The impact of aerobic endurance training on cognitive performance in schizophrenic inpatients in a clinical routine setting.

The primary aim of this study was to investigate the impact of aerobic endurance training in schizophrenic inpatients on cognitive performance in a clinical routine setting. Of secondary interest was the influence on psychopathological symptoms. A total of 31 schizophrenic inpatients were randomly assigned to receive either controlled endurance training or occupational therapy. The experimental group underwent endurance training of 20-30 min each, 3 times per week for a total of up to 22 training sessions. The control group received about 90 min of occupational therapy, 2-3 times per week for up to 22 sessions. Cognitive performance was assessed via an extensive neuropsychological examination before randomization and prior to discharge. Significant improvements in cognitive functions and psychopathology could be shown in both groups. For verbal memory functions (short-term memory, working memory, and learning performance), there was a significant advantage for the aerobic endurance training group. Physical exercise is a feasible, easy-to-implement add-on therapy for schizophrenic patients in a clinical routine setting with positive effects on verbal memory functions. Besides, it seems important to fill the gap between inpatient and outpatient health care, providing physical training supply for this patient group.

The Effect of Nabiximols on Driving Ability in Adults with Chronic Tic Disorders: Results of a Substudy Analysis of the Double-Blind, Randomized, Placebo-Controlled CANNA-TICS Trial.

Background: The multicenter, randomized, double-blind, parallel-group, phase IIIb CANNA-TICS (CANNAbinoids in the treatment of TICS) trial showed clear trends for improvement of tics, depression, and quality of life with nabiximols versus placebo in adult patients with Gilles de la Tourette syndrome and other chronic tic disorders. Although in general nabiximols was well tolerated, it is unclear whether treatment using this cannabis extract influences driving skills in patients with chronic tic disorders. Methods: Here we report results of the "Fitness to Drive" substudy of the CANNA-TICS trial. The key endpoint was fitness to drive as a binary criterion with a computerized assessment at baseline and after 9 weeks of stable treatment (week 13) with nabiximols or placebo. A patient was considered unfit to drive according to the German Federal Highway Research Institute guidelines. Results: In the substudy, a total of 64 patients (76.6% men, mean±standard deviation of age: 36.8±13.9) were recruited at two study sites. The number of patients who were fit to drive increased from 24 (55.8%) at baseline to 28 (71.8%) at week 13 among 43 patients treated with nabiximols, and decreased from 14 (66.7%) to 10 (52.6%) among 21 patients who received placebo. The risk difference (nabiximols - placebo) was 0.17 (95% confidence interval=-0.08 to 0.43) in favor of nabiximols. Specifically, only 2 of 24 (8.3%) patients in the nabiximols, but 4 of 14 (28.6%) patients in the placebo group changed for the worse from fit (at baseline) to unfit (at week 13) to drive, whereas 8 of 19 (42.1%) patients in the nabiximols, and only 2 of 7 (28.6%) patients in the placebo group improved from unfit to fit. Conclusion: Treatment with nabiximols does not impair skills relevant to driving in those patients with tic disorders who were fit to drive at baseline and even improved fitness to drive in a subset of patients who were unfit to drive before start of treatment. EudraCT number: 2016-000564-42.

Driving-related cognitive skills during antidepressant transcranial direct current stimulation: results in a subsample from the DepressionDC trial.

Therapeutic transcranial direct current stimulation (tDCS) is a well-tolerated neuromodulatory intervention. However, there are currently no data on its impact on driving skills. Therefore, we conducted a validated assessment of driving-related cognitive skills in participants of the DepressionDC trial, a multicenter, randomized-controlled trial investigating the antidepressant effects of 6-week prefrontal tDCS in patients with major depressive disorder (MDD). Twenty-one patients (12 women, active tDCS, n = 11, sham, n = 10) underwent an assessment of driving-related cognitive skills before and after the intervention. Using a Bayesian analysis approach, we found no group differences between active tDCS and sham tDCS in the pre-post treatment changes for visual perception (estimated median difference: 3.41 [-3.17, 10.55 89%-CI], BF01: 2.1), stress tolerance (estimated median difference: 0.77 [-2.40, 4.15 89%-CI], BF01: 1.6), and reaction time (estimated median difference: 2.06 [-12.33, 16.83 89%-CI], BF01: 6.5). Our results indicate that repeated sessions of a conventional bifrontal tDCS protocol do not negatively impact driving-related cognitive skills in patients with MDD.

Protocol for the conceptualization and evaluation of a screening-tool for fitness-to-drive assessment in older people with cognitive impairment.

INTRODUCTION: Due to aging and health status people may be subjected to a decrease of cognitive ability and subsequently also a decline of driving safety. On the other hand there is a lack of valid and economically applicable instruments to assess driving performance. OBJECTIVE: The study is designed to develop a valid screening-tool for fitness-to-drive assessment in older people with cognitive impairment externally validated on the basis of on-road driving performance. METHODS: In a single-centre, non-randomized cross-sectional trial cognitive functioning and on-road-driving-behavior of older drivers will be assessed. Forty participants with cognitive impairment of different etiology and 40 healthy controls will undergo an extensive neuropsychological assessment. Additionally, an on-road driving assessment for external validation of fitness to drive will be carried out. Primary outcome measures will be performance in attention, executive functions and visuospatial tasks that will be validated with respect to performance on the on-road-driving-test. Secondary outcome measures will be sociodemographic, clinical- and driving characteristics to systematically examine their influence on the prediction of driving behavior. DISCUSSION: In clinical practice counselling patients with respect to driving safety is of great relevance. Thus, having valid, reliable, time economical and easily interpretable screening-tools on hand to counsel patients is of great relevance for practitioners. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee at the Ludwig-Maximilians-University Munich. The trial results will be disseminated through peer-reviewed publications and various conferences. TRIAL REGISTRATION: 18-640. Trial registration: German Clinical Trials Register. Registration number: DRKS00023549.

Driving Performance Under Treatment of Most Frequently Prescribed Drugs for Mental Disorders: A Systematic Review of Patient Studies.

BACKGROUND: Mobility is important for daily life functioning, with particular challenges regarding road safety under pharmacological treatment in patients with a psychiatric disease. METHODS: According to PRISMA guidelines, a systematic literature search on PubMed database (January 1970 to December 2020) was performed. Primary endpoints were driving performance in on-road tests, driving simulator performance, or psychomotor and visual perception functions assessed to estimate fitness to drive according to legal regulations in patient studies. RESULTS: Forty studies were identified (1533 patients, 38% female, median age 45 years), of which more than 60% were cross-sectional and open-label trials. Under steady-state medication, 31% (range 27%-42.5%) of schizophrenic or schizoaffective patients under antipsychotics and 18% (range 16%-20%) of unipolar and bipolar patients under antidepressants showed severe impairment in skills relevant for driving. Data point to an advantage of second-generation antipsychotics compared with first-generation antipsychotics as well as modern antidepressants over tricyclic antidepressants with respect to driving. Most patients significantly improved or stabilized in driving skills within 2-4 weeks of treatment with non-sedative or sedative antidepressants. Diazepam significantly worsened driving the first 3 weeks after treatment initiation, whereas medazepam (low dose), temazepam, and zolpidem did not impair driving. In long-term users of sedating antidepressants or benzodiazepines, impairments in on-road tests were not evident. CONCLUSION: The available evidence suggests that psychopharmacologic medicines improve or at least stabilize driving performance of patients under long-term treatment when given on clinical considerations. To enhance treatment compliance, existing classification systems of medicinal drugs concerning impact on driving performance should also incorporate information about effects of long-term-treatment.

The CANNA-TICS Study Protocol: A Randomized Multi-Center Double-Blind Placebo Controlled Trial to Demonstrate the Efficacy and Safety of Nabiximols in the Treatment of Adults With Chronic Tic Disorders.

Background: Gilles de la Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by motor and vocal tics. First-line treatments for tics are antipsychotics and tic-specific behavioral therapies. However, due to a lack of trained therapists and adverse events of antipsychotic medication many patients seek alternative treatment options including cannabis. Based on the favorable results obtained from case studies on different cannabis-based medicines as well as two small randomized controlled trials using delta-9-tetrahydrocannabinol (THC), we hypothesize that the cannabis extract nabiximols can be regarded as a promising new and safe treatment strategy in TS. Objective: To test in a double blind randomized clinical trial, whether treatment with the cannabis extract nabiximols is superior to placebo in patients with chronic tic disorders. Patients and Methods: This is a multicenter, randomized, double-blind, placebo controlled, parallel-group, phase IIIb trial, which aims to enroll 96 adult patients with chronic tic disorders (TS or chronic motor tic disorder) across 6 centers throughout Germany. Patients will be randomized with a 2:1 ratio into a nabiximols and a placebo arm. The primary efficacy endpoint is defined as tic reduction of at least 30% (compared to baseline) according to the Total Tic Score of the Yale Global Tic Severity Scale (YGTSS-TTS) after 13 weeks of treatment. In addition, several secondary endpoints will be assessed including changes in different psychiatric comorbidities, quality of life, driving ability, and safety assessments. Discussion: This will be the first large, controlled study investigating efficacy and safety of a cannabis-based medicine in patients with TS. Based on available data using different cannabis-based medicines, we expect not only a reduction of tics, but also an improvement of psychiatric comorbidities. If the cannabis extract nabiximols is proven to be safe and effective, it will be a valuable alternative treatment option. The results of this study will be of high health-economic relevance, because a substantial number of patients uses cannabis (illegally) as self-medication. Conclusion: The CANNA-TICS trial will clarify whether nabiximols is efficacious and safe in the treatment of patients with chronic tic disorders. Clinical Trial Registration: This trial is registered at clinicaltrialsregister.eu (Eudra-CT 2016-000564-42) and clinicaltrials.gov (NCT03087201).

[Evaluation of a neuropsychological test battery with psychiatric and psychosomatic patients]. / Evaluation einer neuropsychologischen Testbatterie an psychiatrischen und psychosomatischen Patienten.

Neuropsychological assessment should be an integral component of clinical psychiatric diagnostics. Yet, the commonly used tests have not been investigated adequately for this population so far. The current study evaluated a clinically approved neuropsychological test battery by analyzing data on 226 mentally ill patients using factor and regression analyses. The extraction of three factors (Speed, Memory, and Executive Functions) proved to be adequate as the tests could be allocated properly. Regression analysis revealed an economical basis assessment consisting of three tests (TAP Alertness, VLMT, and Matrices Test). Based on acceptance, economy, and factorial structure aspects, we recommend the investigated test battery for neuropsychological assessment of psychiatric and psychosomatic patients.

The Effects of Transcranial Direct Current Stimulation (tDCS) on Psychomotor and Visual Perception Functions Related to Driving Skills.

Objective: It could be demonstrated that anodal transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex (DLPFC) enhances accuracy in working memory tasks and reaction time in healthy adults and thus may also have an influence on complex everyday tasks like driving a car. However, no studies have applied tDCS to psychomotor skills related to a standard driving test so far. Methods: 10 female and 5 male healthy adults without any medication and history of psychiatric or neurological illness were randomly assigned to two groups receiving active and sham stimulation in a double blind, cross-over study design. Standardized computerized psychomotor tests according to the German guidelines for road and traffic safety were administered at baseline. Then they performed the same tests during an anodal or sham tDCS of the left DLPFC in two separated sessions. Results: No significant improvements in skills related to driving performance like visual perception, stress tolerance, concentration, and vigilance could be shown after left anodal prefrontal tDCS. Side effects were low and did not differ between active and sham stimulation. Conclusions: The findings of our study indicate that left prefrontal tDCS may not alter driving skills affording more automated action patterns but as shown in previous studies may have an influence on driving behavior requiring executive control processes. This however has to be proved in future studies and within greater samples.

Driving Under the Influence of Antidepressants: A Systematic Review and Update of the Evidence of Experimental and Controlled Clinical Studies.

Introduction This review provides an update of experimental and clinical studies on the effects of antidepressants on driving performance. Methods A systematic literature search on the PubMed database (1980-2016) was performed. Results Twenty-eight studies could be included in this review, whereas only 5 studies investigated driving performance under antidepressants in patients. Most tri- and tetracyclics have acute deleterious effects on driving performance that, except for mianserin, attenuate after subchronic use. Selective serotonin reuptake inhibitors and the serotonin norepinephrine reuptake inhibitor's venlafaxine and milnacipran did not affect driving ability. Trazodone appears to have dose-related acute effects on driving skills. Acute use of mirtazapine does produce impairments that diminish when given as a nocturnal dose and cannot be seen in healthy subjects when initially given as a low dose or after repeated dosing. Additive effects with alcohol were most pronounced with sedating antidepressants. Most patients definitely benefit from treatment with newer antidepressants with respect to driving skills. Discussion Much more patient studies are needed to elucidate a crucial question: from which antidepressant treatment do patients benefit most with respect to driving performance?

Driving skills in unmedicated first- and recurrent-episode schizophrenic patients.

The present study was designed to examine driving skills according to regulations of the German guidelines for road and traffic safety in unmedicated schizophrenic inpatients. A total of 13 first-episode (FES) and 13 recurrent-episode (RES) schizophrenic inpatients were included in the analysis and compared with a group of 20 healthy controls (HC). Data were collected with the computerised Wiener Testsystem measuring visual perception, reactivity and stress tolerance, concentration and vigilance. Analysis of data indicates that a great proportion (58 %) of schizophrenic patients were impaired in psychomotor functions related to driving skills. FES and RES significantly differed with respect to driving ability with a greater proportion in the FES (38 %) showing severe impairments when compared with RES (25 %). Differences with respect to HC performance were most pronounced in concentration and for the FES additionally in visual perception. Analysis of our data indicates that a great proportion of schizophrenic patients are impaired in psychomotor functions related to driving skills that cannot be attributed to adverse side effects of psychopharmacological treatment. Besides, we cannot confirm a chronical decline of psychomotor functions related to driving skills at least in the early course of schizophrenic illness.

Mobility behaviour and driving status of patients with mental disorders - an exploratory study.

BACKGROUND: Driving is an important activity of daily life and an integral part of mobility. However, impact of mental illness on road mobility is widely unexplored. METHOD: Driving status in 1497 psychiatric inpatients (PPs) and a clinical control group of 313 neurological inpatients (NPs) was investigated using a brief questionnaire. RESULTS: 67% of PPs (89% NPs) reported to have a valid driver's licence and 77% of them (92% NPs) reported to regularly use their cars. Within driver's license holders, patients with organic mental disorder (32%), substance dependence (37%) and psychotic disorder (40%) had the lowest proportion of current drivers. Higher educational qualification (odds ratio [OR] from 2.978 to 17.036) and being married/partnered (OR 3.049) or divorced (OR 4.840) significantly advanced the probability of possession of a driving license. Predictive factors for driving cessation were being female, an older age, drawing a pension and having an organic mental disease or schizophrenic disorder. CONCLUSION: Mental disease has a negative impact on driving status and this is especially true for illnesses frequently being accompanied by distinct cognitive impairments. Factors predicting road mobility elucidate the strong relationship with psychosocial status indicating that recovery of driving competence should be an integral goal of treatment strategies.

The effects of most commonly prescribed second generation antidepressants on driving ability: a systematic review : 70th Birthday Prof. Riederer.

Driving a car is vital for the functional autonomy of patients to take part in activities of daily living. Both psychopathologic symptoms and psychopharmacologic treatment may impair driving ability. This article provides a systematic review of published studies (1980-2011) on commonly prescribed newer antidepressants and driving performance. A total of 21 studies could be included in the review, indicating that there is a lack of controlled patient studies. Investigations on newer antidepressants were frequently undertaken in healthy subjects focusing on acute or subchronic effects of application, predominately in young male participants, with dosages usually given in an ambulatory setting. No data, according to selection criteria, were found with respect to agomelatine, duloxetine, bupropion and viloxazine. There is evidence that the SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, sertraline, paroxetine) and the SNRI venlafaxine have no deleterious effects on driving ability. Acute use of mirtazapine does produce impairments that diminish to some degree when given as a nocturnal dose and cannot be seen after repeated dosing in healthy controls. Patients obviously benefit from treatment with newer antidepressants; however, at least a subgroup does not reach performance level of healthy subjects. More patient studies are needed that elaborate specific relationships between clinical subtypes of the illness and response to different antidepressants, considering course and duration of illness, co-morbidities and not least neuropsychological and neurobiological characteristics.

Driving simulator performance and psychomotor functions of schizophrenic patients treated with antipsychotics.

The objective of the study is to compare schizophrenic inpatients under antipsychotic monotherapy regarding simulated driving behaviour and psychomotor functions related to driving ability. Schizophrenic inpatients (n = 80) were tested before discharge to outpatient treatment. Data were collected with the computerized Act & React Testsystem and the Wiener Testsystem measuring visual perception, reaction time, attention, vigilance and stress-tolerance. Besides, patients underwent various driving simulations on a static driving simulator (FT-SR 200). Before discharge to outpatient treatment, about 25% of schizophrenic patients must be considered as severely impaired with respect to driving skills. Differences between treatment groups could be shown both in psychomotor measures and in driving simulator performance with a better test performance of patients treated with atypical antipsychotics. Controlling for age, psychopathologic symptoms and extrapyramidal signs, differences in psychomotor measures were most pronounced in concentration and vigilance. As mental disorders itself pose an increased risk of accidents, counselling patients with respect to differential effects of antipsychotic treatment is of great relevance. In addition to psychomotor tests computer-simulated driving seems to be a useful tool in assessing traffic safety under pharmacologic treatment.

[Depression and response: impact of personality and cognition]. / Depression und Response: Der Einfluss von Persönlichkeit und Kognition.

OBJECTIVE: Despite effective pharmacologic and therapeutic strategies some patients do not sufficiently benefit from antidepressive treatment. The influence of personality and cognition onto response in depressive inpatients shall be explored. METHODS: Depressive inpatients were rated concerning depressive pathology immediately after admission as well as at discharge. In addition, prior to discharge, cognitive performance and personality traits were measured. The sample was divided into responders and nonresponders by the reduction of depressive symptoms from admission to discharge. For the assumption of response, a reduction of minimum 50 % was defined. RESULTS: Preliminary results suggest an impact of personality traits onto response in depressive patients, particularly extraversion seems to have a salutary effect. Furthermore, significant differences between responders and nonresponders were shown concerning alertness. CONCLUSIONS: In the treatment of non-response depression, cognitive and personality traits should be taken in account by using multimodal strategies.

The impact of reboxetine and mirtazapine on driving simulator performance and psychomotor function in depressed patients.

OBJECTIVE: The aim of the present study was to examine the influence of reboxetine and mirtazapine on psychomotor functions related to driving skills and on driving simulator performance in depressed inpatients. METHOD: Forty depressed inpatients diagnosed according to DSM-IV-TR criteria were randomly assigned to treatment with either reboxetine (N = 20) or mirtazapine (N = 20). To control for retest effects in psychomotor measures, a group of 10 healthy controls was examined on the same time schedule. Participants were tested once before pharmacologic treatment and twice after initiation of treatment (days 7 and 14) with computerized tests related to car-driving skills. Data were collected with the Act and React Testsystem ART-90 and the Wiener Testsystem, measuring visual perception, reactivity, stress tolerance, concentration, and vigilance. In addition, patients went through various risk simulations on a static driving simulator. Data were analyzed with nonparametric statistics and repeated-measures analysis of variance. The study was conducted from June 2004 through June 2006. RESULTS: Before onset of treatment with antidepressants, about 65% of patients did not reach the threshold criterion according to the German guidelines for road and traffic safety. After 14 days of treatment with reboxetine or mirtazapine, patients improved in driving ability skills. Controlling for retest effects in psychomotor measures, data indicate that both patient groups significantly improved in tests measuring selective attention and reactivity (all p < .01). Furthermore, the frequency of accidents in the risk simulations markedly decreased in patients receiving mirtazapine and reboxetine (all p < .05). Statistically significant differences between treatment groups could not be shown. CONCLUSION: Our results indicate that partially remitted depressed inpatients treated with reboxetine or mirtazapine show a better performance on tasks related to driving skills than do untreated depressives.

Antidepressants and driving ability: results from a clinical study.

OBJECTIVE: Psychomotor disturbances can frequently be found in depressed patients and may have an important influence on the ability to drive. Additionally, effects of sedation, as seen with some antidepressants, probably impair driving performance. The present study was designed to evaluate the effects of antidepressant monotherapy on psychomotor functions related to car-driving skills in depressive patients in a routine clinical setting. METHOD: Inpatients (N = 100) who met the ICD-10 and DSM-IV criteria for major depressive disorder were tested under steady-state plasma level conditions prior to being discharged to out-patient treatment. The study ran from January 2004 through March 2005. All patients participated voluntarily and gave informed consent. According to the German guidelines for road and traffic safety, data were collected with the computerized Act & React Testsystem ART-90 and the Wiener Testsystem, measuring visual perception, reaction time, selective attention, vigilance, and stress tolerance. Psychopathologic symptoms were rated with the Hamilton Rating Scale for Depression. RESULTS: Before discharge to outpatient treatment, 24% of the patients tested were without clinically relevant psychomotor disturbances. In 60% of the cases, mild to moderate impairments could be seen, and about 16% of the patients were considered as severely impaired in psychomotor functions related to car-driving abilities. Data show that patients treated with selective serotonin reuptake inhibitors (SSRIs) or the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine had an altogether better test performance in comparison with patients receiving tricyclic antidepressants (TCAs). Differences were most pronounced in measures of reactivity, stress tolerance, and selective attention. Statistically significant differences between patients treated with TCAs or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine could not be found. Among the newer antidepressants there is an advantage for patients treated with mirtazapine, especially in tasks with high multi-channel perception and output demands. CONCLUSION: About 16% of depressive patients discharged from hospital to outpatient treatment must be considered unfit to drive. In 60% of the cases, patients performed at a questionable level of fitness for driving, and it seems justified to counsel patients individually, taking into account compensational factors. Data point to an advantage for patients treated with SSRIs or mirtazapine when compared with TCAs or venlafaxine. However, causal relationships cannot be drawn from our data.

Driving ability in schizophrenic patients: effects of neuroleptics.

Recent studies indicate that individuals with schizophrenia have a two-fold incidence of traffic accidents. Cognitive and psychomotor impairment as a core feature of schizophrenia and the effects of neuroleptic treatment play an essential role in this respect. Few experimental studies have been conducted so far looking at the effects of neuroleptics on driving ability in schizophrenia. Controlled, randomised trials are totally missing. The limited database indicates that most schizophrenic patients show significant impairment in cognitive functions relevant for driving ability compared to healthy controls. There is some but limited evidence that patients under novel atypical neuroleptics show less impairment compared to conventional neuroleptics. More clinical and experimental studies are warranted.

[Antipsychotics and memory functions in schizophrenic patients]. / Antipsychotika und Gedächtnisleistungen schizophrener Patienten.

OBJECTIVE: The aim of this study was to evaluate the effects of antipsychotics on memory functions in schizophrenic patients under clinical routine conditions. METHOD: Schizophrenic patients (n = 111) before discharge to outpatient treatment were evaluated on verbal memory function. Data were analyzed according to pharmacological treatment controlling for age. RESULTS: We observed that treatment with atypical antipsychotics (n = 80) compared with conventional neuroleptics (n = 31) was significantly associated with a more favorable effect on memory function. In short-term- and working-memory and retention a clear advantage of atypical antipsychotics could be seen. CONCLUSIONS: Results from this study suggest that even under clinical routine conditions atypical antipsychotics have an advantage on memory function when compared with conventional antipsychotics.