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Objective: To assess treatment patterns, health care resource utilization, and health care costs associated with use of atypical antipsychotics (AAPs) or the nonstimulant guanfacine extended release (GXR) after stimulant therapy for attention-deficit/hyperactivity disorder (ADHD). In Canada, GXR is approved as a monotherapy for children and adolescents with ADHD or as an adjunct to stimulants, and AAPs are commonly used off-label as an adjunct to stimulants. Methods: Health care claims data (January 1, 2007 to March 31, 2016) from Quebec's provincial health plan were assessed for individuals with ADHD, 6-17 years of age, who received ≥1 stimulant followed by a first AAP or GXR prescription (index medication), without a diagnosis for which AAPs are indicated. Results: Overall, 1327 individuals were included (AAPs, 1098; GXR, 229). Rates of discontinuation, augmentation, or switching of the index medication did not differ between AAPs and GXR during the first follow-up year. Discontinuation rates were significantly lower with GXR than with AAPs during the second year (22.0% vs. 35.9%; p = 0.03). GXR and AAPs resulted in similar increases in total health care cost. In GXR users, the increase in prescription drug cost after 6 months was higher than in AAP users, whereas the increase in overall medical cost was higher with AAPs than GXR, owing to more psychiatric department visits. Conclusions: In children and adolescents with ADHD who used AAPs or GXR after stimulants, secondary treatment changes were similar with both treatments after 1 year, but discontinuation rates were significantly lower with GXR than with AAPs in the second year. The greater increase in prescription cost with GXR was balanced by a greater increase in overall medical costs with AAPs, resulting in no overall difference in total health care cost between the two treatments. [ABSTRACT FROM AUTHOR]

Objective: Although antidepressants and antipsychotics are valuable medications in the treatment of select psychiatric disorders, there is increasing focus on the balance of risks and benefits of these drugs as prescribed, particularly in the pediatric population. We examined recent national trends and interprovincial variation in dispensing of antipsychotic and antidepressant prescriptions to the Canadian pediatric population.Method: We conducted a population-based cross-sectional study of antidepressant and antipsychotic prescriptions dispensed by Canadian pharmacies to the pediatric population (≤18 years) between 2010 and 2013. Prescription volumes were obtained from IMS Health. Analysis was stratified by drug, year, quarter, and province and population-standardized using age-adjusted population estimates.Results: From the first quarter of 2010 to the fourth quarter of 2013, dispensing of antipsychotics to the pediatric population increased 33% (from 34 to 45 prescriptions per 1000) and dispensing of antidepressants increased 63% (from 34 to 55 per 1000). We observed a 1.5-fold interprovincial difference in dispensing rates for antidepressants (range: 189 per 1000 to 275 per 1000) and a 3.0-fold difference for antipsychotics (range: 85 per 1000 to 253 per 1000) in 2013. Among antidepressants, selective serotonin reuptake inhibitors were the most dispensed (76%), with fluoxetine being the leading agent. Among antipsychotics, atypical antipsychotics were the most dispensed (97%), with risperidone being the leading agent.Conclusions: Antipsychotic and antidepressant dispensing to the Canadian pediatric population increased from 2010 to 2013, with considerable interprovincial variation. Future research is required to explore reasons for observed patterns to optimize care for the Canadian pediatric population. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives Second-generation antipsychotic agents have varying propensities to cause weight gain, elevated lipid levels and associated long-term complications. This study evaluates the cost-effectiveness of four second-generation antipsychotic agents used in Canada for the treatment of schizophrenia (ziprasidone, olanzapine, quetiapine, risperidone) with a focus on their long-term metabolic consequences. Method Using data from the Clinical Antipsychotic Trials of Intervention Effectiveness Study, a semi-Markov model was developed to predict the incidence and associated costs of type 2 diabetes, cardiovascular complications (e.g. angina, myocardial infarction, stroke, cardiovascular disease death), and acute psychiatric hospitalizations in patients with chronic schizophrenia treated over 5 years. Incremental costs per quality-adjusted life year (QALY) gained were calculated from the perspective of the Canadian provincial ministries of health. Scenario and probabilistic sensitivity analyses were performed. Results The total average cost of treatment with ziprasidone was $25 301 versus $28 563 with olanzapine, $26 233 with quetiapine and $21 831 with risperidone. Ziprasidone had the lowest predicted number of type 2 diabetes cases and cardiovascular disease events, and the highest QALY gains. Patients receiving quetiapine had the highest predicted number of hospitalizations. Ziprasidone was less costly and resulted in more QALYs compared with olanzapine and quetiapine. Compared with risperidone, ziprasidone was more costly and had higher QALYs, with an incremental cost per QALY gained of $218 060. Conclusion Compared with olanzapine and quetiapine, ziprasidone produced savings to the health care system. Although ziprasidone generated incremental expenditures versus risperidone, it resulted in more QALYs. Based on this analysis, ziprasidone treatment possesses cost and therapeutic advantages compared with olanzapine and quetiapine. [ABSTRACT FROM AUTHOR]

Objective: To evaluate over a 2-year period, patients from academic/non-academic centres, from each region of Canada, to determine whether location or other variables such as medication type, gender or income was associated with outcome as defined by non-hospitalization and persistence on original treatment. Method: A total of 448 patients were recruited from academic and non-academic centres across all provinces of Canada and followed up for 2 years. Results: Patients from British Columbia had significantly lower rates of hospitalization than patients from other provinces. Male patients showed greater symptomatic improvement at 2 years from initial assessment compared to females. Patients on clozapine, risperidone and olanzapine were least likely to be hospitalized. Conclusion: There were some regional differences noted in both utilization of types of antipsychotic medications and hospitalization rates. In this sample of stable out-patients over 70% who started on monotherapy with clozapine, risperidone, olanzapine and quetiapine remained on the same medication over the 2-year study period. [ABSTRACT FROM AUTHOR]

Schizophrenia is a chronic, relapsing disease that requires more healthcare resources to manage than any other single psychiatric illness. The main cost of treatment is hospitalization as a result of the exacerbation of symptoms often caused by poor compliance. Although the costs of hospitalization and relapse have been well documented, the differential effects of various medications on healthcare expenditure are still being determined. The aim of the present study was to estimate the cost effectiveness of long-acting risperidone in the treatment of high-risk, non-compliant patients with schizophrenia over a 5-year period in Canada. A discrete event model was developed comparing three scenarios, each with a different starting treatment: haloperidol depot, long-acting risperidone or oral risperidone. Second and third-line treatment options were olanzapine and clozapine, respectively, for all three scenarios. On the basis of 3000 simulated patient characteristics, the model generated individual patient histories. Outcomes included the number and duration of psychotic episodes, the cumulative Positive and Negative Syndrome Scale (PANSS) score and direct medical costs. The time horizon of the model was 5 years and a 5% discount rate was used for costs and effects. The perspective of the model was that of the Canadian healthcare system. After 5 years, treatment with long-acting risperidone saved Can$6908 and Can$13 130 (discounted) and avoided 0.28 and 0.54 relapses per patient, compared with haloperidol depot and oral risperidone, respectively. In this model, initiating treatment of high-risk, non-compliant patients with schizophrenia with long-acting risperidone was the dominant strategy. With long-acting risperidone, direct costs were lower and clinical effectiveness was greater, compared with haloperidol depot or oral risperidone, during years 4 and 5. [ABSTRACT FROM AUTHOR]

Clinical trials for the treatment of schizophrenia now often include cognitive assessments in addition to clinical ratings of symptoms. Recently, these trials have included cross-national assessments. It is not clear if translated psychological tests produce consistent results across different languages. This paper presents the results of a study of the comparability of the results of cognitive assessments in different English-speaking countries and a number of countries where tests were translated into other languages. Performance on tests of executive functioning, verbal and visuo-spatial learning and memory, language skills, psychomotor speed, and vigilance was compared across the first episode patients with schizophrenia (n=301) assessed in six different languages (English, French, Finnish, German, Hebrew, and Afrikaans), including two different countries where patients were assessed in English and other languages: Canada (French) and South Africa (Afrikaans). The variance in performance across the sites tested in English was as large as the variance between English and non-English speakers when all tests were considered. Performance differences across English and other languages were found only for executive functions, vigilance, and psychomotor speed, with executive functioning differences nonsignificant when education was considered. No differences were found between English and non-English speakers in Canada. These results suggest that the translation of tests of memory and verbal skills can lead to consistent results across translated versions of the tests. Differences between countries were greater than differences between languages, suggesting the need to consider representativeness of patient samples in terms of local educational attainment. In general, these data support the validity of cross-national neuropsychological assessments. [Copyright &y& Elsevier]

Objective: Given the renewed interest in the role of sex differences in schizophrenia, we undertook a post hoc analysis to determine whether sex differences in treatment response were present among outpatients with schizophrenia who received risperidone in an 8-week, open-label, Phase IV clinical study.Method: We evaluated 330 adult patients (232 men, 98 women) with a DSM-III-R diagnosis of schizophrenia for safety and 292 (206 men, 86 women) for efficacy. Antipsychotic and antiparkinsonian medications were discontinued at study entry. Treatment with risperidone was initiated at a dosage of 2 mg daily, increased to the target dosage of 6 mg daily by day 3, and maintained at 6 mg daily until day 14. The dosage was then maintained at 6 mg daily, increased or decreased by 2 mg daily each week, based on the patient's response. Risperidone treatment was given for 8 weeks; the permitted dosage range was 4 mg to 10 mg daily.Results: Both male and female participants responded well to risperidone treatment; by the final assessment day, they had experienced decreases from baseline in their total Positive and Negative Syndrome Scale (PANSS) scores of 41.0% and 36.5%, respectively. Most male (77%) and female (78%) participants were considered to be PANSS responders: risperidone was effective against both the positive and negative symptoms of schizophrenia. Both sexes showed improvements over baseline in the incidence and severity of parkinsonism, dystonia, and dyskinesia. No significant (P > 0.05) sex differences in treatment response were observed for any of the efficacy outcomes or in the incidence and severity of extrapyramidal symptoms (EPS).Conclusions: In this population of outpatients with chronic schizophrenia, both men and women responded well to flexible doses of risperidone. No significant sex differences were evident either in treatment response or in neurological side effects. The absence of sex differences in response to risperidone treatment may obviate the need for a sex-based differential dosing in schizophrenia management. [ABSTRACT FROM AUTHOR]

This section offers news briefs on the pharmaceutical sector as of January 2015. Health Canada has warned of the neurological adverse events associated with children receiving metoclopramide. Great Britain has restricted the prescription of domperidone-containing medicines. The European Medicine Agency has reviewed medicines containing the antihistamine hydroxyzine.

Examines the long-term health care resource use and costs before and after the initiation of risperidone treatment in patients with chronic schizophrenia in Saskatchewan. Hospital, physician, mental health and drug services; Economic effects; Accuracy of diagnostic information.

Objective: To compare inpatient hospital days of a group of "real world" schizophrenia-spectrum patients for 3 years prior to and 3 years after risperidone initiation.Method: This is a retrospective cohort study using a mirror-image design of hospital days in 120 patients over a 6-year period. Hospital admission and discharge information was obtained from chart review and database extraction at 3 outpatient treatment sites. The sample comprised all patients attending these clinics who were prescribed risperidone during the first year of the drug's release.Results: Patients separated into 3 treatment groups: those who were prescribed risperidone for 3 uninterrupted years (N = 35), those who interrupted but resumed risperidone use and were prescribed the drug at 3 years (N = 8), and those who discontinued risperidone during the 3-year follow-up period (N = 77). The group continuing risperidone to 3 years demonstrated a significant decrease in hospital days after risperidone treatment, in contrast to the other 2 groups. The reduction in inpatient days for the total sample was not statistically significant.Conclusion: In this outpatient clinic sample, the 29% of patients who continued on risperidone showed a significant reduction in inpatient hospital days, from an average of 17.2 days per year in the 3 years before risperidone treatment to an average of 2.1 days per year for the 3 years of risperidone treatment. [ABSTRACT FROM AUTHOR]

Objective: To determine if the inclusion of a placebo control in clinical trials of schizophrenia affects retention rates in the first 35 days of inclusion relative to trials that did not have a placebo control. Method: This was a retrospective study of 8 double-blind clinical trials, 5 of which had a placebo control while 3 did not. Using survival analysis, retention rates between the placebo-controlled trials (PCTs) and the nonplacebo-controlled trials (NPCTs) were compared. Screening and percentage improvement on Brief Psychiatric Rating Scale and Positive and Negative Syndrome Scale scores were compared. Results: Significantly more patients were retained in the 35-day period for NPCTs. Also, the PCT group had significantly more psychopathology at screening than did the NPCT group. Conclusions: Differences in retention rates between PCTs and NPCTs cannot be uniquely attributed to placebo itself. [ABSTRACT FROM AUTHOR]

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Objective: Atypical antipsychotics are thought not to elevate prolactin levels. The authors examined data suggesting that atypical antipsychotics do elevate prolactin levels but more transiently than typical antipsychotics.Method: Prolactin levels in 18 male patients with schizophrenia who were receiving atypical antipsychotics were monitored over the 24-hour period following administration of their daily oral dose of risperidone, olanzapine, or clozapine.Results: The baseline prolactin levels in patients receiving risperidone (mean=27 ng/ml, SD=14) were abnormally high, but baseline prolactin levels in patients receiving olanzapine (mean=9 ng/ml, SD=5) and clozapine (mean=9 ng/ml, SD=5) were not high. All three atypical antipsychotics caused a doubling of prolactin levels over baseline levels 6 hours after medication administration.Conclusions: These data suggest that these atypical antipsychotics raise prolactin levels, although the increases with olanzapine did not reach statistical significance. This suggests that the differences in the effects on prolactin levels of atypical and typical antipsychotics are not categorical but lie in the degree and duration of dose-induced prolactin elevation, attributable to the differential binding properties of each drug on pituitary dopamine D(2) receptors. [ABSTRACT FROM AUTHOR]

Objective: Lithium and valproate are commonly used either in monotherapy or in combination with atypical antipsychotics in maintenance treatment of bipolar I disorder; however, their comparative efficacy is not well understood. This study aimed to compare the efficacy of valproate and lithium on mood stability either in monotherapy or in combination with atypical antipsychotics., Methods: We performed a post hoc analysis using data from a 52-week randomized double-blind, placebo-controlled trial, that recruited 159 patients with recently remitted mania during treatment with lithium or valproate and adjunctive atypical antipsychotic therapy. Patients were randomized to discontinue adjunctive atypical antipsychotic at 0, 24 or 52 weeks., Results: No significant differences in efficacy were observed between valproate and lithium (hazard ratio: 0.99; 95% confidence interval: [0.66, 1.48]) in time to any mood event. Valproate with 24 weeks of atypical antipsychotic was significantly superior to valproate monotherapy in preventing any mood relapse (hazard ratio: 0.46; 95% confidence interval: [0.22, 0.97]) while lithium with 24 weeks of atypical antipsychotic was superior to lithium monotherapy in preventing mania (hazard ratio: 0.27; 95% confidence interval: [0.09, 0.85]) but not depression., Conclusion: Overall, this study did not find significant differences in efficacy between the two mood-stabilizing agents when used as monotherapy or in combination with atypical antipsychotics. However, study design and small sample size might have precluded from detecting an effect if true difference in efficacy existed. Further head-to-head investigations with stratified designs are needed to evaluate maintenance therapies.

Reports on studies conducted by researchers from Montreal, Canada on the use of risperidone in children with disruptive behavior disorders, low intelligence quotient and attention deficit-hyperactivity disorder (ADHD). Profile of the study subjects; Comparison of the effects of the drug on hyperactivity and other symptoms in patients with ADHD; Effects of long term use of risperidone.

Background: The treatment of schizophrenia with multiple antipsychotic drugs is common, but the benefits and risks are not known. Methods: In a randomized, double-blind study, we evaluated patients with schizophrenia and a poor response to treatment with clozapine. The patients continued to take clozapine and were randomly assigned to receive eight weeks of daily augmentation with 3 mg of risperidone or with placebo. This course of treatment was followed by an optional 18 weeks of augmentation with risperidone. The primary outcome was reduction in the total score for severity of symptoms on the Positive and Negative Syndrome Scale (PANSS). The secondary outcomes included cognitive functioning. Results: A total of 68 patients were randomly assigned to treatment. In the double-blind phase, the mean total score for the severity of symptoms decreased from baseline to eight weeks in both the risperidone and the placebo groups. There was no statistically significant difference in symptomatic benefit between augmentation with risperidone and placebo: 9 of 34 patients receiving placebo and 6 of 34 receiving risperidone responded to treatment (P=0.38). The mean difference in the change in PANSS scores from baseline to eight weeks between those receiving risperidone and those receiving placebo was 0.1 (95 percent confidence interval, −7.3 to 7.0). The verbal working-memory index showed a small decline in the risperidone group and a small improvement in the placebo group (P=0.02 for the comparison between the two groups in the change from baseline). The increase in fasting blood glucose levels was mildly greater in the risperidone group than in the placebo group (16.2 vs. 1.8 mg per deciliter [0.90 vs. 0.10 mmol per liter], P=0.04). The incidence and severity of other side effects did not differ between the two groups. Conclusions: In this short-term study, the addition of risperidone to clozapine did not improve symptoms in patients with severe schizophrenia. (ClinicalTrials.gov number, NCT00272584) N Engl J Med 2006;354:472-82. [ABSTRACT FROM AUTHOR]

Hospital costs for chronic schizophrenic patients consume a major share of the cost of mental health care. Despite the success of numerous community mental health programs, repeated hospital admission of schizophrenic patients is a significant problem. Effective therapy and compliance with that therapy are two important factors in reducing hospitalization. Adverse effects of antipsychotic agents, particularly extrapyramidal symptoms (EPS), negatively influence compliance. A new antipsychotic agent, risperidone, has demonstrated efficacy against both positive and negative symptoms of schizophrenia and has been associated with a low incidence of EPS. To assess the potential of risperidone therapy to reduce the number of days in the hospital, a retrospective analysis was undertaken of data from a year-long clinical trial of risperidone. For 27 patients who had completed 365 days of open-label therapy with risperidone, the number of hospital days during this period was compared with the number of hospital days in the preceding 365-day period, when the patients were receiving conventional antipsychotic medication. The mean number of hospital days was reduced from 106 to 85 days, for a 20% reduction (P = 0.003) after the initiation of risperidone. Three subgroups of patients were apparent: (1) those who had spent no time in the hospital in the pre-risperidone year, (2) those who had been continuously hospitalized in the pre-risperidone year, and (3) those who had spent part of the pre-risperidone year (3 to 165 days) in the hospital. A 73% reduction (P = 0.0009) in mean hospital days (from 49 to 13 days) was achieved in the third subgroup (n = 14). These findings suggest that risperidone may have a role in reducing hospital days for the chronic schizophrenic population.