Veröffentlichung von Ergebnissen aus abgeschlossenen nicht-interventionellen Studien (NIS) im VFA-Studienregister:

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1 Veröffentlichung von Ergebnissen aus abgeschlossenen nicht-interventionellen Studien (NIS) im VFA-Studienregister: NIS Grunddaten: Studientitel: InORS - International Observational Registry on Schizophrenia Zielsetzung / Fragestellung: The primary objective was to prospectively assess medication usage patterns under routine clinical practice, related to initiation of treatment with Risperdal CONSTA, hereafter referred to as Consta, (gluteal or deltoid injections; 25, 37.5, and 50 mg every 2 weeks) and oral antipsychotic treatments in subjects with schizophrenia in a naturalistic setting. Additional objectives of the study were: 1. To collect 6-month retrospective and 1-year prospective data to allow the exploration of treatment outcomes including hospitalizations and rehospitalizations, with Consta and oral antipsychotics, in relation to previous treatments. 2. To evaluate reasons for initiation and/or discontinuation of new antipsychotic medications, including subject satisfaction with treatment. 3. To explore relevant factors for subject adherence to treatment. 4. To document clinical effectiveness and functionality of subjects on Consta and oral antipsychotics in daily clinical practice (as measured by the Global Assessment of Functioning [GAF] scale). Additionally, the long-term safety of Consta and oral antipsychotics was assessed. Handelsname: Risperdal CONSTA Studiennummer: RISSCH4230 NIS Abschlussdaten: Methodologie: This was an observational, non-interventional registry designed to assess medication usage patterns and to collect, in routine clinical practice, long-term outcomes and relevant factors for subject adherence to treatment in subjects receiving antipsychotic treatment with Consta or oral antipsychotics. Six-month retrospective data and 12-month prospective data were collected. An interim statistical analysis was performed when 600 subjects had completed the interim period of 3 months. The interim analysis consisted of a limited exploratory statistical analysis of effectiveness and safety data for 613 subjects. Analysierte Anzahl der Patienten: 1084 Diagnose und Selektionskriterien: This was a non-interventional study, with treatment decisions made prior to selection of subjects, and minimal selection criteria were applied. To be eligible for documentation, subjects had to be at least 18 years old, have a diagnosis of schizophrenia with at least 6 months of retrospective clinical records, and be newly EG, JMO/Februar 2011 Seite 1 von 8

2 initiated or switched to Consta or an oral antipsychotic not longer than 2 weeks previously. Subjects with established treatment-refractory schizophrenia or with a history of neuroleptic malignant syndrome were not eligible for documentation in the study. Dauer: 03 June March 2012 Stand der Information: Schizophrenia is a chronic, severe and disabling mental disorder. It is characterized by a variety of clinical manifestations, including positive and negative symptoms, lack of insight, cognitive impairment, and social and occupational disfunctioning 1. The lifetime prevalence of schizophrenia has been estimated to be up to 1%, although rates vary significantly across geographic regions and cultures 2. Schizophrenia has a large social and economic impact on the subjects, their families, friends, and the community. The economic burden is disproportionately high as it accounts for between 1.5% and 3% of healthcare costs 3. Hospitalization for schizophrenia is a large contributor to the burden on healthcare systems, whereas medication costs only contribute a small proportion to overall costs 4. Schizophrenia typically requires long-term or even life-long treatment. The treatment goal is to control symptoms (positive and negative), prevent recurrence of psychotic episodes, improve quality of life (physical, psychological, and social) and facilitate social and vocational reintegration. Pharmacological therapy is the main approach to the treatment of schizophrenia. While atypical antipsychotic medications offer particular advantages over typical antipsychotic drugs, there is room for further benefit from new treatment options as indicated in recent studies 5,6. Compliance relates to the extent to which patients behavior corresponds with advice given by their physicians. As compliance is not an all or nothing phenomenon, patients are often partially compliant. These patients have accepted their diagnosis and requirement for treatment, however, they do not receive the maximum benefit from their treatment regimen and, therefore, may appear to be non-responsive or only partially responsive to their antipsychotic therapy 7. Approximately 40% of patients with schizophrenia are poorly compliant to their antipsychotics at any given time. However, little is known about patients compliance over time, although this has important implications for services. The results of a 4-year study examining antipsychotic compliance in patients with schizophrenia showed that antipsychotic compliance is not a stable trait 8. Factors that influence compliance rates are not negligible. They often overlap or influence each other, and fall into 4 main categories: patient-, treatment-, environment-, and physician-related 9. Patient-related factors can be defined as a multidimensional concept including lack of insight, the degree of psychic self-perception, the awareness of the illness and symptoms 10, attribution of symptoms to the illness, the awareness of the social consequences of the disease and the necessity of a treatment 11, negative symptoms (such as apathy 12 ), cognitive impairment, attentional and memory deficits 13,14, and co-morbid substance abuse 15. Treatment-related factors consist of adverse effects associated with antipsychotic drugs. The extent of efficacy can also determine compliance. If a treatment is not as effective as patients expect it to be, they may simply stop taking it 16. Conversely, if patients achieve symptom relief or remission, they may stop taking their medication believing that it is not longer necessary 12. The environment in which patients live can have a significant impact on their compliance, with negative attitudes of relatives or partners adversely affecting compliance with medication9. Living alone is also associated with poor compliance 17. Conversely, the availability of relatives to support and assist or supervise medication is an important factor in enhancing compliance 12,18. The therapeutic alliance between patients and healthcare professionals has also an important influence on compliance 18,19. Patients need to feel involved in making the decisions about their treatment and feel that their treatment team is interested in them and will listen to their concerns regarding medication, including side effects 12. EG, JMO/Februar 2011 Seite 2 von 8

3 There are a number of advantages to long-acting injectable medications that have not been fully considered. The major advantage of administering this kind of antipsychotics is the promotion of compliance 20. Although they cannot eliminate non-compliance, they do prevent covert non-compliance 21 since non-compliance with long-acting injectable agents can be immediately identified 22. Thus, compliance failure can be differentiated from efficacy failure in patients treated with long-acting injectable agents, thereby reducing the use of rescue medications and the need for switching to a second-choice antipsychotic7. The majority of evidence indicates that long-acting injectable medications can increase compliance and reduce relapse rates 23,24. Furthermore, treatment guidelines recommend the use of long-acting injectable medications for patients who are suspected of non-compliance with oral medication 25. The first long-acting injectable preparation of an atypical antipsychotic, i.e., risperidone, is designed for intramuscular administration every 2 weeks. In contrast to the long-acting injectable conventional antipsychotics, which are oil-based preparations and often cause injection site pain and reactions, the aqueous suspension of risperidone eliminates some of the pain associated with oil-based injections 7. Longacting risperidone may therefore combine the benefits of atypical antipsychotics with the long-acting injection delivery system required to build a platform for improved outcomes 9. Long-acting risperidone has been the first atypical antipsychotic that ensures medication delivery in patients who are partially compliant and therefore significantly decreases the risk of relapse and rehospitalization, achieving long-term stability due to its 2-weekly medication administration9, Recently, the results of a 2-year, prospective, observational study of patients with schizophrenia, designed to evaluate long-term treatment outcomes in routine clinical practice (e-star electronic Schizophrenia Treatment Adherence Registry) were published. It was shown that, compared to oral antipsychotic drugs, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospitalization, as well as a decrease in the number of days in hospital. Improved treatment adherence, increased efficacy, and reduced hospitalization with RLAI may offer the opportunity for substantial therapeutic improvement in schizophrenia in routine clinical practice 30. Nevertheless, this study did not collect information from other treatment strategies (oral antipsychotic drugs) in most of the countries in which it was conducted and it does not include information from different injection sites. When the choice was given to patients, a review of 6 studies demonstrated that patients expressed a preference for long-acting injectable medication in 5 of the studies. In the 6th study, the preference for an oral agent was specifically the atypical antipsychotic risperidone over conventional depot medication 31. Despite its proven efficacy and tolerability, the acceptance of long-acting injectable antipsychotics, by patients with schizophrenia and physicians, is still limited. Results of a survey among physicians and nurses from around Europe, reveal that the choice of the injection site for administration of long-acting antipsychotics into the gluteal or deltoid muscle also plays an important role. Patients preferred injections in the deltoid muscle as it reduces social embarrassment, it is less intrusive, and is perceived as more respectful 37. The availability of an alternative injection site (i.e., deltoid muscle) could overcome some of the reluctance to RLAI in the long-term treatment of schizophrenia. Pharmacological studies on the deltoid injection site have successfully been performed The results of these studies showed that deltoid and gluteal injections are bioequivalent with respect to peak and total plasma exposure in the dose range of 12.5 to 50 mg RLAI, and that they exhibit dose-proportional pharmacokinetics independent of the injection site (i.e., deltoid or gluteal). Eight-week tolerability results of the deltoid injection site revealed drop-out rates due to lack of tolerability of about 4%. Up till now, the intramuscular administration route for RLAI, and other long-acting injectables, was only approved for gluteal injection (2 ml diluent every 2 weeks). The deltoid formulation, including the 2-mL diluents, proposed for administration in the deltoid muscle using a 1-inch needle is identical to the formulation for injection into the gluteal muscle (using a 2-inch needle). During the conduct of this study, the deltoid injection site has become an approved alternative and information from subjects who could receive injections in this muscle will be also documented for this study. EG, JMO/Februar 2011 Seite 3 von 8

4 References: 1. Diagnostic and Statistical Manual of Mental Disorders, 4th. Edition (DSM-IV). 2. Johannessen JO. Review: lifetime prevalence of schizophrenia and related disorders is about 5.5 per 1000 but there is significant variation between regions. Evid Based Ment Health 2003; 6(3):74 3. Knapp M. Schizophrenia costs and treatment cost-effectiveness. Acta Psychiatr Scand Suppl 2000; (407): Knapp M, Chisholm D, Leese M et al. Comparing patterns and costs of schizophrenia care in five European countries: The EPSILON study. European psychiatric services: Inputs linked to outcome domains and needs. Acta Psychiatr Scand 2002; 105(1): Lieberman JA, Stroup TS, McEvoy JP et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New Engl J Med 2005; 353(12): Jones PB, Barnes TR, Davies L et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost utility of the latest antipsychotic drugs in schizophrenia study (CUtLASS 1). Arch Gen Psychiatry 2006; 63(10): Keith SJ & Kane LM. Partial compliance and patient consequences in schizophrenia: our patients can do better. J Clin Psychiatry 2003; 64(11): Valenstein M, Ganoczy D, McCarthy JF et al. Antipsychotic adherence over time among patients receiving treatment for schizophrenia: a retrospective review. J Clin Psychiatry 2006; 67(10): Llorca PM. Partial compliance in schizophrenia and the impact on patient outcomes. Psychiatry Res 2008; 161(2): Aguglia E, De Vanna M, Onor ML et al. Insight in persons with schizophrenia: effects of switching from conventional neuroleptics to atypical antipsychotics. Prog Neuropsycopharmacol Biol Psychiatry 2002; 26(7-8): Dam J. Insight in schizophrenia: a review. Nord J Psychiatry 2006; 60(2): Oehl M, Hummer M, Fleischlacker WW. Compliance with antipsychotic treatment. Acta Psychiatr Scand Suppl 2000; (407): Donohoe G, Owens N, O Donnell C et al. Predictors of compliance with neuroleptic medication among inpatients with schizophrenia: a discriminant function analysis. Eur Psychiatry 2001; 16(5): Prouteau A, Verdoux H, Briand C et al. Cognitive predictors of psychosocial functioning outcome in schizophrenia: a follow-up study of subjects participating in a rehabilitation program. Schizophr Res 2005; 77(2-3): Owen RR, Fischer EP, Booth BM et al. Medication noncompliance and substance abuse among patients with schizophrenia. Psychiatr Serv 1996; 47(8): Liu-Seifert H, Adams DH, Kinon BJ. Discontinuation of treatment of schizophrenic patients is driven by poor symptom response: a pooled post-hoc analysis of four atypical antipsychotic drugs. BMC Med 2005; 3: Olfson M, Mechanic D, Hansell S et al. Predicting medication noncompliance after hospital discharge among patients with schizophrenia. Psychiatr Serv 2000; 51(2): Löffler W, Kilian R, Toumi M et al. Schizophrenic patients subjective reasons for compliance and noncompliance with neuroleptic treatment. Pharmacopsychiatry 2003; 36(3): Rittmannsberger H, Pachinger T, Keppelmüller P et al. Medication adherence among psychotic patients before admission to inpatient treatment. Psychiatr Serv 2004; 55(2): Gerlach J. Oral versus depot administration of neuroleptics in relapse prevention. Acta Psychiatr Scand Suppl 1994; 382: Valenstein M, Copeland LA, Owen R et al. Adherence assessments and the use of depot antipsychotics in patients with schizophrenia. J Clin Psychiatry 2001; 62(7): EG, JMO/Februar 2011 Seite 4 von 8

5 22. Quraishi S & David A. Depot pipothiazine palmitate and undecylenate for schizophrenia (Cochrane Review). Cochrane Database Syst Rev 2001; (3): CD Davis JM, Kane JM, Marder SR et al. Dose response of prophylactic antipsychotics. J Clin Psychiatry 1993; 54 (suppl): Davis J, Metalon L, Watanabe M et al. Depot antipsychotic drugs: Place in therapy. Drugs 1994; 47(5): American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry 1997; 154 (suppl 4): Kane JM, Eerdekens M, Lindenmayer JP et al. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry 2003; 160(6): Fleischhacker WW, Oehl MA, Hummer M. Factors influencing compliance in schizophrenia patients. J Clin Psychiatry 2003; 64 (suppl 16): Fleischhacker WW, Eerdekens M, Karcher K et al. Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic. J Clin Psychiatry 2003; 64(10): Chue P, Llorca P, Duschesne I et al. Hospitalization rates in patients during long-term treatment with long-acting risperidone injection. J Applied Res 2005; 5(2): Olivares JM, Rodriguez-Morales A, Diels J et al. Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: Results from the electronic Schizophrenia Treatment Adherence Registry (e-star). Eur Psychiatry 2009, doi: /j.eurpsy Walburn J, Gray R, Gournay K et al. Systematic review of patient and nurse attitudes to depot antipsychotic medication. Br J Psychiatry 2001; 179: Schizophrenia: Core interventions in the treatment and management of schizophrenia in adults in primary and secondary care (update). National clinical practice guideline number X. National collaborating centre for mental health commissioned by the National Institute for Health and Clinical Excellence. Update of NICE Clinical Guideline 1, published in December Hofer A, Hummer M, Huber R et al. Selection bias in clinical trials with antipsychotics. J Clin Psychopharmacol 2000; 20: Robinson D, Woerner MG, Pollack S et al. Subject selection biases in clinical trials: data from a multicenter schizophrenia treatment study. J Clin Psychopharmacol 1996; 16: Thornly B, Adams C. Content and quality of 2000 controlled trials in schizophrenia over 50 years. Br Med J 1998; 317: Black N. Why we need observational studies to evaluate the effectiveness of health care. Br Med J 1996; 312: Geerts P, Bloem S, Van Bulck A. Deltoid administration of long-acting antipsychotics: physician and nurse attitudes. Poster; 14th World Congress of Psychiatry (WCP) of Kriterien der Bewertung analog ICH E3: Wirksamkeit unter Alltagsbedingungen: At the start of the documentation, subject characteristics and retrospective 6-month treatment history were recorded. During the 12-month prospective period, treatment outcomes were evaluated using clinicianadministered assessments. Assessments were conducted at baseline and at Months 1, 3, 6, 9, and 12. Psychiatric hospitalizations were recorded for both the retrospective and prospective periods to assess the outcomes of medication strategies. Details of the newly-initiated Consta or oral antipsychotic treatment and concomitant use of other antipsychotic treatment were also documented. Any switch in the subject s antipsychotic treatment since the last assessment was recorded at each visit. Reasons for initiating and discontinuing antipsychotic treatment were collected from the clinical records. Concomitant use of EG, JMO/Februar 2011 Seite 5 von 8

6 anticholinergics, antidepressants, mood stabilizers, benzodiazepines, sedatives, anxiolytics, and somatic medication was also recorded. The Clinical Global Impression - Schizophrenia (CGI-SCH) scale was used to evaluate severity and treatment response and the GAF scale was used to rate subjects' overall level of functioning. The subjects' satisfaction with the antipsychotic treatment was evaluated using the Medication Satisfaction Questionnaire (MSQ), a single-item global subject-rated scale. Adherence to treatment was recorded using the 7-point observer-rated Compliance Rating Scale (CRS). Sicherheit: Safety evaluations included adverse event (AE) data, injection site pain scores, and body weight. Andere: Nicht zutreffend Statistische Methoden analog ICH E3: Methoden: The sample size calculation indicated that a sample size of 128 subjects was required to investigate maintained effectiveness using the CGI-SCH parameter in a single group. Assuming that a change of 0.4 points versus baseline on CGI-SCH is a minimum clinically relevant difference, a standard deviation of 1.6 and a one-sided significance level of would have 80% power to test equivalence. Hence, it was estimated that a total of approximately 1200 subjects would be sufficient to construct at least 6 to 10 clinically relevant subgroups of subjects and to enable separate analysis of these subgroups. Baseline was defined as the day of initiation of the Consta or oral antipsychotic treatment, which defined entry into the study. All subjects were analyzed by the antipsychotic medication that subjects were taking at the onset of the study (ie, their baseline medication). Subjects were grouped into baseline Consta or baseline Oral therapy groups. The period of observation began at the start of the study and continued until the end of Consta/oral therapy. The baseline oral antipsychotic therapy period ended if a subject changed medication (molecule), even if the new medication was an oral antipsychotic medication. Subjects who received Consta at the onset of the study were further analyzed by grouping by injection site. Subjects who received Consta by gluteal injection at the start of the study were analyzed as the baseline Consta-Gluteal group. Subjects who received Consta by deltoid injection at the start of the study were analyzed as the baseline Consta-Deltoid group. For the Medication Switch Pattern I (C:O pattern) analysis, medication periods were categorized as either C- (Consta) or O- (NonConsta) periods. C-periods were defined as periods during which the subjects received Consta therapy, regardless of injection site (gluteal or deltoid). Since supplemental oral antipsychotic medication should be given during the first 21 days of Consta therapy, the first 28 days of Consta plus supplemental oral therapy were considered as a C period. O periods were defined as periods during which subjects received single or multiple therapies including oral antipsychotic or depot medication but not Consta. Medications started prior to the prospective period were considered concomitant medications, and therefore were not considered to be part of the study medication. The definition of medication switches included addition or deletion of antipsychotic medication after baseline, changes to another antipsychotic medication within the same class, or stopping an antipsychotic medication while another medication was ongoing. If a subject switched his/her medication across the C- or O- category after baseline, the series of medication category was created to define the medication switch pattern. Hence, potential observable treatment patterns by the end of the 12 month study period included, but were not limited to: C; O; C-O; O-C; C-O-C; O-C-O, etc. Discontinuation of antipsychotic treatment did not result in discontinuation from the study. Therefore, any subject who discontinued antipsychotic treatment before the end of the prospective period was analyzed according to the medication switch pattern up to the point of stopping treatment. Additionally, a medication category (II) analysis was used to examine switches between antipsychotic monotherapy and polytherapy. EG, JMO/Februar 2011 Seite 6 von 8

7 Zusammenfassung analog ICH E3: Ergebnisse zur Wirksamkeit unter Alltagsbedingungen: Over the course of the baseline Consta treatment period, duration per stay, total length of stay, and proportion of hospitalized days data all indicated reduced hospitalization time during the prospective period compared with the retrospective period. In contrast, for subjects in the baseline Oral medication group, these data were similar before and during the prospective period. Medication satisfaction (MSQ) and adherence to treatment (CRS) improved significantly over the course of the baseline treatment period for both the Consta and Oral groups (p<0.001). However the observed improvements were greater in the Consta group than in the Oral group for both medication satisfaction (p=0.013) and adherence to treatment (p<0.001). The Consta-Gluteal and -Deltoid subgroups were comparable in terms of medication satisfaction and treatment adherence scores. Reductions in symptom severity were demonstrated by significant decreases in CGI-SCH scores at the end of the baseline treatment period for both the baseline Consta and Oral treatment groups (p<0.001). The CGI- SCH scores for overall severity showed greatest decreases in the baseline Consta group (p=0.004). GAF scores demonstrated improved functioning after the baseline treatment period for both Consta and oral antipsychotic medications (p<0.001). However, this improvement was significantly greater for the Consta group than in the Oral group (p<0.001). Greatest evidence of effectiveness of treatment was seen in subjects remaining on Consta (C-) or NonConsta (O-) therapy during the prospective period. In particular, C-pattern subjects showed marked improvements in functioning rated by GAF scores. In contrast, treatment outcomes were consistently less favorable for subjects with more complex medication switch patterns. The percentages of subjects who clinically deteriorated during the prospective period were substantially higher in the C-O (24.6%) and 'Other' (35.2%) pattern groups than among C- (8.2%) or O- (11.0%) pattern groups. Overall, subjects in the C-O and 'Other' categories demonstrated smaller decreases in CGI-SCH symptom severity and less improvement in functioning compared with the other treatment patterns. Benzodiazepine/sedative/anxiolytic use was highest in the C-O (41.9%) and 'Other' (55.6%) groups. Ergebnisse zur Sicherheit: Weight increased (7.2%), psychotic disorder (5.1%), schizophrenia (4.2%), anxiety (3.2%), insomnia (2.3%), and extrapyramidal disorder (2.2%) were the only individual AE preferred terms reported in more than 2% of all subjects during the 12-month prospective period. Weight increased, insomnia, anxiety, psychotic disorder, and somnolence were the only individual preferred terms reported in more than 2% subjects in the baseline Consta or baseline Oral treatment groups. Evaluation of AEs by Medication Switch pattern I (C:O pattern) revealed a higher incidence of AEs in the NonConsta (O-) group than in the Consta (C-) group. This may be related to differences in effectiveness, or to exposure to more medications in the O-group. However, the more complex treatment patterns (C-O and 'Other' patterns) were associated with highest relative frequencies of AEs, severe AEs, serious AEs (SAEs) and AEs requiring discontinuation of antipsychotic treatment, as shown in the table below. This may reflect a lack of effectiveness of treatment in these subjects. Frequency of AEs, Severe AEs, SAEs and AEs Requiring Treatment Discontinuation by Medication Switch Pattern I (C:O Pattern) Number of Subjects With: O (n=490) C (n=426) C-O (n=105) Other (n=63) 1 AE 214 (43.7%) 132 (31.0%) 67 (63.8%) 44 (69.8%) 1 Severe AE 34 (6.9%) 20 (4.7%) 18 (17.1%) 13 (20.6%) 1 SAE 66 (13.5%) 43 (10.1%) 32 (30.5%) 27 (42.9%) Treatment stopped a due to AE 47 (9.6%) 13 (3.1%) 29 (27.6%) 8 (12.7%) a Permanent stop of antipsychotic treatment In total, 11 deaths occurred during the prospective period. Prior to death, 6 subjects had received Consta (2 of whom were also receiving oral antipsychotic treatments), 4 subjects had received oral antipsychotic medication, and 1 subject had discontinued antipsychotic treatment several months before death. Completed suicide (6 subjects) was the most common cause of death. Only the death of 1 subject who committed suicide whilst receiving Consta, oral flupentixol and oral ziprasidone was described as possibly related to antipsychotic medication. EG, JMO/Februar 2011 Seite 7 von 8

8 Injection site pain, scored according to a 10 point scale, indicated a low absolute level of pain for both gluteal and deltoid Consta administration sites. However, the results revealed higher pain scores for subjects receiving deltoid injections than gluteal injections (p<0.001). This is consistent with the smaller mass of the deltoid muscle, and with observations from other studies with injectable antipsychotics. The available data indicated mean increases in body weight of less than 1 kg at the end of the baseline treatment period. Greatest increases were observed in the baseline Consta group, although the difference between groups was not clinically relevant. Comparable small proportions of each group reported weight gain as an AE. Ergebnisse zu anderen Parametern: Nicht zutreffend Schlussfolgerung: The majority of subjects were treated according to the C- (39.3%), O- (45.2%) or C-O (9.7%) pattern during the 12-month prospective period. At baseline, subjects prescribed Consta had: more hospitalization time in the previous 6 months; worse symptom severity; a lower level of functioning and less treatment adherence than subjects prescribed oral antipsychotic therapy at baseline. Subjects prescribed Consta at baseline subsequently had reductions in days spent in hospital compared with the retrospective period; little change in hospitalization time was observed for subjects prescribed oral therapy at baseline. Greater improvements in symptomatic and functional outcomes, satisfaction with medication, and adherence to treatment were observed in subjects treated with Consta at baseline than in those treated with oral antipsychotic treatments. However, subjects starting oral antipsychotics were more likely to switch between NonConsta therapies than to switch to the long-acting injectable therapy Consta. This is surprising given the potential benefit of a long-acting injectable therapy in schizophrenia, a population characterized by high nonadherence rates. The complex switch patterns observed for a subset of subjects during this study suggest an unpredictable decision process in the search for an effective treatment. These complex treatment patterns were associated with less favorable treatment outcomes. There were no unexpected safety findings. EG, JMO/Februar 2011 Seite 8 von 8