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.

Current clinical practice of electroconvulsive therapy and repetitive transcranial magnetic stimulation in psychiatry, a German sample.

The purpose of the study was to evaluate the current clinical practice of Electroconvulsive Therapy and Repetitive Transcranial Magnetic Stimulation in German psychiatry. Case-based data (> 1.000.000 cases) were collected according to §21 of the German hospital remuneration law from January 2015 to December 2017. The study cohort comprises approximately 35-40% of the annual psychiatric cases and hospitals in Germany. Frequency of ECT and rTMS cases were investigated considering main diagnoses according to ICD-10 and treatment settings (inpatient vs. day-care). ECT cases with short-term hospitalization (≤ 4 days) were supposed to be maintenance ECT cases. A linear regression analysis was conducted to estimate trends in the use of ECT and rTMS. Different groups were compared using Chi-square tests. ECT and rTMS cases appear to increase in total during the observation period possibly due to facilities newly introducing ECT and rTMS but also to increased frequency of treatments. Both treatments were rarely performed in day-care settings (0.89% and 11.25%). ECT was performed in 1.72% of all cases with affective disorders and in 1.48% with major depressions, respectively. Age ≥ 65 years, females, severe and psychotic depression were significantly associated with a higher rate of ECT cases. > 40% of all ECT cases were possibly maintenance ECT cases. Only 0.60% of these were performed in day- care settings. rTMS was primarily performed in major depression (86,7% of all rTMS cases). This study suggests a growing demand for ECT and rTMS. Nevertheless, the use of ECT is still low compared to the high prevalence of treatment resistant depression. The use of rTMS is even lower and seems to be restricted to specialized institutions. Maintenance ECT is frequently carried out in an inpatient setting. Limitations of this study are the case- and group-based analysis, missing data on outpatient services and treatment sessions per case. Therefore, the database is not necessarily representative for the entire German healthcare system. Further studies are needed to verify the presented findings and should address the feasibility of ambulatory and day-care ECT services.

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.

Nuclear medical imaging as part of dementia diagnostics in psychiatric day-care clinics and inpatient care settings.

BACKGROUND: Current guidelines support the use of nuclear medical imaging (NMI) techniques for differential diagnostics of certain cases of dementia. AIMS: We aimed at studying the association between using NMI and the accuracy of dementia diagnoses. Additionally, we evaluated the effect of conducting NMI on the duration of hospital treatment. METHODS: This study was based on data collected according to §21 of the German hospital remuneration law, including relevant diagnostic and procedural codes for NMI in dementia patients. In total, more than 7.2 million cases treated in German psychiatric and somatic hospitals between 2015 and 2017 were included. Associations between the frequency of NMI and the accuracy of dementia diagnoses in terms of specific vs. unspecific diagnostic codes were analyzed using Fischer's exact test. RESULTS: In total, 351,106 cases with a dementia diagnosis were encoded during the study period. NMI was performed in 1.03% or 0.15% of all patients with dementia in psychiatric or somatic clinics, respectively. In psychiatric clinics, the proportion of unspecific dementia diagnoses decreased from 20.86% in 2015 to 17.73% in 2017. NMI was mainly performed within psychiatric day-care settings. Interestingly, patients receiving NMI stayed shorter within day-care settings (8.1 ± 16.0 days) compared to inpatient settings (38.3 ± 44.7 days). CONCLUSIONS: Nuclear medical imaging is often performed in psychiatric day-care settings. Further studies are warranted to understand the predictive diagnostic value of NMI in dementia diagnosis compared with clinical, CSF and structural imaging in different healthcare settings.

[Day care/inpatient psychiatric treatment of minors and adults with hyperkinetic disorder in German psychiatric hospitals : Basic conditions, diagnoses and comorbidities]. / (Teil-)stationäre Therapie von Voll- und Minderjährigen mit einer hyperkinetischen Störung in der deutschen Psychiatrie : Rahmenbedingungen, Diagnosevergabe und Komorbiditäten.

BACKGROUND: Hyperkinetic disorders (HKD, ICD-10 F90.­) have increasingly been the focus of research literature in recent years. Empirical studies analyzing the care situation in psychiatric clinics are so far primarily available for a few health insurances. This study analyzed a German sample from 2015 consisting of inpatient as well as day care psychiatric treatment cases from all statutory health insurances focusing on the care situation and differentiating between minor vs. adult patients with the main diagnosis HKD. MATERIAL AND METHODS: The study was based on the treatment relevant indicators in psychiatry and psychosomatics (VIPP) database, which contains data according to §21 of the Hospital Remuneration Act (KHEntgG). A total of 896 treatment cases with the diagnosis of HKD from the year 2015, based on anonymized routine records from 41 psychiatric clinics, were analyzed. RESULTS: The basic conditions for inpatient/day care psychiatric treatment significantly differed between minor vs. adult patients. Minors travelled greater distances to the treatment site, received more therapy units and stayed longer in the psychiatric clinic than adults. Significant differences were also found between the subgroups concerning the main diagnoses according to ICD-10 coding as well as comorbid mental disorders. CONCLUSION: Due to greater distances from their residence to a psychiatric hospital for minors, extension of capacities with a focus on child and youth psychiatry seems to be a reasonable conclusion. Simultaneously, the intensity of treatment seems to be lower for adult patients, despite a greatly increased number of secondary diagnoses and thus anticipated psychological stress. Transition difficulties from child and youth psychiatry to adult psychiatry may be a possible explanation for this discrepancy.

Association between longitudinal clinical outcomes in patients with hip fracture and their pre-fracture place of residence.

BACKGROUND: Clinical outcomes of patients with proximal femoral fracture within 1 year after hospitalization are presented. In particular, associations between the patients' clinical status and their pre-fracture residence were evaluated (community-dwelling vs nursing home). METHODS: Patients aged ≥60 years with proximal femoral fractures were included in a prospective, single-centre observational study and followed for 12 months. Patients' clinical status at baseline was compared to their health status at follow-up 12 months later. Several standardized questionnaires were used to evaluate the patients' functional and cognitive capacity (e.g. Lawton Instrumental Activities of Daily Living Scale, Barthel Index, and Mini-Mental State Examination), mobility (timed up-and-go test, Tinetti Test, and Harris Hip Score), quality of life (EuroQol-5 Dimensions index and EuroQol Visual Analogue Scale), and psychological status (Geriatric Depression Scale). RESULTS: This study included 402 patients (mean age: 81.3 ± 8.2 years, 72% women). Patients stayed in hospital for 13.7 ± 6.1 days on average. The comparison of patients' clinical status at baseline and at 12-month follow-up revealed that the Mini-Mental State Examination and Charlson Comorbidity Index remained unchanged (P = 0.527 and P = 0.705), the level of depression (Geriatric Depression Scale) significantly decreased (P < 0.001), and quality of life (EuroQol-5 Dimensions index) diminished (P < 0.001). Although patients' mobility increased after 12 months (P < 0.001 for timed up-and-go test and Harris Hip Score), their functional capacity was significantly reduced (P < 0.001 for Barthel Index and Lawton Instrumental Activities of Daily Living Scale). Nursing home residents showed a significantly higher impairment at baseline than community-dwelling individuals and less improvement in functional and cognitive tests at 12-month follow-up. CONCLUSIONS: Clinical outcomes after hip fracture are significantly associated with patients' pre-fracture residence status. Place of residence as well as functional and cognitive status on admission may lead to differences in functional recovery and affect therapeutic and rehabilitative decision-making.

Prescription of Benzodiazepines and Related Drugs in Patients with Mild Cognitive Deficits and Alzheimer's Disease.

INTRODUCTION: Benzodiazepines and related drugs (BZDR) should be avoided in patients with cognitive impairment. We evaluated the relationship between a BZDR treatment and the health status of patients with Alzheimer's disease (AD). METHODS: Cross-sectional study in 395 AD patients using bivariate and multiple logistic analyses to assess correlations between the prescription of BZDR and patients' characteristics (cognitive and functional capacity, health-related quality of life (HrQoL), neuropsychiatric symptoms). RESULTS: BZDR were used in 12.4% (n=49) of all participants. In bivariate analyses, the prescription was associated with a lower HrQoL, a higher need of care, and the presence of anxiety. Multivariate models revealed a higher risk of BZDR treatment in patients with depression (OR 3.85, 95% CI: 1.45 - 10.27). Community-dwelling participants and those treated by neurologists/psychiatrists had a lower risk of receiving BZDR (OR 0.33, 95% CI: 0.12 - 0.89 and OR 0.16, 95% CI: 0.07 - 0.36). DISCUSSION: The inappropriate use of BZDR conflicts with national and international guidelines. We suggest evaluating indications and treatment duration and improving the knowledge of alternative therapies in healthcare institutions.

Antidepressant medication in a German cohort of patients with Alzheimer's disease
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OBJECTIVE: The use of antidepressant drugs in dementia patients is associated with the risk of adverse events, and the evidence for relevant effects is scarce. We aimed to determine the associations between the prescription of antidepressants and patients' sociodemographic (e.g., age, gender, living situation) and clinical characteristics (e.g., disease severity, neuropsychiatric symptoms). MATERIALS AND METHODS: We included 395 institutionalized and community-dwelling patients with Alzheimer's disease (AD) across all severity stages of dementia in a cross-sectional study design. The patients' clinical characteristics comprised of cognitive status, daily activities, depressive symptoms, further neuropsychiatric symptoms, and health-related quality of life (HrQoL). We conducted multiple logistic regression analyses for the association between the use of antidepressant drugs and the covariates. RESULTS: Approximately 31% of the participants were treated with antidepressant drugs, with a higher chance of being medicated for institutionalized patients (χ2-test: p = 0.010). In the bivariate analyses, the use of antidepressants was significantly associated with higher levels of care, lower cognitive and daily life capacity, higher extent of neuropsychiatric symptoms, and a lower proxy-reported HrQoL. Finally, multiple logistic regression models showed a significantly higher use of antidepressants in patients treated by psychiatrists and neurologists (OR 2.852, 95% CI: 1.223 - 6.652). CONCLUSION: The use of antidepressant drugs in the study population was high, and the suitability of the treatment with antidepressants remains unclear. Participants with diminished cognitive and functional capacity, higher extent of neuropsychiatric symptoms, and those treated by neuropsychiatric specialists were more likely to be treated with antidepressants. The pharmaceutical treatment of patients with these clinical characteristics should be particularly considered in the daily care for dementia patients. Further longitudinal studies should evaluate the appropriateness of indications for antidepressants and the causative direction of correlations with the patients' clinical characteristics.
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Antipsychotic treatment of community-dwelling and institutionalised patients with dementia in Germany.

OBJECTIVE: A restrictive use of antipsychotic drugs in patients with Alzheimer's disease (AD) is recommended due to an increased risk of cerebrovascular events and mortality. We hypothesise that the prescription of antipsychotics is associated with the patients' socio-demographic and clinical status (e.g., dementia severity). METHODS: The prescription of antipsychotics was cross-sectionally evaluated in 272 community-dwelling and 123 institutionalised patients with AD across all severity stages of dementia. The patients' clinical characteristics covered the cognitive status, neuropsychiatric symptoms, daily activities, and quality of life (HrQoL). To determine associations with the use of antipsychotics bivariate and logistic regression analyses were conducted. RESULTS: Totally, 25% of the patients were treated with antipsychotics. significantly less frequently than nursing home inhabitants (15.1% vs. 45.5%). Severely demented patients (MMSE 0-9) received antipsychotics most often (51.5%). Additionally, multiple regression analyses revealed a higher chance of prescription for participants with depressive symptoms (OR 2.3, 95% CI: 1.019-5.160) and those treated by neuropsychiatric specialists (OR 3.4, 95% CI: 1.408-8.328). CONCLUSIONS: Further longitudinal studies are required to assess the appropriateness of indications for antipsychotics and the reasons for a higher use in nursing home inhabitants and patients with severe dementia and depression.

Cardiovascular and metabolic comorbidities in patients with Alzheimer's disease and vascular dementia compared to a psychiatric control cohort.

BACKGROUND: Multimorbidity in dementia is associated with an increased risk of complications and a higher need for care. Having knowledge of cardiovascular and metabolic comorbidities is crucial when making decisions about diagnostic procedures and therapies. We compared the prevalence of comorbidities in hospitalized patients with Alzheimer's disease (AD), vascular dementia, and psychiatric diseases other than dementia. Additionally, we compared clinically relevant health-care indicators (length of hospital stay, rate of re-hospitalization) between these groups. METHODS: We used information from a database of treatment-relevant indicators from psychiatric and psychosomatic hospitals throughout Germany. This database contains routinely recorded data collected from 85 German hospitals from 2011 to 2015. In total, 14 411 AD cases, 7156 vascular dementia cases, and 34 534 cases involving non-demented psychiatric patients (used as controls) were included. To analyze comorbidities and health-care indicators, χ2 tests and t-tests were used. RESULTS: Diabetes mellitus, lipoprotein disorders, coronary artery diseases, cardiac arrhythmia and insufficiency, and atherosclerosis were significantly more prevalent in patients with vascular dementia than in those with AD and psychiatric controls. Hypertension and coronary artery diseases were less frequently associated with AD than with non-demented psychiatric controls (P < 0.001). Additionally, dementia patients with cardiovascular or metabolic diseases exhibited longer hospital stays (+ 1.4 days, P < 0.001) and were more often re-hospitalized within 3 weeks (P < 0.001) and 1 year (P < 0.001) compared to dementia patients without these comorbidities. CONCLUSIONS: Awareness of somatic comorbidities in patients with dementia is crucial to avoid complications during inpatient treatment. The occurrence of comorbid disorders was associated with longer and more frequent hospital stays, which potentially lead to higher health-care costs. Further studies should evaluate the causative association between somatic comorbidities and inpatient costs in dementia patients.

[ADHD in Adults and Comorbid Substance Use Disorder: Prevalence, Clinical Diagnostics and Integrated Therapy]. / ADHS im Erwachsenenalter und substanzbezogene Störungen ­ Prävalenz, Diagnostik und integrierte Behandlungskonzepte.

Substance use disorders (SUD) are one of the most frequent mental disorders among adults. Attention-Deficit/Hyperactivity-Disorder (ADHD) is one of the most common mental health issues in childhood and adolescence, often persisting in adulthood. ADHD in childhood and adolescence is a robust predictor of tobacco, alcohol and illicit substance use in adulthood. Prevalence of comorbid ADHD in SUD patients is high. Nearly one quarter of these patients fulfill the DSM IV criteria for ADHD. Integrated concepts for treatment of SUD and ADHD are needed, but rare up to now. The aim of this review is to present and discuss recent scientific literature on the topic SUD and ADHD among adults and show its implications for clinical diagnostics and treatment.

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.

Evidence and expert consensus based German guidelines for the use of repetitive transcranial magnetic stimulation in depression.

INTRODUCTION: Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) offer a promising alternative to psychotherapeutic and pharmacological treatments for depression. This paper aims to present a practical guide for its clinical implementation based on evidence from the literature as well as on the experience of a group of leading German experts in the field. METHODS: The current evidence base for the use of rTMS in depression was examined via review of the literature. From the evidence and from clinical experience, recommendations for the use of rTMS in clinical practice were derived. All members of the of the German Society for Brain Stimulation in Psychiatry and all members of the sections Clinical Brain Stimulation and Experimental Brain Stimulation of the German Society for Psychiatry, Psychotherapy, Psychosomatics and Mental Health were invited to participate in a poll on whether they consent with the recommendations. FINDINGS: Among rTMS experts, a high consensus rate could be identified for clinical practice concerning the setting and the technical parameters of rTMS treatment in depression, indications and contra-indications, the relation of rTMS to other antidepressive treatment modalities and the frequency and management of side effects.

Claims Data Analysis on the Dispensing of Tricyclic Antidepressants Among Patients With Dementia in Germany.

Objective: A restrictive use of tricyclic antidepressants (TCA) in patients with dementia (PwD) is recommended due to the hazard of anticholinergic side effects. We evaluated the frequency of TCA dispensing in PwD over a period of 1 year and the use of TCA before and after the incident diagnosis of dementia. Methods: This analysis was based on administrative data from a German statutory health insurance for a period of 2 years. Totally, 20,357 patients with an incident diagnosis of dementia in 2014 were included. We evaluated the dispensing of TCA in 2015. Subgroup analyses were conducted to evaluate associations between the incident diagnosis of dementia and modifications in TCA dispensing. Results: In 2015, 1,125 dementia patients (5.5%) were treated with TCA and 31% were medicated with TCA in all four quarters of 2015. Most dispensings were conducted by general practitioners (67.9%). On average, patients received 3.7 ± 2.6 dispensings per year. Amitriptyline (56.3%), doxepin (26.8%), and trimipramine (16.8%) were dispensed most often. Subgroup analyses revealed that the dispensing of TCA remained mainly unchanged following the incident diagnosis. Conclusion: A relevant number of PwD were treated with TCA. To maintain the patients' safety, an improved implementation of guidelines for the pharmaceutical treatment of PwD in healthcare institutions might be required. Since 68% of the patients suffered from depression, future studies should further evaluate the indications for TCA.