The right to make autonomous decisions is enshrined in law. However, the question how persons with cognitive deficits can be enabled to make autonomous decisions has not been satisfactorily addressed. In particular, the concept of supported decision-making and its implementation into practice has been poorly explored for persons with dementia (PwD).This article describes the empirical development and implementation of support tools to enhance informed consent processes (so called enhanced consent procedures/ECP) for PwD on whether to undergo lumbar puncture. In the end of the process of pilot testing and further development of the tools, the following tools were defined: (1) Standardized Interview Structure, (2) Elaborated Plain Language, (3) Ambience and Room Design, (4) Keyword Lists, (5) Priority Cards, (6) Visualization, and (7) Simplified Written Informed Consent (Patient Information), as well as the general attitude (8) Person-Centered Attitude of the facilitator. As the development, implementation and evaluation of ECP tools is one objective of the transnational ENSURE project, we also include an overview of future empirical procedures. So far, our findings can serve as a selection of possibilities to support PwD in decision-making and help practitioners achieve an appropriate balance between the autonomy and protection of PwD in complex decision-making situation. Future studies should address the question if the proposed set of tools is effective to enhance informed consent processes in PwD.

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Despite its continued relevance as the single most effective and important evidence-based treatment for schizophrenia, the degree of underutilization of clozapine across health systems remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to use clozapine due to its relatively large side-effect burden and its comparatively complex dosing and monitoring requirements. This underscores the necessity for continued education of clinicians in the intricacies of clozapine use and in the still growing case in favor of this vital treatment option. Consequently, this narrative review provides a comprehensive outline of all lines of evidence, which support clozapine’s wide-ranging superior efficacy, and of the current knowledge regarding the prevalence and diagnosis of treatment resistance. The distinct neurobiological and clinical characteristics of this condition makes the swift initiation of clozapine indispensable. Moreover, we review the extensive literature regarding clozapine’s side effect profile and current recommendations for optimal treatment and monitoring algorithms including for particularly vulnerable populations such as elderly patients and pregnant women and for potential re-challenges after myocarditis and neutropenia. We also discuss established approaches to increase treatment response as well as augmentation strategies for patients with partial or full clozapine resistance. We argue for a clear focus on early and consistent detection and management of side effects, which can ensure patient safety and reduce permanent all-cause discontinuation. This strategy needs to be combined with a long-term approach acknowledging the late onset of clozapine’s full advantageous effects, which – in cases like reduced mortality rates – even then may not be easily discernible. Our aim is to encourage a safer, more frequent, and timely use of clozapine to maximize patients’ short- and long-term benefits. Even now, the extent of these benefits as well as patient’s satisfaction with treatment still clearly set clozapine apart from all other available treatment options.

A still expanding body of evidence unequivocally supports the superior efficacy of clozapine compared to other antipsychotics for a considerable number of outcome measures in the treatment of schizophrenia including positive symptoms, negative symptoms, aggression and suicidality. Therefore, clozapine remains the gold standard not only for treatment-resistant schizophrenia but also for a larger number of patients with a poor course of illness. Furthermore, recent meta-analytical evidence clearly demonstrates the superiority of clozapine for reducing all-cause mortality. This finding indicates that clozapine is one of the most potent means to reduce the outrageous mortality gap faced by patients with schizophrenia. Despite its unmatched and wide-ranging efficacy as well as its cost effectiveness, clozapine remains alarmingly underutilized throughout the industrialized world even though patients’ acceptance of clozapine treatment is surprisingly high. While limited, existing evidence indicates that this is primarily due to psychiatrists’ concerns regarding safety and side effect management possibly resulting from insufficient clinical training in using clozapine. This would imply that many patients are never offered clozapine in the first place despite a clear indication. We argue that psychiatrists have an urgent obligation to address this issue and ensure sufficient availability of this vital treatment option. If our fields’ commitment to shared decision-making is to be genuine, we must not exclude patients from the potentially life-changing decision to initiate clozapine treatment. Therefore, concerted research and mental-health policy efforts should focus on identifying barriers for clozapine utilization and effective measures to overcome them. On the one hand, this will require structural changes to clinical training and care systems. On the other and hand – and at least as important – it will require a continued commitment of individual psychiatrists to align their attitudes and clinical practices more closely with the existing evidence and patient preference. The benefits for patients, their families, clinical psychiatry and society will be substantial.

Despite its enduring relevance as the single most effective and important evidence-based treatment for schizophrenia, underutilization of clozapine remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to offer clozapine due to its relatively large side-effect burden and the complexity of its use. This underscores the necessity for continued education regarding both the vital nature and the intricacies of clozapine treatment. This narrative review summarizes all clinically relevant areas of evidence, which support clozapine’s wide-ranging superior efficacy – for treatment-resistant schizophrenia (TRS) and beyond – and make its safe use eminently feasible. Converging evidence indicates that TRS constitutes a distinct albeit heterogeneous subgroup of schizophrenias primarily responsive to clozapine. Most importantly, the predominantly early onset of treatment resistance and the considerable decline in response rates associated with its delayed initiation make clozapine an essential treatment option throughout the course of illness, beginning with the first psychotic episode. To maximize patients’ benefits, systematic early recognition efforts based on stringent use of TRS criteria, a timely offer of clozapine, thorough side-effect screening and management as well as consistent use of therapeutic drug monitoring and established augmentation strategies for suboptimal responders are crucial. To minimize permanent all-cause discontinuation, re-challenges after neutropenia or myocarditis should be considered. Owing to clozapine’s unique efficacy, comorbid conditions including substance use and most somatic disorders should not dissuade but rather encourage clinicians to consider clozapine. Moreover, treatment decisions need to be informed by the late onset of clozapine’s full effects, which for reduced suicidality and mortality rates may not even be readily apparent. Overall, the singular extent of its efficacy combined with the high level of patient satisfaction continues to distinguish clozapine from all other available antipsychotics.

Studying the visual system with fMRI often requires using localizer paradigms to define regions of interest (ROIs). However, the considerable interindividual variability of the cerebral cortex represents a crucial confound for group-level analyses. Cortex-based alignment (CBA) techniques reliably reduce interindividual macroanatomical variability. Yet, their utility has not been assessed for visual field localizer paradigms, which map specific parts of the visual field within retinotopically organized visual areas. We evaluated CBA for an attention-enhanced visual field localizer, mapping homologous parts of each visual quadrant in 50 participants. We compared CBA with volume-based alignment and a surface-based analysis, which did not include macroanatomical alignment. CBA led to the strongest increase in the probability of activation overlap (up to 86%). At the group level, CBA led to the most consistent increase in ROI size while preserving vertical ROI symmetry. Overall, our results indicate that in addition to the increased signal-to-noise ratio of a surface-based analysis, macroanatomical alignment considerably improves statistical power. These findings confirm and extend the utility of CBA for the study of the visual system in the context of group analyses. CBA should be particularly relevant when studying neuropsychiatric disorders with abnormally increased interindividual macroanatomical variability.

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

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