Symptomatic, functional and quality of life measures of remission in 194 outpatients with schizophrenia followed naturalistically in a 6-month, non-interventional study of aripiprazole once-monthly.

An important goal in the treatment of patients with schizophrenia is remission in various domains, i.e., of symptoms, psychosocial functioning and subjective well-being. We undertook a post hoc analysis of pre-stabilized outpatients with schizophrenia and complete outcome data who had been enrolled in a 6-month non-interventional study of aripiprazole once-monthly (AOM) at 75 German sites. Key outcomes were (i) symptomatic remission (cross-sectional Andreasen et al. criteria (≤mild positive and negative key symptoms on the Brief Psychiatric Rating Scale (BPRS))); (ii) functional remission (Global Assessment of Functioning (GAF) scale score >70), and (iii) subjective well-being remission (WHO-5 scale score ≥13) at week 24. Of 242 enrolled patients, 194 (80.2%) (age = 43.9 ± 15.3 years; 51.5% male, illness duration = 14.0 ± 12.0 years) with complete data were analyzed. While 61.3% of the patients achieved symptomatic remission and 76.8% achieved remission regarding subjective well-being, only 24.7% achieved psychosocial functioning remission at 6 months. Remission rates were similar for men and women and across strata of disease duration with, on average, less remission in patients with longer illness duration. Correlations of improvements on the BPRS and GAF were weak, with the weakest correlation between the BPRS depressive mood item and the GAF scale, but similarly high correlation between BPRS subscales or the BPRS depressive mood item and subjective well-being. These findings suggest that while treatment with AOM can lead to symptomatic remission and remission regarding subjective well-being, additional interventions such as psychosocial therapy or supported employment and education may be necessary to achieve functional remission.

Improvement of functioning in patients with schizophrenia: real-world effectiveness of aripiprazole once-monthly (REACT study).

BACKGROUND: Functional impairment affects many patients with schizophrenia. Treatment with the long-acting injectable antipsychotic aripiprazole once-monthly (AOM) may help improve functioning. OBJECTIVES: To explore changes in functioning in patients with schizophrenia who received AOM treatment in observational studies. METHODS: Here we report functional outcomes in the form of Global Assessment of Functioning (GAF) scores in a pooled analysis of data from two observational studies from Canada (NCT02131415) and Germany (vfa non-interventional studies registry 15960N). Data from 396 patients were analyzed. RESULTS: At baseline, the mean GAF score was 47.7 (SD 13.4). During 6 months of treatment with AOM, the mean GAF score increased to 59.4 (SD 15.8). Subgroups stratified by patient age (≤35 years/>35 years), sex, disease duration (≤5 years/>5 years) and disease severity at baseline had all significantly improved their GAF at month 6. 51.5% of the patients showed a GAF score increase of at least 10 points, which was regarded as clinically meaningful, and were considered responders. CONCLUSIONS: These data show that treatment with AOM may help improve patient functioning in a routine treatment setting. TRIAL REGISTRATION: NCT02131415 (May 6, 2014), vfa non-interventional studies registry 15960N.

BPRS domains, items and subgroups analyses, and CGI-I ratings in pooled data from non-interventional studies of aripiprazole once-monthly in schizophrenia (REACT study).

BACKGROUND: Patients with schizophrenia may benefit from treatment with long-acting injectable (LAI) formulations of antipsychotics. Aripiprazole once-monthly (AOM) is an LAI that was tested in two non-interventional studies in Germany and Canada. METHODS: Here, we report on analyses of pooled data from the two non-interventional studies. Patients were treated with AOM under real-life conditions. Data were analyzed for a timeframe of 6 months. We analyzed data on Brief Psychiatric Rating Scale (BPRS) domains and items, BPRS total scores in various patient subgroups (male vs. female patients, patients with disease duration ≤ 5 years and > 5 years, patients with different levels of disease severity at baseline), Clinical Global Impression - Improvement (CGI-I) ratings for the total population and subgroups, and comorbidities for the total population. RESULTS: Data from 409 patients were included. 65.5% of the patients had comorbidities. Improvements were found in all BPRS domains and items. Furthermore, improvements were similar for male and female patients, patients with disease duration ≤ 5 years and > 5 years, and across different levels of disease severity at baseline. Numerically, more favorable results were found for younger patients, female patients, and those with shorter disease duration. CONCLUSIONS: AOM can be an effective treatment in the broad range of patients, across sexes, regardless of patient age and duration of disease, independently of disease severity, and across symptoms. TRIAL REGISTRATION: NCT02131415 (May 6, 2014), vfa non-interventional studies registry 15960N.

Real-world effectiveness of aripiprazole once-monthly REACT study: Pooled analysis of two noninterventional studies.

BACKGROUND: Noninterventional 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 two noninterventional studies was undertaken to validate previous results on AOM effectiveness and safety in a larger population and improve statistical power for preplanned subgroup analyses. We analyzed data from 409 patients with schizophrenia who were treated with AOM and were enrolled in noninterventional studies in Germany (via noninterventional studies registry 15,960 N) and Canada (NCT02131415). Data collected at baseline, 3 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). A total of 54.4% were responders (at least 20% reduction) on the BPRS, and 56.5% had a CGI-S-score that was at least 1 level better than baseline. A total of 43.4% were considered responders on both the BPRS and CGI scales. A total of 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.

[Early Intervention in Schizophrenia - an Update]. / Frühintervention bei Schizophrenie ­ ein Update.

In Germany, psychoses are still diagnosed too late. The average duration of untreated psychosis is (DUP) one year. Early intervention should, therefore, be given higher priority. The shorter the duration of the DUP, the higher the probability of permanent recovery and a better long-term prognosis. Public education work and specialised early detection centres with low-threshold access can improve care and thus the prospects of patients, mostly young, and already in the early phase of the disease. In addition to anti-psychotic therapy, evidence-based psychotherapeutic procedures, family and peer work, as well as accompanying offers are necessary to support patients individually in being or remaining reintegrated into the labour market ("Individual Placement and Support", IPS). While in some countries, such as Denmark and Australia, the possibility of early intervention is already part of standard care, Germany has not yet gone beyond model projects. Changing this must be one of the main objectives for the coming years. With this review, the authors would therefore like to encourage further thinking and action.

The use of long-acting Aripiprazole in a multi-center, prospective, uncontrolled, open-label, cohort study in Germany: a report on global assessment of functioning and the WHO wellbeing index.

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.

[Motivational interviewing : A possibility for doctor-patient communication in schizophrenia?] / "Motivational interviewing" : Eine Möglichkeit der Arzt-Patienten-Kommunikation bei Schizophrenie?

Motivational interviewing (MI) has become established nowadays as an approach for a cooperative style of conversation to promote intrinsic motivation for change by exploring and resolving ambivalences. The change of addictive behavior is no longer sought by exerting pressure or lecturing/converting attempts of convincing or persuasion but by activating existing but "buried" or newly acquired self-motivation to change. The MI is now also used to change the treatment of other health-related behavior and chronic diseases, including schizophrenic disorders. Compared to the efficacy of MI in the addiction area, the data situation in schizophrenic patients is still insufficient. According to the available studies, MI can positively influence important aspects of disease-related impairments, such as medication adherence, the frequency and severity of psychotic relapses, the duration of hospitalization, the level of function, insight into the disease and cognitive rehabilitation. The practical implementation of MI requires a good knowledge of the method as well as changes in treatment principles and work processes.

[Quality of life as a target criterion in schizophrenia therapy]. / Lebensqualität als Zielkriterium in der Schizophrenietherapie.

Consideration of quality of life has developed into an important concept of a patient-oriented medicine in the last 50 years. With it, it should be possible to capture the subjective experience of the patients and describe its different dimensions. Today, the quality of life as a patient-reported endpoint is also an integral part of the early benefit assessment under the German Drug Market Reorganization Act. In the treatment of schizophrenic patients, however, improvement in quality of life as an accepted target criterion has only been established with delay.

Correction to: Effectiveness of aripiprazole once-monthly in schizophrenia patients pretreated with oral aripiprazole: a 6-month, real-life non-interventional study.

Following publication of the original article.

Effectiveness of aripiprazole once-monthly in schizophrenia patients pretreated with oral aripiprazole: a 6-month, real-life non-interventional study.

BACKGROUND: In this study, the treatment of schizophrenia patients with aripiprazole once-monthly (AOM) was evaluated under real-life conditions in a naturalistic setting. METHODS: This 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. RESULTS: At 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%). CONCLUSIONS: Treatment 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.

Efficacy of memantine in delaying clinical worsening in Alzheimer's disease (AD): responder analyses of nine clinical trials with patients with moderate to severe AD.

OBJECTIVE: Responder analyses are of relevance to evaluate the benefits of a medical treatment. The aim of the current paper is to analyse the response of patients with moderate to severe Alzheimer's disease (AD) to memantine, and clinical relevant response is defined as a delay of clinical worsening. METHODS: Post hoc analyses were performed over the results of nine individual clinical trials including 2506 study patients. Overall, estimates of the odds ratio (OR) and corresponding confidence intervals were based upon a random-effect model for three individual domains (cognition, activities of daily living and clinical global impression). In addition, a combined responder criterion (triple response) includes all three individual domains. RESULTS: Responder analyses have shown that AD patients treated with memantine benefited from a significant delay of clinical worsening compared with placebo-treated patients, and fewer patients faced clinical worsening in the relevant domains cognition (24.6% vs 36.2%, p < 0.001), activities of daily living (56.2% vs 61.6%, p < 0.05) and global impression of change (40.9% vs 49.8, p < 0.001). In addition, response to treatment on the combined domains (triple response) was significantly in favour of memantine compared with placebo, with fewer patients showing clinical worsening (11.0% vs 20.4%, p < 0.001). CONCLUSIONS: 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.

Measuring therapeutic efficacy in patients with Alzheimer's disease: role of instruments.

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.