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

Abstract 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 wh…

Depression and Movement Disorders

Long-term improvement of quality of life in adult ADHD – results of the randomized multimodal COMPAS trial

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 treatme…

Neural correlates of intimate picture stimuli in females

Jacob et al. (2011) previously reported on intimate picture stimuli for emotion research in females in Psychiatry Research. Difficulties to engage in intimate relations constitute problems of many mental disorders, and intimacy must be differentiated from pure sex drive. Functional neuroimaging is an important tool to understand the pathophysiology of psychiatric disorders. We now studied cerebral activation in response to intimate stimuli in 35 healthy women. Comparison stimuli were taken from the International Affective Picture System. Neuroimaging revealed increased activation in bilateral occipitotemporal, parietal and anterior cingulate cortices extending to the orbitofrontal area. The…

Fear Network Unresponsiveness in Women with Anorexia Nervosa

Neurochemical alterations in women with borderline personality disorder and comorbid attention-deficit hyperactivity disorder

Borderline personality disorder (BPD) is associated with structural and functional brain changes. Recent models and findings refer to alterations of glutamate and total N-acetylaspartate (tNAA) in this condition.Absolute quantities of tNAA, creatine, glutamate, glutamine, myoinositol and total choline were measured using 3 Tesla magnetic resonance spectroscopy of the left anterior cingulate cortex and the left cerebellum in 14 unmedicated women with BPD and comorbid attention-deficit hyperactivity disorder (ADHD) and 18 healthy women. Both groups were matched with respect to age, education and premorbid intelligence.In the anterior cingulate, we found significantly higher tNAA and glutamate…

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

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 wit…

Neural correlates of interference inhibition, action withholding and action cancelation in adult ADHD

Attention-Deficit/Hyperactivity Disorder (ADHD) is marked by inhibitory and attentional deficits which can persist into adulthood. Those deficits have been associated with dysfunctional fronto-striatal and fronto-parietal circuits. The present study sought to delineate neural correlates of component specific inhibitory deficits in adult ADHD using functional magnetic resonance imaging (fMRI). 20 adult ADHD patients and 24 matched healthy controls were included. Brain activation was assessed during three stages of behavioral inhibition, i.e. interference inhibition (Simon task), action withholding (Go/no-go task) and action cancelation (Stop-signal task). Behaviorally, ADHD patients were aff…

Effectiveness of Psychotherapy in Adult ADHD: What Do Patients Think? Results of the COMPAS Study

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 manage…

Extraction of prefronto-amygdalar pathways by combining probability maps

Many recent studies reported altered functional connectivity within the frontolimbic circuitry in a wide range of neuropsychiatric disorders. However, functional connectivity must rely on structural connections. In this study we applied a novel probabilistic fiber tracking method to assess the structural connectivity between the amygdala and different prefrontal brain regions in vivo. Twenty healthy subjects were investigated with diffusion tensor imaging. Probabilistic fiber tracking was started from the amygdala and different prefrontal brain regions. Resulting probability maps were combined using an extended multiplication of probabilistic maps to identify the most probable anatomical pa…

Interindividual synchronization of brain activity during live verbal communication

Verbal social interaction plays an important role both in the etiology and treatment of psychiatric disorders. However, the neural basis of social interaction has primarily been studied in the individual brain, neglecting the inter-individual perspective. Here, we show inter-individual neuronal coupling of brain activity during live verbal interaction, by investigating 11 pairs of good female friends who were instructed to speak about autobiographical life events during simultaneous fMRI acquisition. The analysis revealed that the time course of neural activity in areas associated with speech production was coupled with the time course of neural activity in the interlocutor's auditory corte…

Recovery of cortical volume and thickness after remission from acute anorexia nervosa

Objective Reduced grey (GM) and white matter (WM) volumes and increased cerebrospinal fluid (CSF) have been frequently reported in anorexia nervosa (AN), but studies focusing on cortical thickness (CT) are scarce and findings inconsistent. We conducted the first study in AN that analyzed both parameters in the same study to gain novel and comprehensive insight. Method Voxel-based morphometry (VBM) analysis was performed on T1-weighted magnetic resonance images from 34 predominantly adult women with acute AN, 24 REC participants, and 41 healthy controls (HC). Global brain segment volumes (GM, WM, and CSF), regional GM volume, and cortical thickness measures were obtained from the same study …

Reduced interhemispheric structural connectivity between anterior cingulate cortices in borderline personality disorder

Functional and structural alterations of the anterior cingulate cortex (ACC), a key region for emotional and cognitive processing, are associated with borderline personality disorder (BPD). However, the interhemispheric structural connectivity between the left and right ACC and between other prefrontal regions in this condition is unknown. We acquired diffusion-tensor imaging data from 20 healthy women and 19 women with BPD and comorbid attention-deficit hyperactivity disorder (ADHD). Interhemispheric structural connectivity between both sides of the ACC, dorsolateral prefrontal cortices and medial orbitofrontal cortices was assessed by a novel probabilistic diffusion tensor-based fiber tra…

Frontocingular Dysfunction in Bulimia Nervosa when Confronted with Disease-specific Stimuli

Objective Bulimia nervosa (BN) is characterized by dysregulation of impulse control, in other words, uncontrolled eating. Functional neuroimaging studies have been sparse and have used variable methodologies. Method Thirteen medication-free female BN patients and 13 female healthy controls were investigated by functional magnetic resonance imaging using a disease-specific food paradigm. Stimuli were rated after the scanning procedure. Results Bulimia nervosa patients showed increased fear ratings and a trend for increased disgust. Magnetic resonance imaging data of 10 BN patients could be analysed. Three BN patients had to be excluded from the analysis because of minimal blood oxygen level …

Effects of Group Psychotherapy, Individual Counseling, Methylphenidate, and Placebo in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder

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 assessmen…

Neurobiological signature of intimacy in anorexia nervosa

Background Intimacy and psychosexual development represent core problems of anorexia nervosa (AN). Experiential and neurobiological evidence however is scarce. Material and methods Thirty-one female AN patients were compared with 35 non-patients (NP) and 22 recovered participants (REC) by using functional magnetic resonance imaging. Participants viewed pictures of couples in intimate relationships and control stimuli. Results AN patients experienced intimate stimuli with lower valence and dominance. AN showed decreased activation of parietal cortices. NP decreased the prefrontal cortex response, which AN patients did not. REC participants did not differ from NP on a behavioural level, thoug…