Premorbid body weight predicts weight loss in both anorexia nervosa and atypical anorexia nervosa: Further support for a single underlying disorder.

OBJECTIVE: For adolescents, DSM-5 differentiates anorexia nervosa (AN) and atypical AN with the 5th BMI-centile-for-age. We hypothesized that the diagnostic weight cut-off yields (i) lower weight loss in atypical AN and (ii) discrepant premorbid BMI distributions between the two disorders. Prior studies demonstrate that premorbid BMI predicts admission BMI and weight loss in patients with AN. We explore these relationships in atypical AN. METHOD: Based on admission BMI-centile < or ≥5th, participants included 411 female adolescent inpatients with AN and 49 with atypical AN from our registry study. Regression analysis and t-tests statistically addressed our hypotheses and exploratory correlation analyses compared interrelationships between weight loss, admission BMI, and premorbid BMI in both disorders. RESULTS: Weight loss in atypical AN was 5.6 kg lower than in AN upon adjustment for admission age, admission height, premorbid weight and duration of illness. Premorbid BMI-standard deviation scores differed by almost one between both disorders. Premorbid BMI and weight loss were strongly correlated in both AN and atypical AN. DISCUSSION: Whereas the weight cut-off induces discrepancies in premorbid weight and adjusted weight loss, AN and atypical AN overall share strong weight-specific interrelationships that merit etiological consideration. Epidemiological and genetic associations between AN and low body weight may reflect a skewed premorbid BMI distribution. In combination with prior findings for similar psychological and medical characteristics in AN and atypical AN, our findings support a homogenous illness conceptualization. We propose that diagnostic subcategorization based on premorbid BMI, rather than admission BMI, may improve clinical validity. PUBLIC SIGNIFICANCE: Because body weights of patients with AN must drop below the 5th BMI-centile per DSM-5, they will inherently require greater weight loss than their counterparts with atypical AN of the same sex, age, height and premorbid weight. Indeed, patients with atypical AN had a 5.6 kg lower weight loss after controlling for these variables. In comparison to the reference population, we found a lower and higher mean premorbid weight in patients with AN and atypical AN, respectively. Considering previous psychological and medical comparisons showing little differences between AN and atypical AN, we view a single disorder as the most parsimonious explanation. Etiological models need to particularly account for the strong relationship between weight loss and premorbid body weight.

Exploring the Relationship between Adherence to Therapy, Treatment Acceptability, and Clinical Outcomes in Adults with Attention-Deficit/Hyperactivity Disorder: Results from the COMPAS Multicenter Randomized Controlled Trial.

INTRODUCTION: Cognitive behavioral therapy and dialectical behavior therapy (DBT) can be effective in treating adults with ADHD, and patients generally consider these interventions useful. While adherence, as measured by attendance at sessions, is mostly sufficient, adherence to therapy skills has not been assessed. Furthermore, the relationship between patient evaluation of therapy effectiveness, treatment adherence, and clinical outcomes is understudied. OBJECTIVE: This study aimed to examine treatment acceptability and adherence in relation to treatment outcomes in a large randomized controlled trial comparing a DBT-based intervention with a nonspecific active comparison, combined with methylphenidate or placebo. METHOD: A total of 433 adult patients with ADHD were randomized. Participants reported how effective they found the therapy, and adherence was measured by attendance at therapy sessions and by self-reports. Descriptive, between-groups, and linear mixed model analyses were conducted. RESULTS: Participants rated psychotherapy as moderately effective, attended 78.40-94.37% of sessions, and used skills regularly. The best-accepted skills were sports and mindfulness. Groups receiving placebo and/or nonspecific clinical management rated their health condition and the medication effectiveness significantly worse than the psychotherapy and methylphenidate groups. Improvements in clinical outcomes were significantly associated with treatment acceptability. Subjective (self-reported) adherence to psychotherapy was significantly associated with improvements in ADHD symptoms, clinical global efficacy and response to treatment. DISCUSSION: These results further support the acceptability of DBT for adult ADHD and suggest the need to address adherence to treatment to maximize clinical improvements. Results may be limited by the retrospective assessment of treatment acceptability and adherence using an ad hoc instrument.

Exploring the efficacy of dialectical behaviour therapy and methylphenidate on emotional comorbid symptoms in adults with attention Deficit/Hyperactivity disorder: Results of the COMPAS multicentre randomised controlled trial.

This study evaluated the efficacy of dialectical behaviour group therapy (GPT) vs. individual clinical management (CM) and methylphenidate (MPH) vs. placebo (PLB) on emotional symptoms in adults with ADHD. This longitudinal multicentre RCT compared four groups (GPT+MPH, GPT+PLB, CM+MPH, and CM+PLB) over five assessment periods, from baseline to week 130. Emotional symptomatology was assessed using SCL-90-R subscales. Of the 433 randomised participants, 371 remained for final analysis. At week 13, the GPT+MPH group showed smaller reductions in anxiety symptoms than the CM groups, but the differences disappeared at subsequent assessments. Improvements in emotional symptom were significantly predicted by reductions in core ADHD symptoms in all groups except the GPT+MPH group. The unexpected lack of between-group differences may be explained by a "floor effect", different intervention settings (group vs. individual), and psychotherapy type. Multiple regression analyses suggest a more specific effect of combined interventions (GPT+MPH). Implications for clinical practice are discussed. Clinical trial registration: ISRCTN54096201 (Current Controlled Trials).

The importance of familial risk factors in children with ADHD: direct and indirect effects of family adversity, parental psychopathology and parenting practices on externalizing symptoms.

BACKGROUND: Children experiencing unfavorable family circumstances have an increased risk of developing externalizing symptoms. The present study examines the direct, indirect and total effects of family adversity, parental psychopathology, and positive and negative parenting practices on symptoms of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in children with ADHD. METHODS: Data from 555 children (M = 8.9 years old, 80.5% boys) who participated in a multicenter study on the treatment of ADHD (ESCAschool) were analyzed using structural equation modeling (SEM). RESULTS: The SEM analyses revealed that (a) family adversity and parental psychopathology are associated with both child ADHD and ODD symptoms while negative parenting practices are only related to child ODD symptoms; (b) family adversity is only indirectly associated with child ADHD and ODD symptoms, via parental psychopathology and negative parenting practices; (c) the detrimental effect of negative parenting practices on child ADHD and ODD symptoms is stronger in girls than in boys (multi-sample SEM); (d) there are no significant associations between positive parenting practices and child ADHD or ODD symptoms. CONCLUSIONS: Family adversity, parental psychopathology, and negative parenting practices should be routinely assessed by clinicians and considered in treatment planning. Trial registration (18th December 2015): German Clinical Trials Register (DRKS) DRKS00008973.

Multimodal treatment efficacy differs in dependence of core symptom profiles in adult Attention-Deficit/Hyperactivity Disorder: An analysis of the randomized controlled COMPAS trial.

There is broad consensus that to improve the treatment of adult Attention-Deficit/Hyperactivity Disorder (ADHD), the various therapy options need to be tailored more precisely to the individual patient's needs and specific symptoms. This post-hoc analysis evaluates the multimodal effects of first-line medication (methylphenidate [MPH] vs placebo [PLB]) and psychotherapeutic (group psychotherapy [GPT] vs clinical management [CM]) treatments on the ADHD core symptoms inattention, hyperactivity and impulsivity. For the two-by-two factorial, observer-blinded, multicenter, randomized controlled Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS; ISRCTN54096201), 419 outpatients with ADHD were considered for analysis. ADHD symptoms were assessed by blind observer-rated and patient-rated Conners Adult ADHD Rating Scales before treatment (T1), 13 weeks (T2) and 26 weeks (T3) after T1, at treatment completion after 52 weeks (T4), and at follow-up (130 weeks, T5). MPH was superior to PLB in improving symptoms of inattention at almost all endpoints (observer-rated T2, T3, T4, T5; patient-rated T2, T3, T4), while a significant decrease in hyperactivity and impulsivity was at first found after 6 months of treatment. CM compared to GPT decreased inattention and impulsivity in the early treatment phase only (observer-rated T2, patient-rated T2, T3). In conclusion, while MPH seems to have a direct and sustained effect on inattention, premature medication discontinuation should particularly be avoided in patients with hyperactive-impulsive symptoms. Also, especially in high inattention and/or impulsivity presentations, initial individual patient management might be beneficial. Consequently, considering individual core symptom profiles may enhance the efficacy of treatments in adult ADHD.

ADHD symptom profiles, intermittent explosive disorder, adverse childhood experiences, and internalizing/externalizing problems in young offenders.

Attention-deficit/hyperactivity disorder (ADHD) and co-existing psychiatric/psychological impairments as well as adverse childhood experiences (ACEs) are common among young offenders. Research on their associations is of major importance for early intervention and crime prevention. Intermittent explosive disorder (IED) warrants specific consideration in this regard. To gain sophisticated insights into the occurrence and associations of ADHD, IED, ACEs, and further psychiatric/psychological impairments in young (male and female) offenders, we used latent profile analysis (LPA) to empirically derive subtypes among 156 young offenders who were at an early stage of crime development based on their self-reported ADHD symptoms, and combined those with the presence of IED. We found four distinct ADHD subtypes that differed rather quantitatively than qualitatively (very low, low, moderate, and severe symptomatology). Additional IED, ACEs, and further internalizing and externalizing problems were found most frequently in the severe ADHD subtype. Furthermore, females were over-represented in the severe ADHD subtype. Finally, ACEs predicted high ADHD symptomatology with co-existing IED, but not without IED. Because ACEs were positively associated with the occurrence of ADHD/IED and ADHD is one important risk factor for on-going criminal behaviors, our findings highlight the need for early identification of ACEs and ADHD/IED in young offenders to identify those adolescents who are at increased risk for long-lasting criminal careers. Furthermore, they contribute to the debate about how to best conceptualize ADHD regarding further emotional and behavioral disturbances.

Age at school entry and reported symptoms of attention-deficit/hyperactivity in first graders: results of the prospective cohort study ikidS.

Young age at school entry (ASE) is related to attention-deficit/hyperactivity disorder in higher grades. The reason for this association is unclear, but medical oversupply and stress-related factors are discussed. We aimed to investigate whether ASE is associated with reported symptoms of attention-deficit/hyperactivity (ADH) already in first grade. Data of a population-based prospective cohort study (N = 2003; Mainz-Bingen region; Rhineland-Palatinate; Germany) with baseline assessments prior to school entry and two follow-ups during first grade were analysed. ADH symptoms were assessed by parent and teacher versions of the Strengths and Difficulties Questionnaire. Associations between ASE and scores of the hyperactivity/inattention subscale (range 0-10) were investigated by regression analysis and adjusted for potential confounders and baseline symptoms prior to school entry. In total, 1633 children (52% boys, mean ASE 6.5 years) were included. There were no relationships between ASE and parent-reported scores of the hyperactivity/inattention subscale prior to school entry and 3 months thereafter. However, at the end of first grade, ASE was negatively associated with the hyperactivity/inattention subscale in parent (- 0.7 subscale points per year ASE, standard error = 0.16, p < 0.0001) and teacher reports (- 1.2 subscale points per year ASE, standard error = 0.25, p < 0.0001). This ASE effect appeared more pronounced in girls than in boys. Young ASE is related to more reported symptoms of ADH at the end of first grade, but not before. The evolvement of this effect during first grade may be a clue to ASE-related stress factors.

Reasons for admission and variance of body weight at referral in female inpatients with anorexia nervosa in Germany.

BACKGROUND: Body mass index (BMI) at hospital admission in patients with anorexia nervosa (AN) represents a prognostic marker for mortality, chronicity and future body weight. The current study focused on the associations between BMI standard deviation score (BMI-SDS) at admission and reasons for seeking inpatient treatment. Further interest was given to the relationship between premorbid weight and weight at admission, as well as the effect of both weight at referral and reasons for admission on treatment outcome. METHODS: Data ascertained in the German Register of Children and Adolescents with AN were analysed to assess the parental and patient overlap for 23 predefined reasons for admission, using factor analyses and regressions models. RESULTS: Complete parent-patient data sets were available for 360 patients out of 769. The highest consensus rates between parents and patients were obtained for weight and eating behavior related reasons and hyperactivity. Based on factor analysis, four factors emerged. Premorbid BMI-SDS, age and 'low body weight' as stated by patients or parents explained almost 40% of the variance of the BMI-SDS at admission. CONCLUSIONS: Results underscore the relevance of age and premorbid BMI for BMI at admission. Only single reasons for admission explained further variance, with 'low body weight' having the largest effect. Approximately 40% of the variance of BMI-SDS was explained. For the first time, the effect of premorbid BMI for BMI at admission was robustly demonstrated in a multicenter study. Of the variance in BMI-SDS at discharge, our model could explain 37%, with reasons for admission having a small effect. Further investigation of the reasons for admission would be worthwhile to improve treatment and prognosis.

Disentangling symptoms of externalizing disorders in children using multiple measures and informants.

The trait impulsivity theory suggests that a single, highly heritable externalizing liability factor, expressed as temperamental trait impulsivity, represents the core vulnerability for externalizing disorders. The present study sought to test the application of latent factor models derived from this theory to a clinical sample of children. Participants were 474 German children (age 6-12 years, 81% male) with symptoms of attention-deficit/hyperactivity disorder and externalizing behavior problems participating in an ongoing multicenter intervention study. Using confirmatory factor analyses (CFA) and exploratory structural equation modeling (ESEM), we evaluated several factor models of externalizing spectrum disorders (unidimensional; first-order correlated factors; higher-order factor; fully symmetrical bifactor; bifactor S-1 model). Furthermore, we assessed our prevailing factor models for measurement invariance across raters (clinicians, parents, teachers) and assessment modes (interview, questionnaires). While both CFA and ESEM approaches provided valuable insights into the multidimensionality, ESEM solutions were generally superior since they showed a substantially better model fit and less biased factor loadings. Among the models tested, the bifactor S-1 CFA/ESEM models, with a general hyperactivity-impulsivity reference factor, displayed a statistically sound factor structure and allowed for straightforward interpretability. Furthermore, these models showed the same organization of factors and loading patterns, but not equivalent item thresholds across raters and assessment modes, highlighting cross-situational variability in child behavior. Our findings are consistent with the assumption of the trait impulsivity theory that a common trait, presented as hyperactivity-impulsivity symptoms, underlies all externalizing disorders. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Systematic review of transdermal treatment options in attention-deficit/hyperactivity disorder: implications for use in adult patients.

BACKGROUND: Adults with attention-deficit/hyperactivity disorder (ADHD) often face delays in diagnosis and remain untreated, despite significant negative impacts. To evaluate the safety and efficacy of transdermal treatment options in children, adolescents, and adults, a systematic literature review was conducted, with a focus on the implications of transdermal therapies for ADHD in adults. METHODS: A MEDLINE/Embase/BIOSIS/SCOPUS database search was conducted December 4, 2019, for English-language articles of interventional clinical trials using transdermal formulations for the treatment of ADHD without publication date limit. Assessed outcomes included efficacy, safety, adherence, abuse potential, cost efficacy, and health-related quality of life. RESULTS: Of 23 eligible publications, 18 were in children or adolescents (n = 1699; range 23-305), and 5 in adults (n = 274; range 14-90); all included methylphenidate transdermal system (MTS). All seven pediatric publications reporting change in ADHD symptomology from baseline reported a significant improvement with MTS treatment. Similarly, in three adult publications, ADHD symptoms improved significantly with MTS treatment. Safety findings in pediatric and adult studies were comparable; the most frequently reported treatment-emergent adverse events (TEAEs), namely, headache, decreased appetite, and insomnia, were reported in 13/16 (81%) of publications reporting specific TEAEs. MTS-related dermal reactions were mostly mild and transient. Discontinuation due to dermal reactions was reported in 10 studies (range 0%-7.1% [1 of 14 patients]). MTS compliance was high when assessed (97%-99%). CONCLUSIONS: Transdermal therapies provide a useful treatment formulation for ADHD. Studies of MTS and other transdermal formulations, such as amphetamine, in adult patients are needed in this underserved population.

Effectiveness and safety of dexamphetamine sulfate (Attentin®) in the routine treatment of children and adolescents with ADHD: results from a 12-month non-interventional study.

BACKGROUND: Randomized controlled trials have shown that dexamphetamine sulfate (DEX) is efficacious in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents; however, data on the effectiveness and safety of DEX in routine practice are scarce. OBJECTIVE: This study investigated the long-term effectiveness and safety of Attentin® (immediate-release DEX) in children and adolescents with ADHD in routine practice. METHODS: ATTENTION was a multicenter, prospective, observational, non-interventional study that enrolled pediatric patients with ADHD (aged 6-17 years) with a clinically inadequate response to previous methylphenidate (MPH) treatment. Patients were assessed at baseline and two follow-up visits after approx. 6 and 12 months of DEX treatment. The primary endpoint was the investigator-rated ADHD rating scale IV (ADHD-RS-IV) total score change from baseline to the first follow-up visit. RESULTS: The study enrolled 140 patients (mean age: 11.2 years). Significant reductions in ADHD-RS-IV total scores were observed in the titration phase and were maintained up to the second follow-up visit. The mean ADHD-RS-IV total score change from baseline to the first follow-up visit was -11.9 (27.1 vs. 13.4, p < .001). Beneficial effects of DEX were observed on both ADHD-RS-IV subscales ('hyperactivity/impulsivity' and 'inattention') and in both children and adolescents. Clinical response, defined as a reduction in the ADHD-RS-IV total score of at least 30% at the first follow-up visit, was observed in 78.1% of patients. Patients reported an average onset of action of 36.2 minutes and an average duration of action of 6.5 hours after intake of the first dose of DEX in the morning. DEX was well tolerated. Small significant increases in mean systolic and diastolic blood pressure compared to baseline were observed. CONCLUSIONS: Attentin® is an effective and well-tolerated long-term treatment for pediatric ADHD patients with a clinically inadequate response to previous MPH treatment.

Herbal High: Substance-Induced Psychosis after Consumption of Seeds of the Hawaiian Baby Woodrose.

Seeds of the Hawaiian Baby Woodrose (HBWR, Argyreia nervosa) are known as "legal or herbal highs" and can be easily purchased online in Germany. They contain various ergot alkaloids, including lysergic acid amide (LSA), which is chemically related to lysergic acid diethylamide (LSD). Pharmacological data are limited but suggest that LSA-concentration in HBWR seeds is highly variable, and that adverse psychiatric and somatic effects are not related to LSA-dosage. Anecdotal, mostly cross-sectional clinical case reports describe spontaneous remission of intoxication-related somatic and psychiatric symptoms as well as intoxication-related death. Treatment recommendations for LSA-induced psychiatric syndromes are not available. We report here on the clinical course and treatment of a drug-induced psychosis after consumption of HBWR seeds. The adolescent had consumed HBWR seeds once before without suffering any negative effects.

EEG Data Quality: Determinants and Impact in a Multicenter Study of Children, Adolescents, and Adults with Attention-Deficit/Hyperactivity Disorder (ADHD).

Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (ntotal = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.

The association between adverse childhood experiences and mental health problems in young offenders.

High rates of adverse childhood experiences (ACEs, e.g., abuse and neglect) have been found in young offenders. Furthermore, ACEs seem to increase the risk of developing relevant mental health problems, in non-offending juveniles and adults. However, this association has only seldomly been addressed in offending juveniles and young adults. The present study aimed at evaluating the prevalence of ACEs and mental health problems as well as their association within a sample of male and female young offenders. Altogether, 161 adolescent and young adult offenders (16.8% females) from the youth detention center Worms (Germany) filled out questionnaires concerning ACEs and mental health problems with a focus on attention-deficit/hyperactivity disorder and intermittent explosive disorder. Considerable rates of mental health problems were found, e.g., a prevalence of 35.9% was found for intermittent explosive disorder. Furthermore, a greater proportion of the female offenders fell into the clinically significant category for somatic complaints, anxiety/depression, and attention problems than the male offenders. Female young offenders also reported more frequently about all forms of ACEs compared to the male offenders. Latent class analysis defined three subtypes of young offenders depending on their individual ACE patterns: (1) low ACEs, (2) mainly neglectful ACEs, and (3) multiple ACEs. ACEs were significantly associated with the occurrence of both internalizing and externalizing mental health disturbances, with the multiple-ACE subtype being most likely to report about significant mental health problems. The results of the present study point towards the relevance to routinely assess ACEs in young offenders to identify possible precursors of mental health problems and of future criminal behaviors.

Functional impairment outcomes in clinical trials of different ADHD medications: post hoc responder analyses and baseline subgroup analyses.

Several recent phase 3 clinical trials of attention-deficit/hyperactivity disorder (ADHD) medications have used the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P). Here, we assess WFIRS-P response in individual patients in two pivotal trials of lisdexamfetamine dimesylate (LDX) and guanfacine extended release (GXR). We also analysed pooled WFIRS-P data from seven phase 3 studies of ADHD medications to shed light on factors associated with baseline functional impairment. The proportion of patients with a change in WFIRS-P score that exceeded the minimal important difference (MID) criteria for response was greater for LDX than placebo in the Family, Learning and School, and Risky Activities domains, and was greater for GXR than placebo in the Social Activities, Learning and School, and Family domains. Responders had significantly worse baseline scores in all WFIRS-P domains (all p < 0.001) than non-responders. In the pooled analyses, baseline WFIRS-P scores in all domains were significantly worse in participants with oppositional defiant disorder (ODD) than in those without ODD. Having combined type or hyperactive-impulsive type ADHD, being enrolled into a study in Europe, being male and being younger also had modest negative effects on baseline WFIRS-P scores. The present analysis of WFIRS-P response shows that previously reported group-level improvements in WFIRS-P functional impairment score translated into clinically relevant improvements in many individual participants. Functional impairment is a diverse and subjective construct that is influenced by multiple factors. Optimal management of individuals with ADHD should involve monitoring improvements in functioning and quality of life, as well as symptomatic improvement.

Safety Profile of Methylphenidate Under Long-Term Treatment in Adult ADHD Patients - Results of the COMPAS Study.

INTRODUCTION: The Comparison of Methylphenidate and Psychotherapy in adult ADHD Study (COMPAS) was a prospective, randomized multicenter clinical trial, comparing methylphenidate (MPH) with placebo (PLAC) in combination with cognitive behavioral group psychotherapy (GPT) or individual clinical management (CM) over the period of 1 year. Here, we report results on treatment safety. METHODS: MPH and PLAC were flexibly dosed. Among 433 randomized patients, adverse events (AEs) were documented and analyzed on an "as received" basis during week 0-52. Electrocardiogram data were recorded at baseline and week 24. RESULTS: Comparing 205 patients who received ≥1 dose of MPH with 209 patients who received PLAC, AEs occurring significantly more frequently in the MPH group were decreased appetite (22 vs. 3.8%), dry mouth (15 vs. 4.8%), palpitations (13 vs. 3.3%), gastrointestinal infection (11 vs. 4.8%), agitation (11 vs. 3.3%), restlessness (10 vs. 2.9%), hyperhidrosis, tachycardia, weight decrease (all 6.3 vs. 1.9%), depressive symptom, influenza (both 4.9 vs. 1.0%), and acute tonsillitis (4.4 vs. 0.5%). Syncope occurred significantly more often in the PLAC group (2.4 vs. 0%). Clinically relevant ECG changes occurred very rarely in both groups. Serious AEs were rare and without a significant group difference. The comparison of 206 patients treated with GPT versus 209 patients who received CM revealed no major differences. Serious AE classified as psychiatric occurred in 5 cases in the CM group and in 1 case in the GPT group. CONCLUSION: In this so far longest-running clinical trial, methylphenidate treatment was safe and well-tolerated.

Toward a Dimensional Assessment of Externalizing Disorders in Children: Reliability and Validity of a Semi-Structured Parent Interview.

OBJECTIVE: This study assesses the reliability and validity of the DSM-5-based, semi-structured Clinical Parent Interview for Externalizing Disorders in Children and Adolescents (ILF-EXTERNAL). METHOD: Participant data were drawn from the ongoing ESCAschool intervention study. The ILF-EXTERNAL was evaluated in a clinical sample of 474 children and adolescents (aged 6-12 years, 92 females) with symptoms of attention-deficit/hyperactivity disorder (ADHD). To obtain interrater reliability, the one-way random-effects, absolute agreement models of the intraclass correlation (ICC) for single ICC(1,1) and average measurements ICC(1,3) were computed between the interviewers and two independent raters for 45 randomly selected interviews involving ten interviewers. Overall agreement on DSM-5 diagnoses was assessed using Fleiss' kappa. Further analyses evaluated internal consistencies, item-total correlations as well as correlations between symptom severity and the degree of functional impairment. Additionally, parents completed the German version of the Child Behavior Checklist (CBCL) and two DSM-5-based parent questionnaires for the assessment of ADHD symptoms and symptoms of disruptive behavior disorders (FBB-ADHS; FBB-SSV), which were used to evaluate convergent and divergent validity. RESULTS: ICC coefficients demonstrated very good to excellent interrater reliability on the item and scale level of the ILF-EXTERNAL [scale level: ICC(1,1) = 0.83-0.95; ICC(1,3) = 0.94-0.98]. Overall kappa agreement on DSM-5 diagnoses was substantial to almost perfect for most disorders (0.38 ≤ κ ≤ 0.94). With some exceptions, internal consistencies (0.60 ≤ α ≤ 0.86) and item-total correlations (0.21 ≤ r it ≤ 0.71) were generally satisfactory to good. Furthermore, higher symptom severity was associated with a higher degree of functional impairment. The evaluation of convergent validity revealed positive results regarding clinical judgment and parent ratings (FBB-ADHS; FBB-SSV). Correlations between the ILF-EXTERNAL scales and the CBCL Externalizing Problems were moderate to high. Finally, the ILF-EXTERNAL scales were significantly more strongly associated with the CBCL Externalizing Problems than with the Internalizing Problems, indicating divergent validity. CONCLUSION: In clinically referred, school-age children, the ILF-EXTERNAL demonstrates sound psychometric properties. The ILF-EXTERNAL is a promising clinical interview and contributes to high-quality diagnostics of externalizing disorders in children and adolescents.

Efficacy of Guanfacine Extended Release in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder and Comorbid Oppositional Defiant Disorder.

OBJECTIVE: To assess the efficacy of the non-stimulant guanfacine extended release (GXR) on attention-deficit/hyperactivity disorder (ADHD) symptoms in children and adolescents, with and without comorbid oppositional defiant disorder (ODD). METHODS: Data were derived from 4 phase 3, randomized, placebo-controlled trials of dose-optimized GXR monotherapy, in which at least 10% of participants had a diagnosis of comorbid ODD. SPD503-312 and SPD503-316 were 10- to 13-week studies of GXR (1-7 mg/d). SPD503-314 and SPD503-307 were 8-week studies of GXR (1-4 mg/d). Efficacy was assessed using the ADHD Rating Scale IV (ADHD-RS-IV) total scores. RESULTS: In total, 1,084 participants were included (SPD503-312 and SPD503-316, n = 537; SPD503-314, n = 333; and SPD503-307, n = 214). GXR was associated with significant improvements in ADHD core symptoms at endpoint in participants with and without ODD (p < 0.01 in all studies). Placebo-adjusted least-squares mean (95% confidence interval) changes from baseline to endpoint in the ADHD-RS-IV total scores in participants with and without ODD were -8.6 (-14.4, -2.8) and -7.3 (-9.5, -5.0) in the pooled data from SPD503-312 and SPD503-316, -12.6 (-19.6, -5.7) and -8.7 (-11.8, -5.5) in SPD503-314, and -12.7 (-17.3, -8.1) and -11.8 (-19.3, -4.4) in SPD503-307, respectively. The corresponding effect sizes were 0.688 and 0.598 in SPD503-312 and SPD503-316, 0.876 and 0.729 in SPD503-314, and 0.962 and 0.842 in SPD503-307. CONCLUSION: The findings demonstrate the efficacy of GXR for treating ADHD in children and adolescents with comorbid ODD.

Long-term Effects of Multimodal Treatment on Adult Attention-Deficit/Hyperactivity Disorder Symptoms: Follow-up Analysis of the COMPAS Trial.

Importance: Knowledge about the long-term effects of multimodal treatment in adult attention-deficit/hyperactivity disorder (ADHD) is much needed. Objective: To evaluate the long-term efficacy of multimodal treatment for adult ADHD. Design, Setting, and Participants: This observer-masked, 1.5-year follow-up of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a prospective, multicenter randomized clinical trial, compared cognitive behavioral group psychotherapy (GPT) with individual clinical management (CM) and methylphenidate (MPH) with placebo (2 × 2 factorial design). Recruitment started January 2007 and ended August 2010, and treatments were finalized in August 2011 with follow-up through March 2013. Overall, 433 adults with ADHD participated in the trial, and 256 (59.1%) participated in the follow-up assessment. Analysis began in November 2013 and was completed in February 2018. Interventions: After 1-year treatment with GPT or CM and MPH or placebo, no further treatment restrictions were imposed. Main Outcomes and Measures: The primary outcome was change in the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score from baseline to follow-up. Secondary outcomes included further ADHD rating scale scores, observer-masked ratings of the Clinical Global Impression scale, and self-ratings of depression on the Beck Depression Inventory. Results: At follow-up, 256 of 433 randomized patients (baseline measured in 419 individuals) participated. Of the 256 patients participating in follow-up, the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score was assessed for 251; the mean (SD) baseline age was 36.3 (10.1) years; 125 patients (49.8%) were men; and the sample was well-balanced with respect to prior randomization (GPT and MPH: 64 of 107; GPT and placebo: 67 of 109; CM and MPH: 70 of 110; and CM and placebo: 55 of 107). At baseline, the all-group mean ADHD Index of Conners Adult ADHD Rating Scale score was 20.6, which improved to adjusted means of 14.2 for the GPT arm and 14.7 for the CM arm at follow-up with no significant difference between groups (difference, -0.5; 95% CI, -1.9 to 0.9; P = .48). The adjusted mean decreased to 13.8 for the MPH arm and 15.2 for the placebo arm (difference, -1.4; 95% CI, -2.8 to -0.1; P = .04). As in the core study, MPH was associated with a larger reduction in symptoms than placebo at follow-up. These results remained unchanged when accounting for MPH intake at follow-up. Compared with participants in the CM arm, patients who participated in group psychotherapy were associated with less severe symptoms as measured by the self-reported ADHD Symptoms Total Score according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) of Conners Adult ADHD Rating Scale (AMD, -2.1; 95% CI, -4.2 to -0.1; P = .04) and in the subscale of reducing pure hyperactive symptoms, measured via the Diagnostic Checklist for the diagnosis of ADHD in adults (AMD, -1.3; 95% CI, -2.8 to 0.1; P = .08). Regarding the Clinical Global Impression scale assessment of effectiveness, the difference between GPT and CM remained significant at follow-up (odds ratio, 1.63; 95% CI, 1.03-2.59; P = .04). No differences were found for any comparison concerning depression as measured with the Beck Depression Inventory. Conclusions and Relevance: Results from COMPAS demonstrate a maintained improvement in ADHD symptoms for adults 1.5 years after the end of a 52-week controlled multimodal treatment period. The results indicate that MPH treatment combined with GPT or CM provides a benefit lasting 1.5 years. Confirming the results of the core study, GPT was not associated with better results regarding the primary outcome compared with CM. Trial Registration: isrctn.org Identifier: ISRCTN54096201.