BackgroundIn this study, the treatment of schizophrenia patients with aripiprazole once-monthly (AOM) was evaluated under real-life conditions in a naturalistic setting.MethodsThis multicenter, prospective, non-interventional study included 242 patients (age = 43.1 ± 15.1 years, 55.0% male) who were monitored during 6 months of AOM treatment. Endpoints included measurements of psychopathology (Brief Psychiatric Rating Scale, BPRS) and severity of illness scales (Clinical Global Impressions-Severity, CGI-S, and -Improvement, CGI-I). Furthermore, treatment-related adverse events (TRAEs) were recorded.ResultsAt baseline, the mean BPRS total score was 54.1 ± 15.6, the mean CGI-S was 4.8 ± 0.8 and the most frequent illness category was ‘markedly ill’ (41.7%). Patients had been pretreated with oral aripiprazole for a mean duration of 9.7 months (SD: 22.3) and 87.9% were deemed by their clinician as “clinically stable” and for a mean of 5.9 months. The difference in global BPRS after 6 months was − 13.8 (SD: 16.0; 95% CI: [− 15.9; − 11.7]; p < 0.001). The proportion of patients with high CGI-S scores decreased and the proportion of patients with low scores increased significantly (p < 0.001, respectively). BPRS scores improved numerically especially well in younger patients ≤35 years, CGI-S scores decreased significantly more in this population. TRAEs were rare, with low incidences of extrapyramidal symptoms (2.9%) or weight increase (0.4%).ConclusionsTreatment with AOM showed satisfying effectiveness in outpatients with further improvement of psychopathology after oral aripiprazole treatment for a considerable duration and even after having achieved clinically judged “stability”. Our findings indicate a robust therapeutic effect of AOM and substantiate previous results from randomized controlled trials under real-world routine conditions.

Treatment with memantine delays clinical worsening in patients with moderate to severe AD when compared with placebo. This effect was seen in single domains (cognition, functional abilities and clinical global impression) as well as in the combination of these domains. The consistent results prove the beneficial effects of memantine in moderate to severe AD patients.

Background: Non-interventional naturalistic studies are an important complement to randomized controlled trials. Aripiprazole once-monthly (AOM) is an atypical antipsychotic in a long-acting injectable formulation.Methods: A pooled analysis of 2 non-interventional studies was undertaken to validate previous results on AOM effectiveness and safety in a larger population and improve statistical power for pre-planned subgroup analyses. We analyzed data from 409 patients with schizophrenia who were treated with AOM and were enrolled in non-interventional studies in Germany (vfa non-interventional studies registry 15960N) and Canada (NCT02131415). Data collected at baseline, 3 months and 6 months were analyzed.Among the endpoints were psychopathology (Brief Psychiatric Rating Scale, BPRS) and disease severity (Clinical Global Impression, CGI).Results: Mean patient age was 38.9 (SD 14.8) years, and 59.9% were male. BPRS decreased from 48.1 (SD 15.6) at baseline to 36.5 (SD 13.7) at month 6 (p < 0.001). CGI decreased from 4.47 (SD 0.90) at baseline to 3.64 (SD 1.16) at month 6 (p < 0.001). 54.4% were responders (at least 20% reduction) on the BPRS, and 56.4% had a CGI-S-score that was at least 1 level better than baseline. 43.4% were considered responders on both the BPRS and CGI scales. 45.2% were considered in remission. Adverse events were rare and corresponded to the previously known safety profile of AOM.Conclusions: Treatment with AOM for patients with schizophrenia appeared effective and safe under real-life conditions.

Background: In this non-interventional study, the functionality and well-being of patients with schizophrenia with aripiprazole once-monthly (AOM) was evaluated under real-life conditions in a naturalistic population. Methods: This non-interventional, prospective, multicenter 6-month study included 242 predominantly symptomatically stable patients (mean age 43.1 ± 15.1 years, 55% male) who switched their treatment to AOM after 9.7 (± 22.3) months of oral treatment. Outcome parameters included functionality (Global Assessment of Functioning, GAF), patient's wellbeing (WHO-5 Well-Being Index, WHO-5), and both patient's and clinician's assessment of efficacy and tolerability of AOM. Treatment emergent adverse events (TRAE) were also recorded. Results: At baseline, the mean GAF score was 47.0 (±13.9), indicating that patients experienced serious impairment in functioning. A continuous increase to 60.2 (±17.0) during treatment was found, with a robust and significant increase already after 4 weeks. At study start, patients reported diminished wellbeing, with a mean score of 10.6 (±5.6) on the WHO-5 scale. During treatment, patient wellbeing increased continuously with strong and significant improvements even after 4 weeks and an overall improvement of 4.8 (±6.9) over the course of 6 months with an endpoint of 15.4 (± 5.5). Stratification of these results showed that more pronounced effects were achieved in younger patients ≤35 years (p<0.05 for GAF). The effectiveness and tolerability of AOM was rated good/very good by most patients (89.2 and 93.7%) and physicians (91.4 and 96.8%). Only few TRAEs occurred. Conclusions: Our results show a significant positive effect after initiation of AOM treatment in predominantly stable patients with schizophrenia on their functioning and wellbeing, which was even more pronounced in patients aged ≤35 years, thereby supporting previous randomized controlled findings under routine conditions in clinical practice.

Background/Aims: Global cognitive scales and meta-analyses thereof are used to appraise therapeutic efficacy over a broad range of disease severity. Clinically, however, different aspects of cognition change in different stages of disease. Methods: Calculation of effect sizes for single cognitive functions on treatment as assessed by the Alzheimer’s Disease Assessment Scale (ADAS-cog), the Mini-Mental-Status Examination (MMSE), and the Severe Impairment Battery (SIB). In these scales, subdomains of ‘cognition’, e.g. memory and language, are represented in different proportions. To exemplify the analysis of ‘cognition’, we used original data of previously published clinical studies with memantine. Results: Depending on dementia severity and on the scale used, the effect size for memory varies between –0.44 and +0.34 and for language between –0.40 and +0.26. Conclusion: Beyond interstudy variance, effect sizes for treatment with antidementia drugs are subject to disease stage, instruments used, and interaction thereof. Therefore, clinical interpretation is necessary to appraise therapeutic efficacy in clinical studies and meta-analyses thereof when patients with different severity are included or different instruments are used. Alternatively, severity-adapted endpoints should be used for appraisal and meta-analysis of therapeutic efficacy.

Background/Aims: Results from German and Greek non-interventional studies were compared to investigate possible differences concerning efficacy, tolerability and compliance between both countries. Methods: In two open-label, multicentre, non-interventional studies, 4,305 patients with mild to severe Alzheimer’s disease (AD) were treated with daily doses of 20 mg memantine for 6 months. Efficacy was assessed using the Mini-Mental State Examination (MMSE) and instrumental activities of daily living (IADL) scales. Safety and tolerability were recorded. Results: After 6 months, the patients showed an improvement of their cognitive performance by 2 MMSE points compared to baseline (p < 0.001). MMSE values were improved in 67.4% of the patients, while 15.1% remained stable, and MMSE deteriorated in 17.5% only. The ability to perform IADL increased, as is indicated by lower values (baseline: 70.5; after 6 months: 66.6 points). Improvement of cognition and IADL was nearly identical in both countries. Treatment discontinuation was significantly more frequent in the Greek population, mainly due to non-adherence (9.4% of the safety population). 345 adverse events were recorded in 245 patients (6.3%), and they were significantly associated with country and age. Conclusion: The results correspond to those of clinical trials and support the efficacy and good tolerability of memantine in a realistic setting. Differences between the countries were observed regarding the baseline characteristics of patients (more female, older and more severe patients in Germany as well as less pretreatment with cholinesterase inhibitors) and regarding premature discontinuation and reported adverse drug reactions, which were both higher in Greece.

ZusammenfassungDie Berücksichtigung der Lebensqualität hat sich in den in den letzten 50 Jahren zu einem wichtigen Konzept einer patientenorientierten Medizin entwickelt. Mit ihm soll das subjektive Erleben der Patienten erfassbar und in seinen verschiedenen Dimensionen beschreibbar gemacht werden. Heute ist die Lebensqualität als patientenberichteter Endpunkt auch integraler Bestandteil der frühen Nutzenbewertung nach dem Arzneimittelmarkt-Neuordnungsgesetz (AMNOG). In der Therapie schizophrener Patienten hat sich die Verbesserung der Lebensqualität als akzeptiertes Zielkriterium allerdings erst mit Verzögerung etabliert.

ZUSAMMENFASSUNG Hintergrund Bei Patienten mit Störungen aus dem schizophrenen Formenkreis ist der Konsum von Cannabis und anderen psychoaktiven Substanzen weit verbreitet. Es besteht eine wissenschaftliche Evidenz, dass der hochdosierte und regelmäßige Freizeitkonsum von Cannabis mit nachteiligen Langzeitfolgen assoziiert ist. Und dennoch könnte die physiologische Bedeutung des Endocannabinoidsystems (ECS) den Einsatz von Cannabispräparaten – womöglich mit einem hohen Gehalt an Cannabidiol (CBD) – zur Therapie neuropsychiatrischer Erkrankungen als nützlich erscheinen lassen. Ziel Darstellung der Grundlagen für die Wirksamkeit von medizinischem Cannabis bei neuropsychiatrischen Erkrankungen – insbesondere Störungen aus dem schizophrenen Formenkreis – und kritische Nutzen-Risiko-Bewertung. Ergebnisse und Diskussion Die beiden wichtigsten neuroaktiven Bestandteile von Cannabis sind CBD und Tetrahydrocannabinol (THC). THC scheint psychose- und angstfördernd zu wirken und die Kognition zu beeinträchtigen. Basierend auf einer Recherche aktueller Literatur ist anzunehmen, dass CBD im Gegensatz zu THC nicht euphorisierend, sondern antikonvulsiv, analgetisch, angstlösend und antipsychotisch wirken könnte und möglicherweise die kognitive Leistungsfähigkeit verbessern kann. Somit wäre CBD ein natürlicher Antagonist von THC. Während es eine hinreichende Evidenz gibt, dass der Freizeitkonsum von meist THC-lastigem Cannabis die psychische Gesundheit nachteilig beeinflusst und Psychosen fördert, gibt es Studien, die darauf hindeuten, dass CBD protektiv sein könnte. Allerdings mangelt es an hochwertigen kontrollierten klinischen Studien mit größeren Patientenzahlen und guter Methodik, um eine ausreichende Evidenz für den Einsatz von Cannabidiol in der klinischen Praxis zu begründen.