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Attention Deficit Hyperactivity Disorder (ADHD) negatively impacts Quality of Life (QoL) in adults. Earlier studies on pharmacological treatment have shown short-term beneficial effects on QoL. No data are available on long-term effects on multimodal psychosocial and/or pharmacological interventions. 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 (Plac) (2 × 2 factorial design over a period of 52 weeks). Change of QoL was measured after three months of intensive treatment, after 26 weeks, and after one year of maintenance treatment, using the Quality of life enjoyment and satisfaction questionnaire (Q-LES-Q, eight subscales). A follow-up was performed 1.5 years after treatment completion. Q-LES-Q scores were analyzed descriptively (means and confidence intervals). A linear regression model was used to test for significant differences between the four treatment arms. The full analysis set comprised 419 patients. Q-LES-Q scores increased between baseline and the end of treatment across all Q-LES-Q subscales (with exception of stable scores in the physical health/activities subscale in the CM + Plac group) and remained stable improved at follow-up. Regression analyses did not show any significant differences between the four treatment conditions. COMPAS is the first study to demonstrate stable and long-term improvements of QoL after multimodal treatment regardless of medication with MPH or Placebo, and regardless of structured GPT or individual CM. Trial registration: ISRCTN54096201.

**Background.** Suicidal ideations (SI) are amongst the strongest predictors for suicide attempts, yet reliable prediction models for suicide risk are still lacking. One explanation for this is that endorsement and expression of SI are not uniform and may vary when indexed over time. Using intensive longitudinal assessments of SI with ecological momentary assessments (EMA), prior research identified five distinct subgroups that differed in mean SI severity and variability over time. **Methods.** We first aimed to replicate these results using latent profile analysis (LPA) on EMA data (5 assessments/day over 28 days: 34% response rate of all beeps completed) of 50 psychiatric patients (32 females, 64%, age *M*=35.26, *SD*=12.54). We then used longitudinal clustering (LC), an advanced statistical approach that considers the longitudinal, dynamic nature of EMA, to replicate the subgroups. **Results.** Using LPA, we replicated four of the five groups with somewhat different characterizations compared to prior findings. Using LC, we identified subgroups representing the nature of the observed SI better and showed more anticipated clinical characteristics. Among those, hopelessness and prior SI were most convincing, i.e., the subgroup with the least severe SI subgroup were characterized by least hopelessness and the most severe SI subgroup by more hopelessness. **Conclusion.** Applying LC to EMA collected from patients with SI allows to identify valid and reliable SI subgroups with more distinct clinical characteristics, an important step towards a better understanding of SI and basis for improving prediction and prevention.

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.

Obsessive compulsive disorder (OCD) has a large impact on the quality of life of patients. It often takes years to get the right diagnosis and to receive treatment. Therefore, biomarkers that could inform the diagnostic process and provide information on response or non-response for first line treatment approaches are urgently needed. The aim of this study was to analyze whether (1) heart rate (HR) and heart rate variability (HRV) markers of the autonomous nervous system could distinguish between healthy controls (HC) and patients suffering from OCD and (2) HRV parameters additionally yield useful information to separate therapy-responders from non-responders.A fifteen-minute resting state ECG (electrocardiogram) was recorded from 51 unmedicated OCD patients before treatment and 28 HC. The function of the autonomic nervous system was assessed by using parameters of the HRV. Clinical Global Impression (CGI) scores served as baseline and outcome parameters following three to six months of therapy (cognitive behavioral therapy n = 18, selective-serotonin-reuptake-inhibitor n = 11 or combination n = 22). Differences between patients and HC and responders and non-responders were identified using analysis of covariance (ANCOVAs). Predictive values were calculated following binary regression modelling and receiver operating characteristics (ROC).OCD patients revealed a significantly higher HR in comparison to HC. Although patients were thus characterized by increased sympathetic and decreased parasympathetic tone, treatment responders exhibited a larger High Frequency Power as a marker for increased parasympathetic activity at baseline. ROC-curves for OCD vs HC and R vs NR showed clinically relevant areas under curve (83%, 88% respectively).These results are in line with findings of increased sympathetic and decreased parasympathetic activity in OCD in comparison to healthy subjects. The findings further provide clinically useful information on treatment response in OCD.Results may facilitate the clinical use of electrophysiological markers in OCD.

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 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).

Background Multiple symptoms of suicide risk have been assessed based on visual and auditory information, including flattened affect, reduced movement, and slowed speech. Objective quantification of such symptomatology from novel data sources can increase the sensitivity, scalability, and timeliness of suicide risk assessment. Objective We aimed to examine measurements extracted from video interviews using open-source deep learning algorithms to quantify facial, vocal, and movement behaviors in relation to suicide risk severity in recently admitted patients following a suicide attempt. Methods We utilized video to quantify facial, vocal, and movement markers associated with mood, emotion, and motor functioning from a structured clinical conversation in 20 patients admitted to a psychiatric hospital following a suicide risk attempt. Measures were calculated using open-source deep learning algorithms for processing facial expressivity, head movement, and vocal characteristics. Derived digital measures of flattened affect, reduced movement, and slowed speech were compared to suicide risk with the Beck Scale for Suicide Ideation controlling for age and sex, using multiple linear regression. Results Suicide severity was associated with multiple visual and auditory markers, including speech prevalence (β=−0.68, P=.02, r2=0.40), overall expressivity (β=−0.46, P=.10, r2=0.27), and head movement measured as head pitch variability (β=−1.24, P=.006, r2=0.48) and head yaw variability (β=−0.54, P=.06, r2=0.32). Conclusions Digital measurements of facial affect, movement, and speech prevalence demonstrated strong effect sizes and linear associations with the severity of suicidal ideation.

BACKGROUND Multiple symptoms of suicide risk have been assessed based on visual and auditory information, including flattened affect, reduced movement, and slowed speech. Objective quantification of such symptomatology from novel data sources can increase the sensitivity, scalability, and timeliness of suicide risk assessment. OBJECTIVE We aimed to examine measurements extracted from video interviews using open-source deep learning algorithms to quantify facial, vocal, and movement behaviors in relation to suicide risk severity in recently admitted patients following a suicide attempt. METHODS We utilized video to quantify facial, vocal, and movement markers associated with mood, emotion, and motor functioning from a structured clinical conversation in 20 patients admitted to a psychiatric hospital following a suicide risk attempt. Measures were calculated using open-source deep learning algorithms for processing facial expressivity, head movement, and vocal characteristics. Derived digital measures of flattened affect, reduced movement, and slowed speech were compared to suicide risk with the Beck Scale for Suicide Ideation controlling for age and sex, using multiple linear regression. RESULTS Suicide severity was associated with multiple visual and auditory markers, including speech prevalence (β=−0.68, P=.02, r2=0.40), overall expressivity (β=−0.46, P=.10, r2=0.27), and head movement measured as head pitch variability (β=−1.24, P=.006, r2=0.48) and head yaw variability (β=−0.54, P=.06, r2=0.32). CONCLUSIONS Digital measurements of facial affect, movement, and speech prevalence demonstrated strong effect sizes and linear associations with the severity of suicidal ideation.

Annals of General Psychiatry 19, 55 (2020). doi:10.1186/s12991-020-00305-3, Published by BioMed Central, [S.l.]

BackgroundMultiple symptoms of suicide risk are assessed based on visual and auditory information including flattened affect, reduced movement, and slowed speech. Objective quantification of such symptomatology from novel data sources can increase the sensitivity, scalability, and timeliness of suicide risk assessment.MethodsIn the current study we utilized video to quantify facial, vocal, and movement markers associated with mood, emotion, and motor functioning from a structured clinical conversation in 20 patients admitted to a psychiatric hospital following a suicide risk attempt. Measures were calculated using open source deep learning algorithms for processing facial expressivity, head movement, and vocal characteristics. Derived digital measures of flattened affect, reduced movement, and slowed speech were compared to suicide severity using the Beck Suicide Scale (BSS), controlling for age and gender using multiple linear regression.ResultsSuicide severity was associated with multiple visual and auditory markers including speech prevalence (β = −0.68; P =.017, r2 =.40, overall expressivity (β = −0.46; P = 0.10, r2 =.27), and head movement measured as head pitch variability (β = −1.24; P =.006, r2 =.48) and head yaw variability (β = −0.54; p =.055, r2 =.32).ConclusionsDigital measurements of facial affect, movement, and speech prevalence demonstrated strong effect sizes and significant linear associations with severity of suicidal ideation.

Zusammenfassung. Fragestellung: Ziel der Untersuchung ist die Erhebung von Daten zu psychischen Belastungen und deren Behandlung bei Kindern und Jugendlichen mit Fragilem-X-Syndrom (FRX). Methodik: Die Ergebnisse basieren auf einer strukturierten, prospektiven, offenen, nichtinterventionellen, registerbasierten Beobachtungsstudie in Deutschland (EXPLAIN), im Rahmen derer an 11 Zentren 34 Patienten jünger als 18 Jahre mit einem genetisch gesicherten FRX eingeschlossen wurden. Ergebnisse: Jedes dritte Indexkind hatte ein ebenfalls unter FRX leidendes Geschwisterkind. Die Belastung mit neurologischen und psychischen Symptomen war insgesamt hoch, wobei ataktische Symptome, epileptische Anfälle und autistische Symptome nur bei den Kindern (< 14 Jahre) berichtet wurden. Nahezu alle erfassten psychischen Symptome und Störungen, insbesondere die expansiven Symptome, wurden mit entsprechenden Psychopharmaka behandelt. Darüber hinaus kamen oft logopädische, ergotherapeutische und heilpädagogische Maßnahmen zum Einsatz. Trotz der hohen Symptombelastung lebten 96.3 % der unter 14-Jährigen und immer noch 57.1 % der 14- bis 18-Jährigen im elterlichen Haushalt. Schlussfolgerungen: Aufgrund der hohen Belastung mit neurologischen und psychischen Symptomen sollte frühzeitig eine dem Alter entsprechende kinder- und jugendpsychiatrische und neurologische Diagnostik und Therapie erfolgen.

Key Points Question What are the long-term results of multimodal treatment for adult attention-deficit/hyperactivity disorder (ADHD) when comparing cognitive behavioral group psychotherapy (GPT) with individual clinical management (CM) in combination with either methylphenidate or placebo? Findings In this follow-up assessment of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a multicenter randomized clinical trial, 256 adults participated in follow-up 1.5 years after the intervention ended. The severity of ADHD symptoms improved in all 4 prior treatment groups, with no significant difference found between GPT and CM, but methylphenidate was associated with a larger improvement in symptoms compared with placebo. Meaning Results from the COMPAS trial demonstrate an improvement of ADHD symptoms over 1.5 years in adults with ADHD after 1 year of treatment with methylphenidate plus either GPT or CM., This follow-up assessment of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a multicenter randomized clinical trial, evaluates the long-term efficacy of multimodal treatment for attention-deficit/hyperactivity disorder (ADHD)., 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

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).

Objective: In the multicenter study Comparison of Methylphenidate and Psychotherapy in Adult ADHD (COMPAS), the efficacy of treatments has been primarily evaluated by observer-rated symptom change. Here, we additionally analyzed the patients’ subjective evaluation of therapy effects. Method: COMPAS compared ADHD-specific group therapy with unspecific clinical management with/without concomitant pharmacotherapy in a four-armed design. Evaluation through the patients’ retrospective perspective was performed after 1 year (post-treatment) and after another 1.5 years (follow-up). Results: In respect to patients’ subjective ratings, ADHD-specific group psychotherapy outperformed unspecific management post-treatment (z = 4.88, p < .0001) and at follow-up (z = 2.90, p = .004). Rank correlations with rater-based symptom change were small to moderate (post-treatment: rs = 0.28, follow-up: rs = 0.16). Conclusion: Therapy evaluation based on the patients’ perspective supports the concept of ADHD-specific group psycho...

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric condition that has been strongly associated with changes in sleep and circadian rhythms. Circadian rhythms are near 24-h cycles that are primarily generated by an endogenous circadian timekeeping system, encoded at the molecular level by a panel of clock genes. Stimulant and non-stimulant medication used in the management of ADHD has been shown to potentially impact on circadian processes and their behavioral outputs. In the current study, we have analyzed circadian rhythms in daily activity and sleep, and the circadian gene expression in a cohort of healthy controls (N = 22), ADHD participants not using ADHD-medication (N = 17), and participants with ADHD and current use of ADHD medication (N = 17). Rhythms of sleep/wake behavior were assessed via wrist-worn actigraphy, whilst rhythms of circadian gene expression were assessed ex-vivo in primary human-derived dermal fibroblast cultures. Behavioral data indicate that patients with ADHD using ADHD-medication have lower relative amplitudes of diurnal activity rhythms, lower sleep efficiency, more nocturnal activity but not more nocturnal wakenings than both controls and ADHD participants without medication. At the molecular level, there were alterations in the expression of PER2 and CRY1 between ADHD individuals with no medication compared to medicated ADHD patients or controls, whilst CLOCK expression was altered in patients with ADHD and current medication. Analysis of fibroblasts transfected with a BMAL1:luc reporter showed changes in the timing of the peak expression across the three groups. Taken together, these data support the contention that both ADHD and medication status impact on circadian processes.

Abstract. 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).

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. Open-Access-Publikationsfonds 2018

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).

Anliegen: Ziel der Untersuchung ist die Erhebung von Daten zu psychischen Belastungen und deren Behandlung beim fragilen X-Syndrom (FRX). Methode: Die Ergebnisse basieren auf einer Beobachtungsstudie (EXPLAIN). Ergebnisse: Die Belastung mit psychischen Symptomen war insgesamt hoch. Betroffene unter 18 Jahren wiesen mehr expansive, erwachsene Patienten dagegen mehr internalisierende Storungen auf. Trotz der hohen Symptombelastung lebten 90,6 % der unter 18-Jahrigen und immer noch 50 % der Erwachsenen im elterlichen Haushalt. Schlussfolgerungen: Aufgrund der hohen Belastung mit psychischen Symptomen sollte eine dem Alter entsprechende Diagnostik und Therapie erfolgen.

Contains fulltext : 152125.pdf (Publisher’s version ) (Open Access) The attention-deficit/hyperactivity disorder (ADHD) treatment literature has been focused on onset-of-effect and short-term effect size, with little exploration of ADHD symptoms upon medication discontinuation. The objective of this narrative review and analysis was to better understand the relapse of ADHD symptoms upon discontinuation of medication treatment in children, adolescents, and adults with ADHD who have responded to medication treatment and to explore differences among different medications in maintaining treatment response. Randomized withdrawal studies of dexmethylphenidate hydrochloride (d-MPH), methylphenidate modified-release (MPH-LA), lisdexamphetamine dimesylate (LDX), guanfacine extended-release (GXR), and atomoxetine (ATX) in both children/adolescents and adults with ADHD were reviewed. The percentage of relapse was significantly higher and the time-to-relapse significantly shorter with placebo compared to active treatment in patients who were previously stable on 5 weeks to 1 year of active treatment, suggesting clinically significant benefit with continued long-term pharmacotherapy. However, percentage of relapse at each time point studied after discontinuing stimulants and GXR appears substantially higher than observed when discontinuing ATX, suggesting longer maintenance of response after discontinuing ATX than after stimulants and GXR. Additionally, slope of relapse percentages over time appears to be more rapid with stimulants or GXR than with ATX. These differences in maintenance of response among ATX, GXR, and stimulants may reflect differences in mechanisms of action and persistence of the medication effect. Alternatively, they may be due to methodological differences, including study design and response/relapse definitions. Continued investigation is needed regarding factors that affect risk of symptom relapse upon discontinuation of pharmacotherapy.

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

Background As data on the phenotype, characteristics and management of patients with Fragile X Syndrome (FXS) are limited, we aimed to collect such data in Germany in experienced centres involved in the treatment of such patients. Methods EXPLAIN-FXS is a prospective observational (non- interventional) study (registry) performed between April 2013 and January 2016 at 18 sites in Germany. Requirements for patient participation included confirmed diagnosis of FXS by genetic testing (>200 CGG repeats) and written informed consent. Patients were followed for up to 2 years. Results Seventy- five patients (84.0 % males, mean age 16.7 ± 14.5 years, ranging from 2 - 82 years) were analysed. The mean 6-item score, determined according to Giangreco (J Pediatr 129:611-614, 1996), was 6.9 ± 2.5 points. At least one neurological finding each was noted in 53 patients (69.7 %). Specifically, ataxia was noted in 5 patients (6.6 %), lack of fine motor skills in 40 patients, (52.6 %), muscle tonus disorder in 4 patients (5.3 %), and other neurological disorders in 39 patients (51.3 %). Spasticity was not noted in any patient. Seizures were reported in 6 patients (8.1 %), anxiety disorders in 22 patients (30.1 %), depression in 7 patients (9.6 %), ADHD/ADD in 36 patients (49.3 %), impairment of social behavior in 39 patients (53.4 %), and other comorbidities in 23 patients (31.5 %). The mean Aberrant Behaviour Checklist Community Edition (ABC-C) score on behavioral symptoms, obtained in 71 patients at first documentation, was 48.4 ± 27.8 (median 45.0, range 5-115). The mean visual analogue scale (VAS) score, obtained in 59 patients at first documentation, was 84.9 ± 14.6 points (median 90; range 50 – 100). Conclusions This report describes the largest cohort of patients with FXS in Europe. The reported observations indicate a substantial burden of disease for patients and their caregivers. Based on these observations, an early expert psychiatric diagnosis is recommended for suspected FXS patients. Further recommendations include multimodal and multi-professional management that is tailored to the individual patient’s needs. Trial registration The ClinTrials.gov identifier is NCT01711606. Registered on 18 October 2012.

Importance Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high prevalence in adulthood. There is a recognized need to assess the efficacy of psychotherapy in adult ADHD. Objective To evaluate the efficacy of cognitive behavioral group psychotherapy (GPT) compared with individual clinical management (CM) and that of methylphenidate hydrochloride compared with placebo. Design, Setting, and Participants Prospective, multicenter, randomized clinical trial of 18- to 58-year-old outpatients with ADHD from 7 German study centers. Patients were recruited between January 2007 and August 2010, treatment was finalized in August 2011, and final follow-up assessments occurred in March 2013. Interventions Sessions of GPT and CM were held weekly for the first 12 weeks and monthly thereafter (9 months). Patients received either methylphenidate or placebo for 1 year. Main Outcomes and Measures The primary outcome was the change in the ADHD Index of the Conners Adult ADHD Rating Scale from baseline to the end of the 3-month intensive treatment (blinded observer ratings). Secondary outcomes included ADHD ratings after 1 year, blinded observer ratings using the Clinical Global Impression Scale, and self-ratings of depression. Results Among 1480 prescreened patients, 518 were assessed for eligibility, 433 were centrally randomized, and 419 were analyzed as randomized. After 3 months, the ADHD Index all-group baseline mean of 20.6 improved to adjusted means of 17.6 for GPT and 16.5 for CM, with no significant difference between groups. Methylphenidate (adjusted mean, 16.2) was superior to placebo (adjusted mean, 17.9) (difference, −1.7; 97.5% CI, −3.0 to −0.4; P = .003). After 1 year, treatment effects remained essentially stable. Descriptive analyses showed that methylphenidate was superior to placebo in patients assigned to GPT (difference, −1.7; 95% CI, −3.2 to −0.1; P = .04) or CM (difference, −1.7; 95% CI, −3.3 to −0.2; P = .03). Regarding depression, no significant differences were found. In contrast, GPT was superior to CM for all visits in the Clinical Global Impression global assessment of effectiveness. Conclusion and Relevance Highly structured group intervention did not outperform individual CM with regard to the primary outcome. Psychological interventions resulted in better outcomes during a 1-year period when combined with methylphenidate as compared with placebo. Trial Registration isrctn.org Identifier:ISRCTN54096201