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.

[Epidemiology, diagnostics and treatment of attention deficit-hyperactivity disorder (ADHD) in advanced age]. / Epidemiologie, Diagnostik und Therapie der Aufmerksamkeitsdefizit-Hyperaktivitäts-Störung (ADHS) im höheren Lebensalter.

Current studies demonstrate a comparably high prevalence of attention deficit-hyperactivity disorder (ADHD) in advanced age. Older people affected by ADHD suffer from a severe burden of psychiatric and somatic comorbidities as well as substantial impairment of social functioning and subjective well-being. The diagnostic differentiation from neurodegenerative diseases is particularly difficult in this age group. This narrative review summarizes the current knowledge about the epidemiology of ADHD in advanced age and possible relationships between ADHD and the risk for neurodegeneration. Furthermore, recommendations for diagnostics and treatment options of ADHD in advanced age are presented.

Validation of the German Version of the Mind Excessively Wandering Scale (MEWS-G).

Increasing evidence shows that unintentional mind wandering is linked to Attention Deficit Hyperactivity Disorder (ADHD) and that its frequency contributes to symptom severity and functional impairment in ADHD. However, empirical data on mind wandering in adult ADHD are still scarce, and a validated scale to assess mind wandering in German adult ADHD patients is lacking. The primary aim of this study is to assess the psychometric properties of the German version of the recently published Mind Excessively Wandering Scale (MEWS-G) in terms of factorial structure and factor stability, internal consistency and construct validity. Analyses were performed in 128 adults with ADHD, clinical and healthy controls. As described for the original English 15-item version of the scale, we found lowest item-total-correlations for items 6, 10 and 14 with item-total correlation of all: 0.54/ADHD: 0.32 (item 6), all: 0.55/ADHD: 0.39 (item 10) and all: 0.11/ADHD: -0.04 (item 14). Item-total correlations for the remaining items were 0.65-0.86 and Cronbach Alpha was 0.96 indicating good internal consistency of the 12-item version of scale, on which we based all further analyses. Principal component analysis indicated a one- and two- factorial scale structure respectively explaining 71.7 % and 78.7 % of variance. Both factors showed good stability with lower stability of the factor-2 solution if sample size was reduced. The two-factorial solution also had many cross-loadings and a strong correlation of both factors in confirmatory factorial analysis (rf1f2 = 0.87). It probably describes related and interdependent, but not distinct facets of mind wandering, which strongly argues for the one factorial structure of the scale. Mean MEWS-G score in ADHD was 23.77 ± 7.85 compared to 7.64 ± 7.27 in controls (p < .0001). According to ROC, the optimal cut-off point to discriminate ADHD and controls is at MEWS-G score = 13. On the symptom level, MEWS-G score was correlated with ADHD, depressive and total psychiatric symptom scores, on the personality level with neuroticsm and negatively with conscientiousness and on the functional level with social interaction difficulties and impaired self-efficacy. In summary, our study shows that MEWS-G is a reliable, valid instrument to assess spontaneous mind wandering in adult ADHD and to discriminate between ADHD and controls.

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.

Does helping mothers in multigenerational ADHD also help children in the long run? 2-year follow-up from baseline of the AIMAC randomized controlled multicentre trial.

ADHD often affects multiple generations in a family. Previous studies suggested that children with ADHD benefit less from therapy if parents are also affected, since ADHD symptoms interfere with treatment implementation. This two-group randomised controlled trial examined whether targeting maternal ADHD boosts the efficacy of parent-child training (PCT) for the child's ADHD. Here, we report follow-up results 2 years from baseline. Mothers of 144 mother-child dyads (ADHD according to DSM-IV) were examined for eligibility (T1) and randomised to 12 weeks of intensive multimodal treatment comprising pharmacotherapy and DBT-based cognitive behavioural group psychotherapy (TG, n = 77) or clinical management comprising non-specific counselling (CG, n = 67) for Step 1 (concluded by T2). Subsequently, all dyads participated in 12 weekly PCT sessions for Step 2 (concluded by T3). In Step 3, participants received maintenance treatments for 6 months (concluded by T4). At 24 months after baseline (T5), we performed follow-up assessments. The primary endpoint was child ADHD/ODD score (observer blind rating). Outcomes at T5 were evaluated using ANCOVA. Assessments from 101 children and 95 mothers were available at T5. Adjusted means (m) of ADHD/ODD symptoms (range 0-26) in children did not differ between TG and CG (mean difference = 1.0; 95% CI 1.2-3.1). The maternal advantage of TG over CG on the CAARS-O:L ADHD index (range 0-36) disappeared at T5 (mean difference = 0.2; 95% CI - 2.3 to 2.6). Sensitivity analyses controlling for medication and significant predictors of follow-up participation showed unchanged outcomes. Within-group outcomes remained improved from baseline. At the 24-month follow-up, TG and CG converged. The superiority of intensive treatment regarding maternal symptoms disappeared. In general, cross-generational treatment seems to be effective in the long term. (BMBF grant 01GV0605; registration ISRCTN73911400).

A multicentre randomized controlled trial on trans-generational attention deficit/hyperactivity disorder (ADHD) in mothers and children (AIMAC): an exploratory analysis of predictors and moderators of treatment outcome.

OBJECTIVE: We examined predictors and moderators of treatment outcome in mothers and children diagnosed with ADHD in a large multicentre RCT. METHOD: In total, 144 mother-child dyads with ADHD were randomly assigned to either a maternal ADHD treatment (group psychotherapy and open methylphenidate medication, TG) or to a control treatment (individual counselling without psycho- or pharmacotherapy, CG). After maternal ADHD treatment, parent-child training (PCT) for all mother-child dyads was added. The final analysis set was based on 123 dyads with completed primary outcome assessments (TG: n = 67, CG: n = 56). The primary outcome was the change in each child's externalizing symptoms. Multiple linear regression analyses were performed. RESULTS: The severity of the child's externalizing problem behaviour in the family at baseline predicted more externalizing symptoms in the child after PCT, independent of maternal treatment. When mothers had a comorbid depression, TG children showed more externalizing symptoms after PCT than CG children of depressive mothers. No differences between the treatment arms were seen in the mothers without comorbid depression. CONCLUSIONS: Severely impaired mothers with ADHD and depressive disorder are likely to need additional disorder-specific treatment for their comorbid psychiatric disorders to effectively transfer the contents of the PCT to the home situation (CCTISRCTN73911400).

Sequential treatment of ADHD in mother and child (AIMAC study): importance of the treatment phases for intervention success in a randomized trial.

BACKGROUND: The efficacy of parent-child training (PCT) regarding child symptoms may be reduced if the mother has attention-deficit/hyperactivity disorder (ADHD). The AIMAC study (ADHD in Mothers and Children) aimed to compensate for the deteriorating effect of parental psychopathology by treating the mother (Step 1) before the beginning of PCT (Step 2). This secondary analysis was particularly concerned with the additional effect of the Step 2 PCT on child symptoms after the Step 1 treatment. METHODS: The analysis included 143 mothers and children (aged 6-12 years) both diagnosed with ADHD. The study design was a two-stage, two-arm parallel group trial (Step 1 treatment group [TG]: intensive treatment of the mother including psychotherapy and pharmacotherapy; Step 1 control group [CG]: supportive counseling only for mother; Step 2 TG and CG: PCT). Single- and multi-group analyses with piecewise linear latent growth curve models were applied to test for the effects of group and phase. Child symptoms (e.g., ADHD symptoms, disruptive behavior) were rated by three informants (blinded clinician, mother, teacher). RESULTS: Children in the TG showed a stronger improvement of their disruptive behavior as rated by mothers than those in the CG during Step 1 (Step 1: TG vs. CG). In the CG, according to reports of the blinded clinician and the mother, the reduction of children's disruptive behavior was stronger during Step 2 than during Step 1 (CG: Step 1 vs. Step 2). In the TG, improvement of child outcome did not differ across treatment steps (TG: Step 1 vs. Step 2). CONCLUSIONS: Intensive treatment of the mother including pharmacotherapy and psychotherapy may have small positive effects on the child's disruptive behavior. PCT may be a valid treatment option for children with ADHD regarding disruptive behavior, even if mothers are not intensively treated beforehand. TRIAL REGISTRATION: ISRCTN registry ISRCTN73911400 . Registered 29 March 2007.

Does the efficacy of parent-child training depend on maternal symptom improvement? Results from a randomized controlled trial on children and mothers both affected by attention-deficit/hyperactivity disorder (ADHD).

Multimodal treatment of children with ADHD often includes parent-child training (PCT). However, due to the high heritability, parents of children with ADHD are frequently also affected by the disorder, which is likely to constitute a significant barrier to successful treatment of the child. This secondary analysis of our randomized controlled multicentre AIMAC trial (ADHD in mothers and children) investigates whether children's outcomes following parent-child training in combination with maternal ADHD treatment depend on maternal symptom improvement. In a first step focusing on treatment of maternal ADHD, 144 mothers of mother-child dyads were randomized to multimodal ADHD treatment (group psychotherapy plus methylphenidate) or clinical management (mainly supportive counselling). After 12 weeks (T2), a 12-week PCT program (T2-T3) for all mother-child dyads was added to treat children's ADHD. Maternal symptomatology (CAARS-O:L; SCL-90-R) and children's externalizing symptoms (ADHD-ODD Scale, SDQ) were repeatedly assessed (T1 = baseline, T2, T3). Effects of changes in maternal symptomatology (T1-T2) on the change in children's symptom scores (T1-T3) were analysed using a general linear model, controlling for baseline scores, study centre, and maternal treatment group. 125 mother-child dyads were analysed. Mothers showed significant improvements in ADHD symptoms and overall psychopathology [CAARS-O:L ADHD index: mean - 3.54, SE 0.74 p < 0.0001; SCL-90-R Global Severity (GS): mean - 11.03, SE 3.90, p = 0.0056]. Although children's externalizing symptoms improved significantly (ADHD-ODD Scale: mean - 4.46, SE 0.58, p < 0.0001), maternal improvement had no effect on children's outcomes after Bonferroni-Holm correction for multiple testing. The findings do not support our hypothesis that children's outcomes following PCT for ADHD depend on maternal symptom improvements.Trial register CCT-ISRCTN73911400.

Nightmare frequency in adults with attention-deficit hyperactivity disorder.

Nightmare frequency in adult ADHD patients has not yet been studied systematically. In a sample of 65 patients, it could be shown that nightmare frequency was elevated in ADHD patients compared to a sample representative for Germany. Frequent nightmares (once a week or more often) were reported by 4.62 % of the patients and 1.77 % of the controls. This increase was neither explained by the increased dream recall in general nor by the presence of a comorbid mental disorder. Questions about nightmares should be included in the diagnostic procedures for ADHD patients, and it should be tested whether well-established nightmare treatment strategies like imagery rehearsal treatment might be beneficial to those patients with nightmares.

Does intensive multimodal treatment for maternal ADHD improve the efficacy of parent training for children with ADHD? A randomized controlled multicenter trial.

BACKGROUND: This is the first randomized controlled multicenter trial to evaluate the effect of two treatments of maternal attention-deficit hyperactivity disorder (ADHD) on response to parent-child training targeting children's external psychopathology. METHODS: Mother-child dyads (n = 144; ADHD according to DSM-IV; children: 73.5% males, mean age 9.4 years) from five specialized university outpatient units in Germany were centrally randomized to multimodal maternal ADHD treatment [group psychotherapy plus open methylphenidate medication; treatment group (TG): n = 77] or to clinical management [supportive counseling without psychotherapy or psychopharmacotherapy; control group (CG): n = 67]. After 12 weeks, the maternal ADHD treatment was supplemented by individual parent-child training for all dyads. The primary outcome was a change in the children's externalizing symptom scores (investigator blinded to the treatment assignment) from baseline to the end of the parent-child training 6 months later. Maintenance therapy continued for another 6 months. An intention-to-treat analysis was performed within a linear regression model, controlling for baseline and center after multiple imputations of missing values. RESULTS: Exactly, 206 dyads were assessed for eligibility, 144 were randomized, and 143 were analyzed (TG: n = 77; CG: n = 66). After 6 months, no significant between-group differences were found in change scores for children's externalizing symptoms (adjusted mean TG-mean CG=1.1, 95% confidence interval -0.5-2.7; p = .1854), although maternal psychopathology improved more in the TG. Children's externalizing symptom scores improved from a mean of 14.8 at baseline to 11.4 (TG) and 10.3 (CG) after 6 months and to 10.8 (TG) and 10.1 (CG) after 1 year. No severe harms related to study treatments were found, but adverse events were more frequent in TG mothers than in CG mothers. CONCLUSIONS: The response in children's externalizing psychopathology did not differ between maternal treatment groups. However, multimodal treatment was associated with more improvement in maternal ADHD. Child and maternal treatment gains were stable (CCT-ISRCTN73911400).

Impulsivity in relation to stress in patients with borderline personality disorder with and without co-occurring attention-deficit/hyperactivity disorder: an exploratory study.

Impulsivity is regarded as a key feature in borderline personality disorder (BPD). However, discrepancies in previous research indicate that the role of impulsivity in BPD is not yet fully understood. For example, state-dependent impulsivity in individuals with BPD may be related to co-occurring psychiatric conditions such as attention-deficit/hyperactivity disorder (ADHD) and to emotional states. We assessed self-reports of trait and state impulsivity and response inhibition before and after an experimental stress induction in 15 patients with BPD without ADHD, 15 patients with BPD and ADHD, 15 patients with ADHD, and 15 healthy participants. The patients in both BPD subgroups reported a stress-dependent increase of state impulsivity, which was not observed in the other groups. Response inhibition was impaired in the patients with BPD and ADHD but not in those without ADHD compared with the healthy participants. We suggest that stress levels and co-occurring ADHD should receive attention in future studies on impulsivity in BPD.

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).

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.

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.

Effects of 12-Week Methylphenidate Treatment on Neurometabolism in Adult Patients with ADHD: The First Double-Blind Placebo-Controlled MR Spectroscopy Study.

Attention deficit hyperactivity disorder (ADHD) is a frequent neurodevelopmental disorder that often persists into adulthood. Methylphenidate (MPH) is the first-line treatment for ADHD; however, despite its wide usage, little is known about its neurometabolic effects. Until now, no randomized and blinded clinical trials have been conducted addressing the neurometabolic signals of MPH administration in adults with ADHD. In the current study, the authors investigated how MPH intake and group psychotherapy (GPT) influence brain neurometabolism over the course of three months. The authors hypothesized a decrease in the anterior cingulate cortex (ACC) glutamate concentration following MPH administration. This study was part of a double-blind multicenter trial (Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS)) investigating the effects of MPH and GPT in patients with adult ADHD. Using single-voxel magnetic resonance spectroscopy (MRS) of the pregenual ACC and the left cerebellar hemisphere (CHL), we investigated the concentration of glutamate plus glutamine (Glx), N-acetyl-aspartate, creatine, total choline containing compounds, and myo-inositol in patients before and after 12 weeks of treatment. Neither MPH nor GPT significantly influenced the Glx concentration or any of the other metabolite concentrations in the ACC and CHL after 12 weeks. Therefore, contrary to the hypothesis, no change in the prefrontal Glx signal was detected after MPH treatment. Given that MRS does not differentiate between glutamate in the synaptic cleft and in neuronal tissue, MPH-induced down-regulation of glutamatergic neurotransmission in the ACC might only affect the concentration of glutamate in the synaptic cleft, while the general availability of glutamate in the respective neuronal tissue might be unaffected by MPH intake. The observed lack of any MPH-induced normalization in metabolite concentrations is less surprising, considering that the baseline sample did not significantly differ from a healthy control group. Future studies of other regions, such as the basal ganglia, and the use of novel methods, such as whole brain MRS and multimodal imaging approaches, are necessary.

Internalized stigma, anticipated discrimination and perceived public stigma in adults with ADHD.

The objective of this study is to assess internalized stigma, perceived public stigma, anticipated discrimination and their associations with demographic, psychiatric and psychosocial characteristics in adult ADHD. Stigmatization was assessed with the Internalized Stigma of Mental Illness Scale, the Questionnaire on Anticipated Discrimination and the Questionnaire on Public Stereotypes Perceived by Adults with ADHD. The sample comprised n = 104 adults with ADHD, of whom n = 24 (23.3%) reported high internalized stigma, n = 92 (88.5%) anticipated discrimination in daily life and n = 70 (69.3%) perceived public stigma. Internalized stigma and/or anticipated discrimination correlated with ADHD symptoms, psychological distress, self-esteem, functional impairment and quality of life and was associated with ADHD family history and employment status. Most frequently perceived stereotypes were doubts about the validity of ADHD as a mental disorder. Internalized stigma and anticipated discrimination are highly prevalent in adult ADHD and correlate with the burden of disease. ADHD is associated with characteristic public stereotypes, which are distinct from stereotypes related to other mental disorders. Stigmatization should be considered in the clinical management of adult ADHD and evaluated further in future studies.

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.

Sleep in adults with attention deficit hyperactivity disorder (ADHD) before and during treatment with methylphenidate: a controlled polysomnographic study.

STUDY OBJECTIVES: Sleep problems are frequently associated with childhood ADHD, as indicated by numerous polysomnographic investigations showing increased nocturnal movements, reduced sleep efficiency, and decreased percentage of REM sleep (although findings are not consistent over all studies). Data on objective and subjective sleep parameters in adults with ADHD are sparse, and to date the impact of stimulants, the most widely used pharmacological treatment for ADHD, on sleep in adults with ADHD has not been examined. Thus the objectives of our study were to assess objective and subjective sleep parameters in adults with ADHD and the impact of stimulant medication on sleep. DESIGN: Two-group comparison and open-label therapy study. PARTICIPANTS: We enrolled 34 nonmedicated patients with ADHD, of whom 24 were without current comorbid psychiatric disorders, and 34 sex- and gender-matched control subjects without current psychiatric disorders or psychotropic medication. INTERVENTIONS: Ten patients were treated with methylphenidate over > or =26 days with a mean daily dose of 36.7 +/- 11.2 mg. MEASUREMENTS: Polysomnographic recording over 2 consecutive nights as well as assessments of subjective sleep parameters were performed in all patients and controls before treatment and reassessed in those patients receiving methylphenidate. RESULTS: Compared to controls untreated patients showed increased nocturnal activity, reduced sleep efficiency, more nocturnal awakenings and reduced percentage of REM sleep. Treatment with methylphenidate resulted in increased sleep efficiency as well as a subjective feeling of improved restorative value of sleep. CONCLUSIONS: Sleep problems in patients with ADHD continue from childhood to adulthood, with similar objective sleep characteristics in adults and children with ADHD. Medication with methylphenidate appears to have beneficial effects on sleep parameters in adults with ADHD.

Cognitive MR spectroscopy of anterior cingulate cortex in ADHD: elevated choline signal correlates with slowed hit reaction times.

The anterior cingulate cortex (ACC) plays a major role in modulating executive control of attention. Here, 15 medication-nai ve patients with attention deficit/hyperactivity disorder (ADHD) and 10 carefully matched healthy controls were studied with 2D (1)H-magnetic resonance spectroscopic imaging (MRSI) of the ACC [Brodmann areas 24b'-c' and 32']. Attentional skills were assessed using the identical pairs version of the continuous performance task (CPT-IP). Analysis of regional brain spectra revealed a significantly increased signal of choline-containing compounds (Ch) in the ACC of ADHD patients (p<0.05). Across and within groups, the Ch signal showed high correlations with slowed hit reaction times on the CPT-IP. No group differences in N-acetyl-aspartate (NAA) and creatine (tCr) were detectable. The combination of performance deficits and elevated Ch levels in the ACC supports the hypothesis that subtle structural abnormalities underlie the functional alterations in ACC activation previously observed in ADHD patients.