV), BRIEF Global Executive Composite and emotional control domain, Expression and Emotion Scale for Children (EESC) scores, Pearson correlations for BRIEF versus ADHD-RS-IV and EESC, and Clinical Global Impressions scores were assessed at baseline and end of study (week 7)/early termination (EOS/ET) by baseline category of BRIEF emotional control impairment. Safety assessments included treatment-emergent adverse events (TEAEs). RESULTS: At baseline and EOS/ET, respectively, 53.0% and 20.7% met criteria for emotional control impairment. Participants with and without emotional control impairments had similar ADHD-RS-IV change scores. Mean (SD) change from baseline for those with and without emotional control impairments were -20.8 (12.89) and -14.6 (11.25) for BRIEF global scores and -16.0 (13.19) and -5.0 (9.48) for BRIEF emotional control domain scores. Participants with emotional control impairments had greater mean EESC total score changes. BRIEF emotional control domain and all ADHD-RS-IV scores indicated moderate correlations between change scores (all p<0.0001). Overall, 84.9% of participants had TEAEs (mostly mild-to-moderate in severity); 3.8% discontinued because of TEAEs. CONCLUSIONS: The proportion of children with behavioral impairments in EF control of emotional response decreased during LDX treatment. ADHD symptoms improved in both groups. The moderate correlations between EF behaviors and ADHD symptoms suggest there may be utility in evaluating behavioral domains beyond core ADHD symptoms.

Efficacy and safety of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder and recent methylphenidate use.

INTRODUCTION: Lisdexamfetamine dimesylate (LDX) is a long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). Post hoc subgroup analyses were performed from two studies in children with ADHD to compare the efficacy of LDX in participants who had received prior methylphenidate (MPH) treatment with that of the overall study populations. METHODS: Study 1 (7-week; open-label design) and study 2 (randomized, double-blind, placebo-controlled, crossover, laboratory school design) enrolled children aged 6-12 years with ADHD and baseline ADHD Rating Scale IV (ADHD-RS-IV) total score ≥28. Both studies excluded children whose prestudy ADHD treatment provided effective control of ADHD symptoms with an acceptable safety profile. Post hoc efficacy analyses were performed in children who had received MPH within 6 months of study enrollment. Efficacy measures included the following scales: ADHD-RS-IV, Clinical Global Impressions-Improvement (CGI-I), Expression and Emotion Scale for Children (EESC), Behavior Rating Inventory of Executive Function (BRIEF), Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP), and Permanent Product Measure of Performance (PERMP). RESULTS: In studies 1 and 2, 83/318 (26%) and 67/129 (52%) participants, respectively, had received MPH within 6 months and were not adequately controlled on current medication with acceptable tolerability; most of these participants had received long-acting MPH. In prior MPH participants, efficacy assessments demonstrated improvements from baseline (study 1) and versus placebo (study 2) that were comparable with those seen in the respective overall study population. Safety profiles were consistent with long-acting stimulant use. CONCLUSION: In two studies, children who had received prior MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study populations. For children with ADHD who were previously treated with MPH, LDX may, therefore, be an efficacious treatment option.

Parent-reported executive function behaviors and clinician ratings of attention-deficit/hyperactivity disorder symptoms in children treated with lisdexamfetamine dimesylate.

OBJECTIVE: The purpose of this article was to describe the relationships between parent-rated executive function (EF) and clinician-rated attention-deficit/hyperactivity disorder (ADHD) symptoms before and after lisdexamfetamine dimesylate (LDX) treatment in children with and without EF deficit. METHODS: In post-hoc analyses of children with ADHD who participated in a 7 week open-label, dose-optimized (LDX 20-70 mg/day) trial, ADHD Rating Scale-IV (ADHD-RS-IV) change scores were compared (using two-sample t tests) between youth with and without clinically significant EF impairment at baseline. Clinically significant impairment was defined as parent-rated Behavior Rating Inventory of EF (BRIEF) Global Executive Composite (GEC) t scores ≥65. Relationships between baseline and endpoint BRIEF and ADHD-RS-IV scores were examined using Pearson correlations and generalized effect linear model. Safety assessment included treatment-emergent adverse events (TEAEs). RESULTS: At baseline, 265/315 participants (84.1%) had a clinically significant BRIEF score. Their mean (SD) ADHD-RS-IV total score at baseline was 42.1 (6.64) for those with, and 36.5 (6.67) for those without, clinically significant BRIEF. At endpoint, ADHD-RS-IV total and subscale scores were significantly improved (p<0.0001) for both those with and those without clinically significant baseline BRIEF scores. Moderately strong, positive Pearson correlations were observed between BRIEF and ADHD-RS-IV total and subscale scores. In the generalized effect linear model, ADHD-RS-IV change scores were significantly correlated with endpoint BRIEF scores (r(2)=0.35, ß=0.73, p<0.0001). In the subgroup without clinically significant BRIEF t scores at endpoint, parents and clinicians rated 90% and 95%, respectively, as improved. In the subgroup with clinically significant BRIEF t scores at endpoint, parents and clinicians rated 69% and 78%, respectively, as improved. TEAEs were experienced by 269/318 (84.9%) participants; most (82.7%) experienced events mild to moderate in intensity. A total of 12/318 (4.1%) participants discontinued because of TEAEs. CONCLUSION: Clinically significant impairment of EF behaviors in children with ADHD was associated with more severe ADHD symptoms. LDX therapy improved ADHD symptom severity, and at endpoint, fewer participants displayed impairment of EF behaviors (versus baseline). The parent-rated BRIEF may describe clinically important EF behaviors not assessed by the 18-item ADHD-RS-IV.

Clinical response and symptomatic remission in short- and long-term trials of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: Despite the overall high degree of response to pharmacotherapy, consensus is lacking on how to judge clinical response or define optimal treatment/remission when treating adults with attention-deficit/hyperactivity disorder (ADHD). This study examined clinical response and symptomatic remission in analyses of 2 studies of lisdexamfetamine dimesylate (LDX) in adults with ADHD. METHODS: In a 4-week, double-blind, forced-dose trial, adults with ADHD were randomized to LDX 30, 50, and 70 mg/day (mg/d) or placebo. In a second, open-label, follow-up trial, adults entering from the 4-week study were titrated to an "optimal" LDX dose (30 mg/d [n=44], 50 mg/d [n=112], and 70 mg/d [n=171]) over 4 weeks, and maintained for 11 additional months. The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts and the Clinical Global Impressions-Improvement (CGI-I) scale assessed efficacy. Clinical response was defined, post hoc, as ≥30% reduction from baseline in ADHD-RS-IV and CGI-I rating of 1 or 2; symptomatic remission was defined as ADHD-RS-IV total score ≤18. Log rank analysis examined overall significance among the treatment groups in time to response or remission. RESULTS: Four hundred and fourteen participants in the 4-week study and 345 in the open-label, extension study were included in the efficacy populations. All LDX groups improved by ADHD-RS-IV and CGI-I scores in both studies. In the 4-week study (n=414), 69.3% responded and 45.5% achieved remission with LDX (all doses); 37.1% responded and 16.1% achieved remission with placebo; time (95% CI) to median clinical response (all LDX doses) was 15.0 (15.0, 17.0) days and to remission was 31.0 (28.0, 37.0) days (P<.0001 overall). In the open-label study, with LDX (all doses), 313 (95.7%) and 278 (85.0%) of 327 participants with evaluable maintenance-phase data met criteria for response and remission, respectively. Of participants who completed dose optimization, 75.2% remained responders and 65.7% remained in remission in the 12-month study. Overall, 285 (82.6%) and 227 (65.8%) of 345 participants were responders and remitters, respectively, at their final visits. CONCLUSION: In the long-term study, with open-label, dose-optimized LDX treatment, most adults with ADHD achieved clinical response and/or symptomatic remission; almost two-thirds maintained symptomatic remission over the remaining 11 months. TRIAL REGISTRATION: Clinical Trial Numbers: NCT00334880 and NCT01070394CLINICAL TRIAL REGISTRY: clinicaltrials.gov.

Efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder previously treated with amphetamines: analyses from a randomized, double-blind, multicenter, placebo-controlled titration study.

BACKGROUND: To examine the efficacy of lisdexamfetamine dimesylate (LDX) in adults with attention-deficit/hyperactivity disorder (ADHD) who remained symptomatic (ADHD Rating Scale IV [ADHD-RS-IV] total score >18) on amphetamine (AMPH) therapy (mixed AMPH salts and/or d-AMPH formulations) prior to enrollment in a 4-week placebo-controlled LDX trial vs the overall study population. In these post hoc analyses from a multicenter, randomized, double-blind, forced-dose titration study, clinical efficacy of LDX (30-70 mg/d) in adults with ADHD receiving AMPH treatment at screening vs the overall study population was evaluated. ADHD symptoms were assessed using the ADHD-RS-IV with adult prompts at screening, baseline (after prior treatment washout), and endpoint. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, laboratory findings, and electrocardiogram. RESULTS: Of 414 participants (62, placebo; 352, LDX) included in the overall study population, 41 were receiving AMPH therapy at screening (2, placebo; 39, LDX); mean AMPH dose was 35.0 and 34.1 mg/d for participants in placebo and all LDX groups, respectively. Of the 41 participants, 36 remained symptomatic (ADHD-RS-IV >18) at screening despite receiving AMPH. For the 36 participants in the placebo (n = 2) and LDX (n = 34) groups, respectively, at endpoint, mean change from screening ADHD-RS-IV total scores were -5.5 and -14.8 and from baseline scores were -13.5 and -17.8. For the overall study population, endpoint mean change from baseline ADHD-RS-IV total scores were -7.8 for placebo and -17.5 for LDX. In the prior AMPH subgroup, 2/2 (100.0%) in the placebo group and 22/39 (56.4%) participants in the LDX (all doses) group reported any TEAE. Events that occurred in ≥5% for LDX were dry mouth (5/39; 12.8%), headache (5/39; 12.8%), fatigue (3/39; 7.7%), insomnia (3/39; 7.7%), decreased appetite (2/39; 5.1%), and nausea (2/39; 5.1%). None of these events occurred in the 2 placebo patients with prior AMPH use. CONCLUSION: In these post hoc analyses, adults with significant baseline ADHD symptoms despite adequate AMPH treatment dose showed similar improvements in ADHD symptoms with LDX treatment as the overall study population. Prospective studies are needed to confirm these findings. The safety profile of LDX in the overall study population was consistent with long-acting psychostimulant use. TRIAL REGISTRY: Study to Assess the Safety and Efficacy of NRP104 in Adults With Attention-Deficit Hyperactivity Disorder (ADHD). Clinicaltrials.gov Identifier: NCT00334880.

Attention deficit hyperactivity disorder subtypes and symptom response in adults treated with lisdexamfetamine dimesylate.

OBJECTIVE: To evaluate the efficacy of lisdexamfetamine dimesylate in adults with attention deficit hyperactivity disorder symptom subtypes who exhibit predominantly inattention, hyperactivity/ impulsivity, or combined symptom clusters. DESIGN/SETTING/PARTICIPANTS: This is a post-hoc analysis from a multicenter, one-year, open-label lisdexamfetamine dimesylate study in adults with attention deficit hyperactivity disorder previously completing two weeks or more in a four-week, randomized, placebo-controlled lisdexamfetamine dimesylate study, using Attention Deficit Hyperactivity Disorder Rating Scale IV symptom ratings as an attention deficit hyperactivity disorder subtype proxy (N=349). MEASUREMENTS: Attention Deficit Hyperactivity Disorder Rating Scale IV was measured at baseline of prior study and throughout the open-label study. Proxy subtypes were based on item scores of 2 (moderate) or 3 (severe), representing endorsement of at least six of nine symptoms on respective subscales; predominantly combined type endorsed at least six of nine symptoms on each subscale. Overall safety evaluations included treatment-emergent adverse events. RESULTS: At baseline, 93 of 345 participants exhibited predominantly inattention, 13 predominantly hyperactivity/ impulsivity, 236 combined symptom clusters, and three were unassigned. For the three subgroups, respectively, mean (standard deviation) Attention Deficit Hyperactivity Disorder Rating Scale IV total scores at baseline were 34.5 (4.02), 33.8 (3.27), and 43.6 (5.24); change from baseline to endpoint scores were -19.3 (9.48), -24.0 (7.22), and -27.3 (11.78). Mean (standard deviation) end-of-study lisdexamfetamine dimesylate dose was 57.7 (14.75), 53.1 (16.01), and 56.9 (14.94)mg/day, respectively.Treatment-emergent adverse events (>5%) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), irritability (11.2%), anxiety (8.3%), nasopharyngitis (7.4%), sinusitis (6.6%), decreased weight (6.0%), back pain (5.4%), and muscle spasms (5.2%). CONCLUSIONS: Lisdexamfetamine dimesylate was effective in participants with predominantly inattention, hyperactivity/ impulsivity, and combined attention deficit hyperactivity disorder symptom clusters. Groups exhibiting specific predominant subtype symptoms did not differ in clinical response to lisdexamfetamine dimesylate.

Lifespan persistence of ADHD: the life transition model and its application.

BACKGROUND: The understanding that attention-deficit/hyperactivity disorder (ADHD) often persists throughout life has heightened interest of patients, families, advocates, and professionals in a longitudinal approach to management. Such an approach must recognize and address known patient- and systems-based challenges of long-term mental health treatment, shifting of clinical presentations of ADHD, and commonality of psychiatric comorbidity with ADHD. OBJECTIVE: The ADHD Life Transition Model is a step toward developing criteria to optimize recognition and clinical management of ADHD (eg, response, remission) across an individual's lifespan and across diverse medical subspecialties. To support therapeutic efficiency and adaptability, our proposed model highlights periods when external resources for managing ADHD are reduced, cognitive and behavioral stressors are increased, and individuals may be reevaluating how they perceive, accept, and adhere to ADHD treatment. Such a model aims to support the clinical community by placing in context new findings, which suggest that the prevention of adult psychopathology in individuals with pediatric ADHD may be possible. CONCLUSIONS: The ADHD Life Transition Model seeks to improve care for individuals with ADHD by (1) underscoring that ADHD persists beyond childhood in at least two-thirds of patients, (2) raising awareness of the need to approach ADHD from a chronic illness standpoint, and (3) increasing mental health professionals' diligence in symptom recognition and management of ADHD across developmental phases from childhood through adulthood.