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).

Mortality With and Without Whole-Body CT in Severely Injured Children.

BACKGROUND: The choice of imaging modality-the use of whole-body computed tomography (WB-CT) versus a step-wise diagnostic procedure-in injured children is controversial. In this study we availed ourselves of data from the TR-DGU, the trauma registry of the German Society for Trauma Surgery (Deutsche Gesellschaft für Unfallchirurgie), to investigate whether the use of WB-CT improves the outcome. METHODS: The TR-DGU data from the period 2012-2021 were evaluated. A three-stage analysis began with comparison of children with adults aged ≤ 50 years. As a second step, the observed and expected mortality in children with WB-CT was compared with the mortality in children without WB-CT. Finally, predictors of the use of WB-CT were identified so that a propensity score analysis of matched pairs could be performed. RESULTS: A total of 65 092 patients were included, 4573 children (7%) and 60 519 adults (93%), with differences in accident type and injury pattern. Comparison of the ratio of observed to expected mortality revealed no difference between the two groups of children (standardized mortality ratio 0.97 with WB-CT, 0.95 without WB-CT). In adults, however, there was an advantage for the WB-CT group. The propensity score analysis of 1101 matched pairs showed identical mortality in the two groups (3.9% with WB-CT, 4.0% without WB-CT). CONCLUSION: The TR-DGU data show no benefit of WB-CT compared with step-wise diagnosis in the care of severely injured children. In view of the radiation exposure involved, with the danger of inducing malignancy, the benefits and risks of the use of WB-CT in children should be weighed up carefully in team discussions.

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.

Preventing COVID-19 outbreaks through surveillance testing in healthcare facilities: a modelling study.

BACKGROUND: Surveillance testing within healthcare facilities provides an opportunity to prevent severe outbreaks of coronavirus disease 2019 (COVID-19). However, the quantitative impact of different available surveillance strategies and their potential to decrease the frequency of outbreaks are not well-understood. METHODS: We establish an individual-based model representative of a mental health hospital yielding generalizable results. Attributes and features of this facility were derived from a prototypical hospital, which provides psychiatric, psychosomatic and psychotherapeutic treatment. We estimate the relative reduction of outbreak probability for three test strategies (entry test, once-weekly test and twice-weekly test) relative to a symptom-based baseline strategy. Based on our findings, we propose determinants of successful surveillance measures. RESULTS: Entry Testing reduced the outbreak probability by 26%, additionally testing once or twice weekly reduced the outbreak probability by 49% or 67% respectively. We found that fast diagnostic test results and adequate compliance of the clinic population are mandatory for conducting effective surveillance. The robustness of these results towards uncertainties is demonstrated via comprehensive sensitivity analyses. CONCLUSIONS: We conclude that active testing in mental health hospitals and similar facilities considerably reduces the number of COVID-19 outbreaks compared to symptom-based surveillance only.

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.

Challenges in the Transition from In-Patient to Out-Patient Treatment in Depression.

BACKGROUND: Few data are available on the characteristics of inpatient treatment and subsequent outpatient treatment for depression in Germany. In this study, we aimed to characterize the inpatient and outpatient treatment phases, to determine the rates of readmission and mortality, and to identify risk factors. METHODS: We carried out a descriptive statistical analysis of routine administrative data from a large health-insurance carrier (BARMER). All insurees aged 18 to 65 who were treated in 2015 as inpatients on a psychiatry and psychotherapy service or on a psychosomatic medicine and psychotherapy service with a main diagnosis of depression were included in the analysis. Risk factors for readmission and death were determined with the aid of mixed logistic regression. RESULTS: Of the 22 893 patients whose data were analyzed, 78% had been hospitalized on a psychiatry and psychotherapy service and 22% on a psychosomatic medicine and psychotherapy service. The median length of hospital stay was 42 days. Follow-up care in the outpatient setting failed to conform with the recommendations of the pertinent guidelines in 92% of the patients with a main diagnosis of severe depression during hospitalization, and in 50% of those with moderate depression. 21% of the patients were readmitted within a year. The mortality at one year was 961 per 100 000 individuals (adjusted for the age and sex structure of the German population), or 3.4 times the mortality of the population at large. In the regression model, more treatment units during hospitalization and subsequent treatment with psychotherapy were associated with a lower probability of readmission, while longer hospitalization with subsequent pharmacotherapy or psychotherapy was associated with lower mortality. CONCLUSION: The recommendations of the national (German) S3 guidelines for the further care of patients who have been hospitalized for depression are inadequately implemented at present in the sectored structures of in- and outpatient care in the German health care system. This patient group has marked excess mortality.

Psychological interventions for posttraumatic stress disorder involving primary care physicians: systematic review and Meta-analysis of randomized controlled trials.

BACKGROUND: Evidence-based psychological interventions for posttraumatic stress disorder (PTSD) are available in specialized settings, but adequate care in primary care is often lacking. The aim of this systematic review was to determine the effectiveness of psychological interventions for PTSD involving primary care physicians (PCPs) and to characterize these interventions as well as their providers. METHOD: A systematic review and meta-analyses of randomized controlled trials (RCTs). Primary outcome were symptoms of PTSD. RESULTS: Four RCTs with a total of 774 patients suffering from PTSD symptoms were included, all applying cognitive behavioural based interventions. Three studies with psychological interventions being conducted by case managers were pooled in a meta-analysis. Interventions were not effective in the short term (0-6 months; SMD, - 0.1; 95% CI, - 0.24-0.04; I2 = 0%). Only two studies contributed to the meta-analysis for long term (12-18 months) outcomes yielding a small effect (SMD, - 0.23; 95% CI, - 0.38- -0.08; I2 = 0%). CONCLUSIONS: Psychological interventions for PTSD in primary care settings may be effective in the long term but number and quality of included studies was limited so the results should be interpreted with caution.

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.

Two-Year Follow-Up after Treatment with the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for Early-Onset Chronic Depression.

BACKGROUND: Evidence on the long-term efficacy of psychotherapeutic approaches for chronic depression is scarce. OBJECTIVE: To evaluate the effects of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared to Supportive Psychotherapy (SP) 1 year and 2 years after treatment termination. METHODS: In this study, we present 1- and 2-year follow-up assessments of a prospective, multicenter, evaluator-blinded, randomized clinical trial of outpatients with early-onset chronic major depression (n = 268). The initial treatment included 32 sessions of CBASP or SP over 48 weeks. The primary outcome was the rate of "well weeks" (Longitudinal Interval Follow-Up Evaluation; no/minimal symptoms) after 1 year and 2 years. The secondary outcomes were, among others, clinician- and self-rated depressive symptoms, response/remission rates, and quality of life. RESULTS: Of the 268 randomized patients, 207 (77%) participated in the follow-up. In the intention-to-treat analysis, there was no statistically significant difference between CBASP and SP patients in experiencing well weeks (CBASP: mean [SD] of 48.6 [36.9] weeks; SP: 39.0 [34.8]; rate ratio 1.26, 95% CI 0.99-1.59, p = 0.057, d = 0.18) and in remission rates (CBASP: 1 year 40%, 2 years 40.2%; SP: 1 year 28.9%, 2 years 33%) in the 2 years after treatment. Statistically significant effects were found in favor of CBASP 1 year after treatment termination regarding the rate of well weeks, self-rated depressive symptoms, and depression-related quality of life. CONCLUSIONS: CBASP lost its superiority over SP at some point between the first and the second year. This suggests the necessity of maintenance treatment for early-onset chronically depressed patients remitted with CBASP during the acute therapy phase, as well as the sequential integration of other treatment strategies, including medication for those who did not reach remission.

Long-term outcome of a mental health promotion program in Germany.

Mental health promotion programs (MHP) seek to reduce sub-syndromal symptoms of mental distress and enhance positive mental health. This study evaluates the long-term effects of a mindfulness-based MHP program ('Life Balance') provided by health coaches in a multi-site field setting on mental distress, satisfaction with life and resilience. Using a controlled design, propensity score matching was used to select a control group for participants of the MHP. The total study sample (N = 3624) comprised 83% women, with a mean age of 50 years. Data was collected via mailings 1 year after study entry. Results suggest participants experience reduced emotional distress at 12-month follow-up, with a medium between-group effect size (d = 0.40) for those participants who showed clinically relevant symptoms of mental distress at study entry. The effects of the program were more pronounced in participants with higher initial distress scores. New cases of psychopathological symptoms were prevented in 1 of 16 participants. Satisfaction with life and resilience were enhanced significantly. Our data suggest 'Life Balance' shows long-term effectiveness and indicate it is possible to design MHP programs that serve as both primary and indicated prevention, and that these programs can be applied on a population basis.

[Attendance for Using Internet-Based Support After Inpatient Treatment - A Cross-Sectional Survey]. / Bereitschaft zur Inanspruchnahme internetbasierter Unterstützung nach stationärer Behandlung ­ eine Querschnittstudie.

OBJECTIVE: Examination of the attendance for using internet-based measures after inpatient treatment. METHODS: Cross-sectional-survey in former inpatients (N = 247). RESULTS: 44.9 % are willing to use measures via videoconference, 34.7 % via Chat, 50.0 % via E-Mail and 38.0 % as onlinetherapy. Attendance is lower in older age groups. Benefits regarding the introduced measures are seen mainly in the flexibility and disadvantages in the impersonal character. CONCLUSIONS: A relevant share of especially younger patients is willing to use internet-based measures.

Work-Time Distribution of Physicians at a German University Hospital.

BACKGROUND: The effective utilization of staff resources is of decisive importance for the adequate, appropriate, and economical delivery of hospital services. The goal of this study was to determine the distribution of working time among doctors in a German university hospital-in particular, in terms of type of activities and time of day. METHODS: The distribution of working time was determined from 14-day samples taken in seven clinical departments of the Medical Center-University of Freiburg. In each 14-day sample, the activities being carried out at multiple, randomly chosen times were recorded. RESULTS: A total of 250 doctors (participation rate: 83%) took part in the study. A total of 20 715 hours of working time was analyzed, representing twelve years of full-time employment. Overall, 46% of working time in the inpatient sector was spent in direct contact with patients, with relevant differences among the participating clinical departments: for instance, the percentage of time taken up by patient contact was 35% in pediatrics and 60% in oral and maxillofacial surgery. Patient contact was highest (over 50% overall) in the period 8 a.m. to 12 noon. CONCLUSION: The amount of working time taken up by activities other than direct patient contact was found to be lower than in previous studies. It remains unclear what distribution of working time is best for patient care and whether it would be possible or desirable to increase the time that doctors spend in direct contact with patients.

The impact of childhood maltreatment on the differential efficacy of CBASP versus escitalopram in patients with chronic depression: A secondary analysis.

Childhood maltreatment (CM) has been indicated as a predictor of a differential response to antidepressant treatment with psychotherapy compared to medication. In this secondary analysis, we investigated whether the presence of CM results in a differential indication for the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) or escitalopram plus clinical management (ESC). Sixty patients with chronic depression were randomized to either 22 sessions of CBASP or ESC over the course of 8 weeks of acute and 20 weeks of extended treatment at 2 German treatment sites. CM was assessed using the Childhood Trauma Questionnaire and the clinician rated Early Trauma Inventory. Intention-to-treat analyses were used to examine the impact of CM on depression, global functioning, and quality of life. The presence of CM did not result in significant differences in treatment response to CBASP or ESC on any outcome measure after 28 weeks of treatment independent of the type of CM assessment. After 8 weeks, a significant CM × treatment interaction was found for scores on the Montgomery-Asberg Depression Rating Scale. Patients with a history of CM receiving CBASP had a significantly lower response rate compared to patients without CM and to those receiving ESC after 8 weeks. Conclusively, CBASP and ESC are equally effective treatment options for the difficult to treat subgroup of patients with chronic depression and a history of CM. CM may be a predictor of a longer latency of treatment response in the case of psychotherapy. KEY PRACTITIONER MESSAGE: CBASP and escitalopram are equally effective treatment options for chronic depression. Both treatments are also equally effective for the difficult to treat subgroup of patients with chronic depression and a history of childhood maltreatment. Childhood maltreatment may result in a longer latency of treatment response in the case of psychotherapy.

Effect of Disorder-Specific vs Nonspecific Psychotherapy for Chronic Depression: A Randomized Clinical Trial.

IMPORTANCE: Chronic depression is a highly prevalent and disabling disorder. There is a recognized need to assess the value of long-term disorder-specific psychotherapy. OBJECTIVE: To evaluate the efficacy of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared with that of nonspecific supportive psychotherapy (SP). DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter, evaluator-blinded, randomized clinical trial was conducted among adult outpatients with early-onset chronic depression who were not taking antidepressant medication. Patients were recruited between March 5, 2010, and October 16, 2012; the last patient finished treatment on October 14, 2013. Data analysis was conducted from March 5, 2014, to October 27, 2016. INTERVENTIONS: The treatment included 24 sessions of CBASP or SP for 20 weeks in the acute phase, followed by 8 continuation sessions during the next 28 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was symptom severity after 20 weeks (blinded observer ratings) as assessed by the 24-item Hamilton Rating Scale for Depression (HRSD-24). Secondary outcomes were rates of response (reduction in HRSD-24 score of ≥50% from baseline) and remission (HRSD-24 score ≤8), as well as self-assessed ratings of depression, global functioning, and quality of life. RESULTS: Among 622 patients assessed for eligibility, 268 were randomized: 137 to CBASP (96 women [70.1%] and 41 men [29.9%]; mean [SD] age, 44.7 [12.1] years) and 131 to SP (81 women [61.8%] and 50 men [38.2%]; mean [SD] age, 45.2 [11.6] years). The mean (SD) baseline HRSD-24 scores of 27.15 (5.49) in the CBASP group and 27.05 (5.74) in the SP group improved to 17.19 (10.01) and 20.39 (9.65), respectively, after 20 weeks, with a significant adjusted mean difference of -2.51 (95% CI, -4.16 to -0.86; P = .003) and a Cohen d of 0.31 in favor of CBASP. After 48 weeks, the HRSD-24 mean (SD) scores were 14.00 (9.72) for CBASP and 16.49 (9.96) for SP, with an adjusted difference of -3.13 (95% CI, -5.01 to -1.25; P = .001) and a Cohen d of 0.39. Patients undergoing CBASP were more likely to reach response (48 of 124 [38.7%] vs 27 of 111 [24.3%]; adjusted odds ratio, 2.02; 95% CI, 1.09 to 3.73; P = .03) or remission (27 of 124 [21.8%] vs 14 of 111 [12.6%]; adjusted odds ratio, 3.55; 95% CI, 1.61 to 7.85; P = .002) after 20 weeks. Patients undergoing CBASP showed significant advantages in most other secondary outcomes. CONCLUSIONS AND RELEVANCE: Highly structured specific psychotherapy was moderately more effective than nonspecific therapy in outpatients with early-onset chronic depression who were not taking antidepressant medication. Adding an extended phase to acute psychotherapy seems promising in this population. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00970437.

The effect of methylphenidate intake on brain structure in adults with ADHD in a placebo-controlled randomized trial.

BACKGROUND: Based on animal research several authors have warned that the application of methylphenidate, the first-line drug for the treatment of attention-deficit/hyperactivity disorder (ADHD), might have neurotoxic effects potentially harming the brain. We investigated whether methylphenidate application, over a 1-year period, results in cerebral volume decrease. METHODS: We acquired structural MRIs in a double-blind study comparing methylphenidate to placebo. Global and regional brain volumes were analyzed at baseline, after 3 months and after 12 months using diffeomorphic anatomic registration through exponentiated lie algebra. RESULTS: We included 131 adult patients with ADHD into the baseline sample, 98 into the 3-month sample (54 in the methylphenidate cohort and 44 in the placebo cohort) and 76 into the 1-year sample (37 in the methylphenidate cohort and 29 in the placebo cohort). Methylphenidate intake compared with placebo did not lead to any detectable cerebral volume loss; there was a trend toward bilateral cerebellar grey matter increase. LIMITATIONS: Detecting possible neurotoxic effects of methylphenidate might require a longer observation period. CONCLUSION: There is no evidence of grey matter volume loss after 1 year of methylphenidate treatment in adult patients with ADHD.

Correction: Polysomnographic Characteristics of Sleep in Stroke: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.1371/journal.pone.0148496.].

Polysomnographic Characteristics of Sleep in Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Research on sleep after stroke has focused mainly on sleep disordered breathing. However, the extend to which sleep physiology is altered in stroke survivors, how these alterations compare to healthy volunteers, and how sleep changes might affect recovery as well as physical and mental health has yet to be fully researched. Motivated by the view that a deeper understanding of sleep in stroke is needed to account for its role in health and well-being as well as its relevance for recovery and rehabilitation, we conducted a systematic review and meta-analysis of polysomnographic studies comparing stroke to control populations. METHOD: Medline and PsycInfo databases were searched using "stroke" and words capturing polysomnographic parameters as search terms. This yielded 1692 abstracts for screening, with 15 meeting the criteria for systematic review and 9 for meta-analysis. Prisma best practice guidelines were followed for the systematic review; the Comprehensive Meta-Analysis software was used for random effects modelling. RESULTS: The meta-analysis revealed that patients with stroke have poorer sleep than controls. Patients had lower sleep efficiency (mean 75% vs 84%), shorter total-sleep-time (309.4 vs 340.3 min) and more wake-after-sleep-onset (97.2 vs 53.8 min). Patients also spend more time in stage 1 (13% vs 10%) and less time in stage 2 sleep (36% vs 45%) and slow-wave-sleep (10% vs 12%). No group differences were identified for REM sleep. The systematic review revealed a strong bias towards studies in the early recovery phase of stroke, with no study reporting specifically on patients in the chronic state. Moreover, participants in the control groups included community samples as well as other patients groups. CONCLUSIONS: These results indicate poorer sleep in patients with stroke than controls. While strongly suggestive in nature, the evidence base is limited and methodologically diverse, and hands a clear mandate for further research. A particular need regards polysomnographic studies in chronic community-dwelling patients compared to age-matched individuals.