Treatment of acute schizophrenia with paliperidone ER: predictors for treatment response and benzodiazepine use.

The Paliperidone ER Treatment in Acute Intervention (PERTAIN) study was designed to explore treatment response, tolerability, and safety of flexible doses of paliperidone ER in patients with schizophrenia admitted for an acute exacerbation. This paper addresses a secondary analysis of PERTAIN data designed to explore predictors for treatment response, flexible dosing, and concomitant benzodiazepine use. This prospective, multicenter, phase 3b, open-label, single-arm, 6-week study used flexible doses of paliperidone ER (3 to 12mg once daily) to treat patients hospitalized for an acute exacerbation of schizophrenia, reflecting more closely daily clinical practice. Predictive models were evaluated for paliperidone ER flexible dosing, treatment response, and concomitant treatment with benzodiazepines as distinct independent variables. For the analysis of explanatory variables, a stepwise logistic regression was used, taking into account patient age, gender, body mass index, diagnosis and duration of schizophrenia, number of prior hospitalizations, psychotic symptoms (PANSS), disease severity (CGI-S), and patient functioning (PSP) at baseline. Early response (defined as response within 2weeks of treatment initiation) was also used as a predictor. Clinical response (defined as ≥30% decrease in PANSS total score and ≥1 point decrease in CGI-S from baseline to endpoint) was predicted by early clinical response (p<0.001) and there was a trend for the diagnosis of paranoid schizophrenia vs. other types of schizophrenia to predict clinical response (p=0.0525). High response (defined as ≥50% decrease in PANSS total score and ≥2 points decrease in CGI-S from baseline to endpoint) was predicted by early high response, higher baseline CGI-S, or female gender. More severely ill patients with a higher baseline CGI-S were twice likely to be treated concomitantly with a benzodiazepine.

Treatment discontinuation and clinical outcomes in the 1-year naturalistic treatment of patients with schizophrenia at risk of treatment nonadherence.

BACKGROUND: This study aimed to improve physicians' understanding of the treatment circumstances and needs of outpatients with schizophrenia at risk of nonadherence, by naturalistically assessing antipsychotic treatment patterns, clinical outcomes, and health care service use in this little-studied patient population. METHODS: In this one-year, prospective, multicenter, noninterventional, observational study, patients considered at risk of nonadherence by their physicians were switched from their primary oral antipsychotic to another oral or a depot antipsychotic at study entry. All cause treatment discontinuation (antipsychotic switch, augmentation, or discontinuation) during the study was assessed using Kaplan-Meier survival analyses and descriptive statistics. Patients' illness severity, quality of life, attitude towards medication, patient-reported adherence, and health care resource utilization were assessed during the study. RESULTS: Of the 406 enrolled patients, 43 (10.6%) were switched to depot and 363 (89.4%) were switched to oral antipsychotics at study entry. During the study, 99 (24.4%) patients switched, augmented, or discontinued their antipsychotic (all cause treatment discontinuation). Of the 99 patients who switched, augmented, or discontinued their antipsychotic, 8 (18.6%) were taking depot and 91 (25.0%) were taking oral antipsychotics. These patients were switched to either depot (n = 15) or oral (n = 78) antipsychotics, or discontinued their antipsychotic medication (n = 6). Inadequate response was the most frequently reported reason for medication discontinuation. During the study, patients' clinical and functional status improved significantly and service use was low. Most patients considered themselves to be adherent at study entry, and this favorable self-perception increased during the study (from 68.5% to 88.1%). CONCLUSION: Although identified as at risk of nonadherence, few patients in this naturalistic study discontinued their prescribed antipsychotic medication during the study. The discrepancy between the physicians' perception of their patient's medication adherence and the patients' self-perceived adherence highlights the need to better understand the underlying reasons for this phenomenon.

Safety and efficacy of long-acting injectable risperidone in daily practice: an open-label, noninterventional, prospective study in schizophrenia and related disorders.

This postauthorization safety study evaluated the long-term safety, tolerability, and efficacy of risperidone long-acting injectable (RLAI) in routine clinical practice. In this 6-month, multicenter, European, naturalistic study, patients were included if, during routine clinical practice, long-term antipsychotic therapy with RLAI was deemed necessary by the treating physician. Efficacy measures included Clinical Global Impression-Severity and Global Assessment of Functioning. Safety was evaluated by recording treatment-emergent adverse events (AE). RLAI was initiated in 5134 patients (aged 14-94 years); predominantly male (58.6%) with paranoid schizophrenia (69.8%). RLAI initial doses were 25 mg every 2 weeks (37.0% patients), 37.5 mg (18.0%), and 50 mg (44.4%). Treatment was completed by 4314 patients (84.0%). RLAI was discontinued on account of loss to follow-up (n=346; 6.7%), insufficient response (n=116; 2.3%), and AEs (n=106; 2.1%). Clinical Global Impression-Severity significantly improved from baseline to endpoint (P<0.001). Patient functioning on the Global Assessment of Functioning scale also significantly improved from baseline to endpoint (45.4 + or - 16.0 vs. 62.4 + or - 17.7, respectively, P<0.001). Treatment-emergent AEs were recorded by 1018 (20%) of patients. AEs occurring in > or = 5% of patients were akathisia, extrapyramidal disorders, depression, psychotic disorder, anxiety, and weight gain. Serious AEs were reported by 384 (8%) patients. This study confirms good safety, tolerability, and efficacy with RLAI in routine clinical practice.