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Tanja Veselinović,1,2 Ingo Vernaleken,1,2 Paul Cumming,3,4 Uwe Henning,5 Lina Winkler,1,2 Peter Kaleta,1,2 Michael Paulzen,1,2 Christian Luckhaus,6 Gerhard Gründer1,2,7 1Department of Psychiatry, Psychotherapy, and Psychosomatics, Faculty of Medicine, RWTH Aachen University, Aachen, 2Translational Brain Medicine, Jülich Aachen Research Alliance (JARA), Jülich, Germany; 3IHBI, School of Psychology and Counselling, Queensland University of Technology, 4QIMR Berghofer Institute, Brisbane, Australia; 5Neurobiochemical Research Unit, Department of Psychiatry, Heinrich Heine University, Düsseldorf, 6LWL University Hospital Bochum, Department of Psychiatry, Division of Cognitive Neuropsychiatry and Psychiatric Preventive Medicine, Ruhr University Bochum, Bochum, 7Department of Molecular Neuroimaging, Central Institute of Mental Health, Mannheim, Germany Objectives: Off-label prescription of antipsychotics to patients without psychotic symptoms has become a routine matter for many psychiatrists and also some general practitioners. Nonetheless, little is known about the possibly detrimental effects of antidopaminergic medications on general psychopathology, subjective mental state, or a possible association with physiological parameters in nonpsychotic individuals.Methods: In this randomized, single-blinded study, groups of healthy volunteers (n=18) received low doses of reserpine, aripiprazole, haloperidol, or placebo on 7 successive days. Relevant physiological parameters (plasma prolactin, concentrations of catecholamine metabolites in plasma, and 24-hour urine) and each subject’s mental state (Positive and Negative Syndrome Scale, Hamilton Rating Scale for Depression, visual analogue scale, Beck Depression Inventory II) were assessed at the start and end of the trial.Results: Of the three active treatments, only reserpine caused a significant increase in some plasma- and urine-catecholamine metabolites, but all three medications evoked objective and subjective changes in general psychopathology scores, which correlated with individual increases in plasma homovanillic acid concentrations. Both objective and subjective impairments were significantly more pronounced in the subgroup with greatest increase of plasma prolactin. Subjects experiencing the most pronounced side effects under haloperidol, which compelled them to drop out, showed significantly higher prolactin concentration increases than those who tolerated haloperidol well.Conclusion: We found consistent associations between altered markers of dopamine transmission and several objective and subjective mental impairments in healthy volunteers after 1 week’s treatment with antidopaminergic medications. These findings should draw attention to a more intensive risk–benefit evaluation in cases of off-label prescription of antipsychotic medications. Keywords: catecholamine metabolites, HVA, prolactin, dopamine, reserpine, aripiprazole, haloperidol, off-label prescription

With the introduction of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) numerous changes in the area of the schizophrenia spectrum and psychotic disorders have been implemented. Establishing a metastructure based on the characteristics of the spectrum of psychopathological disturbances should improve clarity. The classical subtypes of schizophrenia were eliminated and specific psychopathological dimensions for the assessment of disease severity were added. The special role of Schneiderian first rank symptoms was abandoned and a higher delineation towards schizoaffective disorders is made. The nosological status of catatonia is clarified and occurs together with a consistent use of catatonic disturbances over all chapters. The attenuated psychosis syndrome is added as a new condition for further study. The shared psychotic disorder in the sense of a folie à deux is no longer maintained. However, the initial goal to integrate more disorder-specific etiopathogenetic information into the reconceptualization could not be achieved. Contemporaneously to the development process of DSM-5 the National Institute of Mental Health (NIMH) carried out the research domain criteria project (RDoC) attempting to incorporate the current growth in knowledge of genetics, neurocognitive and cognitive sciences in future diagnostic systems. This article gives an overview of the changes that have been made within the revision process from DSM-IV to DSM-5.

According to the special report of the Advisory Council on the Assessment of Developments in the Health Care Sector, the termination of contracts on integrated care (IC) in accordance with §140a-d of the Social Act V (SGB V) was mostly due to high costs and volume expansion by services providers (physicians). However, there is still limited knowledge about the medical and economic impact of projects of integrated care, as such projects were on the one hand not primarily designed with a scientific evaluation in mind and on the other hand health insurance agencies usually do not evaluate data for scientific reasons.In Aachen the IC project "Integrated Care in Mental Health" ran between 2006 and 2011. During that time a total of 3,408 patients with depressive disorders were treated across institutional and trans-sectoral borders according to the national clinical practice guidelines and S3 guidelines on unipolar depression. This study was initiated in an attempt to describe and evaluate the clinical success of treatment.This study evaluated the outcome of the clinical treatment provided but due to the lack of available data on the economic impact of the project, the study contribution is limited to non-economic aspects. By comparing various clinical parameters it could be shown that scores in certain patient-reported clinical scales, such as the Hamilton rating scale for depression, and the WHO-5 well-being index as well as on the clinician-reported clinical global impression (CGI) improved in a statistically significant manner over time compared to initial assessments. Due to the lack of data on an appropriate comparison cohort of patients any comparative statements concerning the superiority of the treatment of depressive disorders outside an integrated care project remains hypothetical and preliminary.This study revealed the limitations of a naturalistic study in an IC setting and showed that without adequate funding a satisfactory evaluation that fulfills scientific criteria seems to be impossible.