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Background: Blinded placebo treatment arms in clinical trials often achieve up to 80% of the clinical improvements of the verum groups. Apparently, the majority of the effects found in the antidepressant groups in clinical trials are due to factors that are not specific to antidepressant treatment. This article reviews the factors that contribute to the high effectiveness of placebo interventions for antidepressants.

Methods: A narrative literature review is presented with particular emphasis on placebo effects in antidepressant clinical trials.

Results: There is a particularly strong placebo effect in depression compared to other mental disorders. The magnitude of this effect can be modulated by helpful versus nonhelpful instructions, by patient participation in the decision-making process but also by personal attention, especially if the clinician is perceived as competent and warmhearted. The occurrence of subtle side effects can also reinforce placebo effects. Placebo effects are not only reflected in subjective patient-reported outcome variables but are also evident in neurochemical changes in the body.

Conclusion: Clinicians essentially contribute to the effectiveness of antidepressant treatment through their own behavior. At the same time, the relatively small overall difference between verum and placebo treatments for depression leads to the necessity of a critical evaluation of the cost-benefit ratio, adapted to the individual case. Study designs for the evaluation of antidepressants are required that better reflect the complex interactions between the genuine drug effects and placebo effects.

Background: Antidepressant pharmacotherapy often does not result in the desired effect despite adequate duration and dose. Better evidence on second-step strategies is needed.

Objective: Overview of the current evidence for various pharmacological second-step strategies after nonresponse to antidepressant monotherapy.

Material and methods: Summary of recent systematic reviews with meta-analyses of the group of authors on pharmacological second-step treatment.

Results: A meta-analysis showed no advantage of switching to a second antidepressant compared with continuing the previously ineffective monotherapy. Another two meta-analyses showed no benefit of increasing the dose of selective serotonin reuptake inhibitors (SSRI). For serotonin and noradrenaline reuptake inhibitors (SNRI) and tricyclic antidepressants (TCA) in each case a meta-analysis showed no clear advantage of increasing the dose. Another two meta-analyses showed a superiority of a combination therapy consisting of a reuptake inhibitor (SSRI, SNRI, TCA) with a presynaptic alpha‑2 autoreceptor antagonist (e.g., mirtazapine) compared with an antidepressant monotherapy.

Conclusion: In accordance with the recommendations of the German national treatment guideline, in the event of nonresponse to antidepressant monotherapy, the combination of two antidepressants is preferable to repeated switching of the antidepressant.

Neurorehabilitation is characterized by a structured, interdisciplinary collaboration among various professional fields, focused on achieving individualized participation goals for patients. This process considers the different levels of the International Classification of Functioning, Disability, and Health (ICF), specifically function, activity and participation. Multiple evidence-based treatment procedures targeting specific mechanisms of action are available for the rehabilitation of disorders associated with various diseases. Treatment must be administered with sufficient intensity to be effective. The neurological phase model encompasses several stages of care ranging from acute treatment in phase A to phase D for patients who are largely independent. Early rehabilitation phase B and rehabilitation phase C combine acute and rehabilitation-specific tasks. Phase E supports long-term occupational and social participation, while phase F is dedicated to long-term care for severely affected patients. In the outpatient setting, the long-term care of neurologically affected patients remains insufficient due to a lack of interdisciplinary collaboration possibilities, highlighting an urgent need for expansion and improved integration between care providers.

Background: The high number and clinical heterogeneity of neurological impairments in patients with a post-COVID-19 condition (PCC) poses a challenge for outpatient care.

Objective: Our aim was to evaluate the applicability of the proposed subtypes according to the guidelines "Long/Post-COVID" (30 May 2024) and their phenotyping using clinical and neuropsychological findings from our post-COVID outpatient clinic.

Methods: The evaluation was based on cross-sectional neurological and psychological test examinations of the patients, which were carried out using standardized questionnaires and test batteries. In addition, a detailed anamnesis of the current symptoms and a retrospective survey of the acute symptoms up to 4 weeks after the confirmed infection was conducted. The subtypes were classified according to the abovementioned guidelines based on the medical history and selected patient questionnaires, to which we added a 5th subtype with reference to the previous guidelines "Long/Post-COVID" (as of 5 March 2023).

Results: A total of 157 patients were included between August 2020 and March 2022. The presentation was at a median of 9.4 months (interquartile range, IQR = 5.3) after infection, with a mean age of 49.9 years (IQR = 17.2) and more women (68%) presenting, with a total hospitalization rate of 26%. Subtype 1 (postintensive care syndrome) showed the highest proportion of men, highest body mass index (BMI) scores and the highest rates of subjective complaints of word-finding difficulties (70%). Subtype 2 (secondary diseases) was dominated by cognitive impairment and had the highest depression scores. Subtype 3 (fatigue and exercise-induced insufficiency) was the most common, had the most symptoms and most severe subjective fatigue and the largest proportion of women. Subtype 4 (exacerbation) mainly showed affective symptoms. Subtype 5 (complaints without relevance to everyday life) had the lowest scores for depression, fatigue and BMI. Neurological and psychological conditions were frequently pre-existing in all groups.

Discussion: The management of PCC can be improved at various levels. A standardized subtype classification enables early individually tailored treatment concepts. Patients at risk should be identified at the primary care level and informed about risk factors and prevention strategies. Regular monitoring of cardiovascular risk factors and physical activity are essential for PCC treatment. In the case of cognitive deficits and concurrent affective symptoms, psychotherapeutic support and drug treatment with selective serotonin reuptake inhibitors (SSRI) should be provided at an early stage.

Background: Amyotrophic lateral sclerosis (ALS) is a disease that still has to be primarily treated symptomatically or palliatively. It is therefore all the more important, in addition to initiating treatment, such as percutaneous endoscopic gastrostomy (PEG), noninvasive ventilation therapy (NIVT) and invasive ventilation therapy via tracheotomy (IVT), to discuss the possible termination of these measures early on.

Question: What is the importance of advance directives for those affected and where are possible deficits in therapy planning for the end of life?

Material and method: Between March 2017 and January 2019 patients with a clinically confirmed diagnosis of ALS at six treatment centers were asked to fill out a questionnaire. A total of 328 people returned the completed forms.

Results: Of the participants 72% had already made an advance directive (AD), 25% planned to fill one out and only 3% refused to do so. In composing the AD most patients (90%) had support, although 56% lacked medical counselling and only 18% had drawn up the will together with the doctor and relatives, with the majority of the rest also wanting support from a doctor. A total of 37% of all patients wanted a contact person to talk about their illness but only 40% of them had such a contact person. Of the patients 22% stated that they had considered suicide and of these only 55% stated that they had no contact person for the psychological stress caused by the illness but 31% wished to have such a person.

Discussion and conclusion: A coordinated care of ALS patients, which also takes the psychosocial aspects into account is urgently needed.

Background: Approximately two thirds of patients with epilepsy become seizure-free with antiseizure medication (ASM). A central question is whether and when ASM can be discontinued.

Objective: To present an overview of the current knowledge about risks and benefits of discontinuation of ASM.

Material and methods: Review of the current literature, discussion of data on and recommendations for discontinuation of ASM.

Results: The risk of seizure recurrence after discontinuation of ASM is approximately 40-50% and thus twice as high as continuing with ASM. Guidelines recommend considering discontinuation of ASM at earliest after a seizure-free period of 2 years. Predictive variables for seizure recurrence after stopping ASM include longer duration of epilepsy and higher number of seizures until remission, a shorter seizure-free interval until stopping ASM, older age at epilepsy onset, developmental delay or IQ < 70, febrile seizures in childhood, absence of a self-limiting epilepsy syndrome, and evidence of epileptiform activity in the electroencephalograph (EEG). The individual risk of seizure recurrence after stopping ASM can be estimated using an online prediction tool.

Conclusion: Discontinuation of ASM should be discussed with patients at the earliest after 2 years of seizure freedom in a shared decision-making process weighing up the risks and benefits. The risk of a seizure recurrence depends on a number of clinical variables. Psychosocial aspects, such as impact on driving and occupational issues must be taken into consideration as well as individual fears and concerns of patients about seizure recurrence or the long-term use of ASM.

Background: For the treatment of the symptoms of post-COVID-19 syndrome, no causal therapy is currently widely recommended according to evidence-based criteria. The overarching goal of the intervention study over a 3-year period (Q1-2021-Q4-2023) was to evaluate the changes in the key symptoms of fatigue and sensorimotor instability through individualized stress-controlled training therapy and through intensified cognitive behavioral therapy.

Material and methods: In the 3‑year period 407 vaccinated nucleocapsid positive patients were treated at the Post-COVID-19 Center Lausitz (Senftenberg). In 78 (around 19%) fatigue/immunometabolic depression and sensorimotor instability were identified as the leading syndromes. The evaluation of the individualized stress-controlled training therapy was based on the specific post-COVID-19 syndrome and motor fatigue parameters. The secondary psychosomatic syndrome was assessed using cognitive fatigue parameters and cognitive behavioral therapy instruments. The investigation of -parameters influencing behavior took place in Q2-2023-Q4-2023 with a guide-supported qualitative interview among the participants.

Results: The post-COVID-19 key symptoms "fatigue," "sensorimotor instability," "neuropsychiatric symptoms," "cardiac/autonomic dysfunction," and "pain" improved significantly in the overall cohort and in the gender-specific analysis. A deterioration occurred in "secondary psychosomatic symptoms". A therapeutic effect was demonstrated for all motor fatigue parameters for the entire cohort using the Cohen's d value. An intensification of cognitive behavioral therapy achieved positive effects through an increasing development of the patients' own activity and their self-control using persuasion and gamification.