Comparative Effectiveness of Second Generation Long-acting Injectable Antipsychotics Based on Nationwide Database Research in Hungary: An Update.

Greater 1-year and 2-year treatment continuation rates and longer median time to discontinuation for second-generation antipsychotic (SGA) long-acting injectables (LAIs) vs oral antipsychotics (OAPs) in Hungary were previously reported. This study reports an updated comparison between new LAIs vs OAPs in Hungary. De-identified claims data from Hungarian National Health Insurance Fund database of schizophrenia patients who were newly initiated on SGAs (November 01, 2016 to June 30, 2017) were retrospectively analyzed. Primary outcomes were likelihood of all-cause 1-year and 1.5-year discontinuation of newly initiated SGA and median time till discontinuation. Among 5400 patients, 3977 (73.6%) were OAP users and 1423 (26.4%) were LAI users. The 1-year continuation rate were 12.7% (risperidone)-34.1% (olanzapine) for OAPs and 26.4% (risperidone LAI)-78.6% (paliperidone 3-monthly [PP3M]) for LAIs. The 1.5-year continuation rates were 9.3%-29.5% for OAPs and 24.9%-76.4% for LAIs. Median (95% CI) time to discontinuation was 52 (33-67) days (clozapine)-152 (134-168) days (aripiprazole) for OAPs and 125 (64-196) days (risperidone LAI)-491 (250-not reached) days (aripiprazole LAI) for LAIs. All-cause discontinuation risk was significantly higher in all OAPs vs PP3M and aripiprazole LAI (P < .01) as well as in each LAI vs PP3M (P < .05). Patients switching on new LAIs from another LAI remained longer than those who switched from OAPs/no previous treatment. Results showed the advantage of LAIs over OAPs in terms of time to treatment discontinuation. Moreover, new SGA LAIs (PP3M) seem to be better than previous LAIs in terms of time to treatment discontinuation.

Clinical characteristics of treatment-resistant depression in adults in Hungary: Real-world evidence from a 7-year-long retrospective data analysis.

PURPOSE: Treatment-resistant depression (TRD) is associated with a poor quality of life and high economic burden. This observational retrospective epidemiological study aimed to estimate the proportion of patients with TRD within a cohort of patients with major depressive disorder (MDD) in Hungary and examine the mortality and comorbidities of patients with and without TRD. PATIENTS AND METHODS: This study included patients with MDD who experienced onset of a new depressive episode between 01 January 2009 and 31 August 2015, using data from a nationwide, longitudinal database. RESULTS: Overall, 99,531 patients were included in the MDD cohort, of which 8,268 (8.3%) also met the criteria for TRD. The overall survival of non-TRD patients was longer than in TRD patients; the risk of mortality for TRD patients was significantly higher than of non-TRD patients (HR [CI] 1.381 [1.212-1.571]; p<0.001). Patients with TRD had a significantly higher probability of having "Neurotic, stress-related and somatoform disordersË®, autoimmune conditions, cardio- or cerebrovascular diseases, thyroid gland diseases and self-harming behaviour not resulting in death than non-TRD patients (for all comparisons, p values were less than 0.005). DISCUSSION: To our best knowledge, this is the first study to assess the frequency of TRD in Hungary. In a cohort of Hungarian MDD patients, we have found that the proportion of TRD (~8.3%) is comparable to those reported in previous studies with similar methodology from other countries. The majority of our other main findings (e.g. more frequent self-harming behaviour, increased risk of "Neurotic, stress-related and somatoform disordersË® and higher overall mortality in TRD subjects) are also in line with previous results from other countries. Taking the substantial proportion of patients with TRD into consideration, a more comprehensive and targeted treatment strategy would be required for these individuals.

[Become the expert and embrace a positive attitude: communication strategies for discussing long-acting injectable antipsychotic treatment with patients living with schizophrenia].

Patients with schizophrenia often experience relapses that negatively impact long-term outcomes. Continuous antipsychotic treatment can reduce relapse risk; however, this can be hindered by nonadherence resulting from the poor insight, which is often associated with schizophrenia. A strong patient-physician-carer alliance can improve patient insight, and adherence. Long-acting injectable antipsychotic treatment (LAT) provides continuous treatment; however, its acceptance by the patient is often compromised by a lack of physician-patient communication. The COMP approach (Connectedness, Openness, Motivation, Partnership) was developed to build effective communication and aid discussions around treatment. Insights on COMP fed into the development of COMPLETE - a tool for discussing LAT with eligible patients including the following components: 'Life goals', 'Establish connection between goals and therapy', 'Therapy introduction' and 'Encourage long-term motivation'. The overarching objective of COMPLETE is to improve long-term outcomes in patients with schizophrenia. This article discusses the development of COMPLETE and its potential use in the management of schizophrenia.

[Patient Journey in Schizophrenia - Lessons of a Hungarian Survey].

The disorder-related experiences of schizophrenic patients are an important basis for personalized treatment. This illness experience is now described with the concept of patient journey. The patient journey shows how the symptoms and treatment interfere with the patient's personal existence and how they affect the optimal functionality. The purpose of our research was to map the patient journey in Hungary, among patients with schizophrenia, in particular how they represent their illness, what kind of met and unmet needs they have in relation to living with the disorder or their treatment. 155 patients living with schizophrenia participated in the study. The survey was conducted through self-completed questionnaires covering the following topics: first encounter with the disorder, life with the disorder, treatment expectations, experiences, support and needs. The first encounter of the patients with the disease was predominantly traumatizing, and the refusal of the diagnosis was characteristic. The inappropriate information on the disorder and the treatment might have been also responsible for this negative perception. Nevertheless, patients were expecting the information primarily from the treatment staff. The decisive majority expects from treatment the possibility of a normal life, the maintenance of stability, and according to every second patient well-being is also a basic requirement. Three-quarters of the patients think that effective medication and treatment staff are the greatest help in relation to the disorder. A significant proportion of the patients formulated the need for psychic and family support, and the need for social relations. Patients with schizophrenia have significant difficulties with financial problems, medication side effects, and stigma. Our results confirm that the subjective perception of patient journey of patients with schizophrenia is significantly determined by the met and unmet needs. The results also emphasize the importance of adequate information transfer and the therapeutic relationship.

Treatment adherence and insight in schizophrenia.

BACKGROUND: Lack of adherence to treatment in patients with schizophrenia is a major risk factor for poor outcome, including relapse, rehospitalization, and suicide. Poor insight into illness may be a leading cause for partial- or nonadherence since a high proportion of patients with schizophrenia are partially or completely unaware of their mental disorder. OBJECTIVE: The primary objective was to estimate the impact of lack of insight on adherence to medication based on a population of patients in Hungary who had the diagnosis of schizophrenia. The secondary objective was to investigate the association of the different aspects of insight (awareness of illness, the capacity to relabel psychotic experiences as abnormal, treatment acceptance) with (1) recent adherence behavior; (2) current mental state; (3) remission/non-remission status as measured by remission severity criteria; and (4) demographic and treatment history data. METHOD: This was cross-sectional, noninterventional study, carried out under daily clinical practice conditions, with no influence exerted upon clinical practice in view of the observational nature of the study. Eligibility criteria included: a) patients' age (>18 years), b) diagnosis of schizophrenia (ICD-10), c) signed informed consent, d) no concomitant participation in another clinical trial. Study sites represented Mental Health Centers and outpatient clinics of hospital psychiatric units. Each investigator was asked to enroll patients consecutively. The final analysis sample comprised 262 patients, distributed across 13 sites. The following data were collected: general sociodemographic and clinical data (age, sex, level of education, socioeconomic situation, family support, psychiatric diagnosis, years of evolution, pharmacological and/or psychosocial treatments at the time of inclusion in the study, previous psychiatric admissions), with assessments of the Schedule of Assessing components of Insight (SAI), Compliance Rating Scale (CRS), Clinical Global Impression Scale (CGI-S), Remission Severity Criteria. RESULTS: Patients enrolled in the study had a mean (SD) age of 43.0 (12.6) years, with a 12.3 (3.0) years of education, and approximately evenly balanced gender distribution. According to the clinical judgment of the treating physicians, 29.1% of the patients were not taking their prescribed antipsychotic medication in our target population. The primary logistic regression analysis indicated a significant relationship between the total score on the SAI scale and the Compliance Scale (Spearman correlation=0.58; p<0.0001). The relationship was significant for each of the three subscales of SAI. Secondary analyses showed a significant negative association between compliance and score on the CGI-S scale (Spearman correlation: -0.54; p<0.0001), and compliance and hostility, as measured by the PANSS hostility item (Spearman correlation: -0.40; p<0.0001). We found no significant relationship between compliance and age, gender or education years (p>0.1 in all cases). CONCLUSIONS: The results of the present study support the hypothesis that the level of insight and compliance are strongly associated, and that more severe symptoms and increasing levels of hostility, in particular, markedly reduce the compliance of the patients with schizophrenia. Capturing different aspects of insight may be helpful in understanding and improving adherence behavior in clinical practice.

Comparative effectiveness of depot and oral second generation antipsychotic drugs in schizophrenia: a nationwide study in Hungary.

We conducted a nationwide, full-population based investigation to evaluate the comparative effectiveness of all marketed second generation antipsychotic drugs (SGA) prescribed for outpatients with the diagnosis of schizophrenia in Hungary. Using the national central register, our observational follow-up study included all patients with schizophrenia or related disorder between 01/01/2006 and 30/06/2008. The study cohort comprised 9567 patients who started new SGA during the inclusion period (01/07/2007-30/06/2008). All-cause medication discontinuation of 8 SGAs (1 depot and 7 oral formulations) marketed during the inclusion period, and the time to all-cause discontinuation were the main outcomes. Statistical models included the Kaplan-Meier and the Cox proportional hazards models with propensity score adjustment. Patients treated with a depot formulation risperidone had the longest time to discontinuation with a median of 215 days (95%CI:181-242 days), which was statistically significantly different compared to patients treated with the rest of the medications: olanzapine (136 days, 95%CI:121-153 days), aripiprazole (102 days, 95%CI:81-126 days), ziprasidone (93 days, 95%CI:82-119 days), quetiapine (89 days, 95%CI:81-100 days), clozapine (76 days, 95%CI:54-92 days), amisulpride (73 days, 95%CI:62-85 days), and risperidone (55 days, 95%CI: 41-63 days). Our results in Hungary are partly similar to those of a recent register-based study in Finland with patients who were discharged from their first hospitalization for schizophrenia (Tiihonen et al., 2006, 2011); namely the median times to all-cause medication discontinuation were <120 days for the majority of the oral SGA. In terms of medication differences, our data support the superior effectiveness of the depot formulation regarding all-cause discontinuation, followed by olanzapine at the efficacy rank order.

Parallel expression of alphaIIbbeta3 and alphavbeta3 integrins in human melanoma cells upregulates bFGF expression and promotes their angiogenic phenotype.

Previous studies indicated that transfection of the platelet integrin alphaIIbbeta3 into human melanoma cells expressing integrin alphavbeta3 promoted their in vivo (but not in vitro) growth and cell survival. To reveal the underlying pathomechanism, we have analyzed the angiogenic phenotype of alphaIIbbeta3 integrin-transduced human melanoma cells expressing integrin alphavbeta3. Upon heterotopic or orthotopic (intracutaneous) injections into SCID mice, the alphaIIbbeta3 integrin-overexpressing clones, ESL, ESH, 19L and 19H, grew more rapidly than the mock transfectant (alphavbeta3 expressing) clone, 3.1P. Morphometry demonstrated an increased intratumoral microvessel density in 19L and 19H tumors compared to 3.1P. Immunocytochemistry and flow cytometry indicated that vascular endothelial growth factor (VEGF) is constitutively expressed in the majority of the cells of both the mock and the alphaIIbbeta3 integrin-transfected clones. However, the mock transfectant clone, 3.1P, did not express basic fibroblast growth factor (bFGF) at protein level (<1%), unlike the alphaIIbbeta3 integrin-transfected clones, 19L and 19H, (33.9 and 84.1%, respectively). Quantitative PCR analysis of 6 related human melanoma clones with various levels of alphaIIbbeta3 integrin expressions revealed a correlation between the alphaIIb protein and bFGF mRNA expressions. Furthermore, cDNA microarray analysis of the 19H cells revealed 12 downregulated and 36 upregulated genes [among them 3 upregulated vasculogenic mimicry-genes (CD34, endothelin receptor B, Prostaglandin I-2 synthase)] when compared to 3.1P cells. The altered bFGF expression may be influenced by integrin-linked signaling, since bbeta3-endonexin is upregulated in alphaIIbbeta3-transfected cells and tyrosine kinase inhibitors downregulate bFGF both at mRNA and protein levels. We propose here that the illegitimate expression of alphaIIbbeta3 integrin in human melanoma cells already expressing alphavbeta3 integrin may alter their in vivo growth properties due to the modulation of their angiogenic phenotype.

[Pharmacoeconomic review of the use of injectable long-acting risperidone]. / A tartós hatású risperidon injekció alkalmazásának farmakoökonómiai vonatkozásai.

Schizophrenia is a severe and chronic illness as well as one of the most expensive illnesses to treat. Relapse and rehospitalisation contributes significantly to the economic burden of schizophrenia. Partial compliance with antipsychotic medication was associated with an increased risk of inpatient hospitalization. Health care resource use is significantly reduced in patients with stable schizophrenia or schizoaffective disorder receiving long-acting, injectable risperidone. It is highly likely that these reductions will decrease healthcare costs in patients receiving long-acting risperidone. In this article cost-effectiveness models of long-acting risperidone developed for different countries are discussed. Long-acting risperidone produced additional clinical benefit and cost savings compared with other treatment strategies, despite significant variations in cost-effectiveness. One factor remained valid for each country: improved adherence arising through the use of long-acting risperidone provides a cost-effective strategy for treating patients with schizophrenia. On the basis of the cost-effectiveness evaluations in different countries long-acting risperidone seems to offer a cost saving treatment option for patient with schizophrenia under Hungarian circumstances. Further assessment of these models in a pragmatic study and actual monitoring of health care resource utilization should confirm the above assumption.

[Experience with Risperidone in the treatment of institutionalized mentally retarded patients, with special reference to treatment of aggressive states]. / Risperidonnal szerzett tapasztalataink mentálisan retardált betegeket ellátó szakotthonban, különös tekintettel az agresszív állapotok kezelésére.

Aggression has become a problem of our everyday life; every psychiatrist meets aggressive patients in his practice almost daily. Aggression represents a special problem in the case of institutionalized, mentally retarded (severe and moderate) patients, when it is associated with agitation, deficit of critical functions, impulsiveness, mood disorders. The nursing staff of these institutions is often overworked; the affective outbursts and aggressive behavior of mentally retarded patients may provoke a hostile attitude on the part of the nursing staff towards the patients. In the case of mentally retarded patients, unpredictable events may occur at any time. The structural background of mental retardation, the function of the affected cerebral structures, is not completely clarified. It was found in several studies that risperidone is effective in the treatment of agitation and aggressive behavior; the incidence of side effects is much lower than in the case of typical antipsychotics. We started the treatment with risperidone of 60 mentally retarded patients; we evaluated the therapeutic outcome after a three-month follow-up period using a rating scale made specially for this purpose. An attempt was made to compare the therapeutic results obtained in the risperidone group with the condition of patients receiving typical antipsychotics. It was found that, in the case of several items (aggression, agitation, deficit of critical functions, mood disorders, sleep disturbances, involvement in therapeutic activities), risperidone was significantly more effective than typical antipsychotics, and the incidence of extrapyramidal symptoms and other adverse events was much lower. It was hardly necessary to impose restraints in the risperidone group. In the care of mentally retarded patients, the use of risperidone has many long-term advantages, and hence it represents an effective alternative to typical antipsychotics.