A 6-year open-label study of the efficacy and safety of olanzapine long-acting injection in patients with schizophrenia: a post hoc analysis based on the European label recommendation.

PURPOSE: To assess the long-term efficacy and safety of olanzapine long-acting injection (LAI) in the treatment of schizophrenia, focusing on clinical trial data consistent with the approved indication and dosing recommendations in the European label and which forms the basis for treatment decisions made by clinicians in daily clinical practice. PATIENTS AND METHODS: This was a post hoc analysis of a 6-year open-label study of olanzapine LAI in patients (male or female, 18-75 years old) with schizophrenia entering this study following feeder studies of olanzapine LAI. Patients were flexibly dosed (45-405 mg, 2- to 4-week intervals), but those receiving oral olanzapine supplementation whose total olanzapine dose was >20 mg/day equivalent were excluded from this post hoc analysis. RESULTS: Data from 669 patients were analyzed (44.5% completed). Positive and Negative Syndrome Scale total scores did not change significantly from baseline to endpoint; Clinical Global Impression-Severity scores improved significantly. Mean weight change was +2.19 kg (P<0.001), with 40.8% of patients experiencing ≥7% weight gain. There were 24 occurrences of post-injection delirium/sedation syndrome (PDSS). CONCLUSION: Olanzapine LAI appeared to be effective in the long-term maintenance of schizophrenia, and the safety profile was consistent with that of oral olanzapine, except for injection-related events and PDSS events.

Safety and tolerability of atomoxetine in treatment of attention deficit hyperactivity disorder in adult patients: an integrated analysis of 15 clinical trials.

The safety profile of atomoxetine in the treatment of attention deficit hyperactivity disorder has been studied in many clinical trials. We performed an integrated safety analysis of 15 clinical trials in adults with attention deficit hyperactivity disorder. The analysis pooled patient data into three groups: acute placebo-controlled trials; long-term placebo-controlled trials; all trials. In total, 4829 adults (18-77 years, median: 36 years) were exposed to atomoxetine. Statistically significantly more atomoxetine-treated than placebo-treated patients experienced treatment-emergent adverse events (81.3% vs. 68.3% acute; 90.6% vs. 76.8% long term) and discontinued due to adverse events (8.9% vs. 4.0% acute; 17.9% vs. 6.3% long term). No statistically significant differences were observed in the proportion of patients experiencing serious adverse events. No previously unknown adverse events were identified. The most common adverse events included nausea, dry mouth, decreased appetite, insomnia and erectile dysfunction. Mean increases in heart rate (+5.2 beats per min) and blood pressure (systolic +2 mmHg, diastolic +1.9 mmHg) were modest. The proportion of patients experiencing clinically significant increases in blood pressure and heart rate at any time was statistically significantly higher with atomoxetine (systolic blood pressure 13-17%, diastolic blood pressure 37-40%, heart rate 42-43%) compared to placebo (systolic blood pressure 8-13%, diastolic blood pressure 29-34%, heart rate 21-26%). There was no increased risk of suicidal ideation or behaviour. Our findings confirm atomoxetine's known safety profile. From a safety perspective, atomoxetine is a useful treatment option for adults with attention deficit hyperactivity disorder.

Compliance as a stable function in the treatment course of bipolar disorder in patients stabilized on olanzapine: results from a 24-month observational study.

Compliance is a key factor in the maintenance treatment of bipolar disorder. This noninterventional study was conducted to explore factors associated with higher levels of compliance in bipolar patients, all treated in routine clinical settings. Bipolar outpatients (Clinical Global Impression of Severity score ≤3) who had been stabilized with olanzapine mono- or combination therapy for ≥4 weeks were enrolled in the study. Compliance to medication was assessed at baseline and after 3, 6, 9, 12, 18, and 24 months by a physician-rated, 4-point categorical scale using the following classification: noncompliant (patients being compliant to treatment schedule less than 20% of the time) and low (20% to 59% of the time), moderate (60% to 79% of the time), and high (≥80% of the time) levels of compliance. Both baseline and post-baseline factors were used in a generalized estimating equations (GEE) model to predict the likelihood of high compliance. Of 891 eligible patients, 657 patients completed the 24-month observation period. High levels of compliance (≥80%) were observed in 67% of patients at baseline, increasing to 80% in study completers. High compliance at baseline was identified as a strong predictor of compliance during study participation (odds ratio (OR) = 6.9, 95% confidence interval (CI) = 5.0 to 9.5, p < 0.001). Factors associated with high compliance during the study (GEE model) included greater life satisfaction (p = 0.002), better insight into illness (p < 0.001), less work impairment (p = 0.007), and fewer days of inpatient care (p = 0.002). Compliance ratings varied by country (p < 0.001) and duration of post-baseline treatment (p = 0.014). In conclusion, a number of clinical, functional, and social factors were identified as predictors of compliance in patients with bipolar disorder. As compliance is crucial for the long-term management of these patients, more attention should be directed towards compliance itself and factors associated with compliance levels in everyday treatment settings.