Systematic Review and Network Meta-analysis: Efficacy and Safety of Second-Generation Antipsychotics in Youths With Bipolar Depression.

OBJECTIVE: To assess the relative efficacy and safety of second-generation antipsychotics for treating major depressive episodes in youths with bipolar disorder. METHOD: A systematic literature review using PRISMA guidelines and network meta-analysis (NMA) of randomized controlled trials (RCTs) of second-generation antipsychotics for bipolar depression in youths 10 to 18 years of age was conducted. Efficacy measures included Children's Depression Rating Scale, Revised (CDRS-R) and Clinical Global Impressions-Bipolar Disorder-Severity Depression (CGI-BP-S-depression) and Overall (CGI-BP-S-overall) scores. Available safety outcomes included discontinuations (all-cause, lack of efficacy, adverse events), metabolic parameters (weight change, cholesterol, triglycerides, glucose), changes in prolactin, and somnolence. Results from the NMA were reported as mean changes from baseline or odds ratios (OR) with 95% credible intervals (CrIs). RESULTS: Four RCTs comparing placebo to lurasidone, quetiapine (1 each for immediate- and extended-release), and the olanzapine-fluoxetine combination (OFC) met all of the inclusion criteria. Lurasidone and OFC demonstrated similar and statistically significant improvements in CDRS-R, but quetiapine did not (lurasidone: -5.70 [-8.66, -2.76]; OFC: -5.01 [-8.63, -1.38]; quetiapine: -1.85 [-5.99, 2.27]). Lurasidone was associated with smaller changes in weight, cholesterol, and triglycerides from baseline compared to OFC and quetiapine. There were no differences in changes in glucose levels among antipsychotics. In addition, lurasidone was associated with smaller change in prolactin levels compared to OFC but not quetiapine. CONCLUSION: Evidence from 4 studies in this NMA indicated that lurasidone and OFC, but not quetiapine, were efficacious for the treatment of bipolar depression in youths. Lurasidone was associated with less weight gain and smaller impacts on cholesterol and triglycerides compared with quetiapine and OFC.

Healthcare resource utilisation and costs associated with a heart failure diagnosis: a retrospective, population-based cohort study in Sweden.

OBJECTIVES: To examine healthcare resource use (HRU) and costs among heart failure (HF) patients using population data from Sweden. DESIGN: Retrospective, non-interventional cohort study. SETTING: Two cohorts were identified from linked national health registers (cohort 1, 2005-2014) and electronic medical records (cohort 2, 2010-2012; primary/secondary care patients from Uppsala and Västerbotten). PARTICIPANTS: Patients (aged ≥18 years) with primary or secondary diagnoses of HF (≥2 International Classification of Diseases and Related Health Problems, 10th revision classification) during the identification period of January 2005 to March 2015 were included. OUTCOME MEASURES: HRU across the HF phenotypes was assessed with logistic regression. Costs were estimated based on diagnosis-related group codes and general price lists. RESULTS: Total annual costs of secondary care of prevalent HF increased from SEK 6.23 (€0.60) to 8.86 (€0.85) billion between 2005 and 2014. Of 4648 incident patients, HF phenotype was known for 1715: reduced ejection fraction (HFrEF): 64.5%, preserved ejection fraction (HFpEF): 35.5%. Within 1 year of HF diagnosis, the proportion of patients hospitalised was only marginally higher for HFrEF versus HFpEF (all-cause (95% CI): 64.7% (60.8 to 68.4) vs 63.7% (60.8 to 66.5), HR 0.91, p=0.14; cardiovascular disease related (95% CI): 61.1% (57.1 to 64.8) vs 60.9% (58.0 to 63.7), HR 0.93, p=0.28). Frequency of hospitalisations and outpatient visits per patient declined after the first year. All-cause secondary care costs in the first year were SEK 122 758 (€12 890)/patient/year, with HF-specific care accounting for 69% of the costs. Overall, 10% of the most expensive population (younger; predominantly male; more likely to have comorbidities) incurred ~40% of total secondary care costs. CONCLUSIONS: HF-associated costs and HRU are high, especially during the first year of diagnosis. This is driven by high hospitalisations rates. Understanding the profile of resource-intensive patients being at younger age, male sex and high Charlson comorbidity index scores at the time of the HF diagnosis is most likely a sign of more severe disease.

Efficacy and tolerability of atypical antipsychotics for acute bipolar depression: a network meta-analysis.

BACKGROUND: While clinical trial evidence has firmly established the efficacy of several atypical antipsychotics (AAPs) for treating bipolar depression, no randomized controlled trials (RCT's) comparing AAPs have been conducted. This Bayesian network meta-analysis (NMA) compared the relative efficacy and tolerability of AAP monotherapy in adults with bipolar depression. METHODS: Efficacy measures included change in Montgomery Åsberg Depression Rating Scale (MADRS), Clinical Global Improvement - Bipolar Disorder (CGI-BP), response, and remission. Multiple tolerability outcomes were examined. Results from random effects models were reported as difference in change from baseline for continuous variables or odds ratios for dichotomous variables. Treatments were ranked using the surface under the curve cumulative ranking probabilities. Number needed to treat (NNT) and harm (NNH) were calculated. RESULTS: Eighteen RCT's met inclusion criteria of the systematic literature review. On change in MADRS, lurasidone (- 4.71 [95% Crl - 6.98, - 2.41]), quetiapine (- 4.80 [- 5.93, - 3.72]), olanzapine (- 4.57 [- 5.92, - 3.20]), and cariprazine (- 2.29 [- 3.47, - 1.09]) were more efficacious than placebo. Lurasidone was associated with a significantly greater odds of response (≥50% improvement in MADRS) compared to cariprazine (1.78 [95% Crl 1.08, 2.77]), aripiprazole (2.38 [1.38, 3.85]), and ziprasidone (2.47 [1.41, 3.98]), but was similar to olanzapine (1.68 [0.99,2.65]) and quetiapine (1.25 [0.78, 1.90]). For change in CGI-BP-S-overall score, lurasidone was significantly better than cariprazine (- 0.38 [95% Crl - 0.66,-0.10]) and ziprasidone (- 0.58 [- 0.91,-0.26]), but similar to quetiapine (- 0.08 [- 0.36, 0.19])and olanzapine (- 0.04 [- 1.41, 1.46]). Lurasidone (0.34 kg [95% Crl - 0.22, 0.89]) and aripiprazole (0.20 kg [- 0.59, 1.00]) had a similar weight change compared to placebo, but olanzapine (2.88 kg [2.40, 3.36]), quetiapine (1.17 kg [0.84, 1.49]), and cariprazine (0.65 kg [0.34, 0.96]) were associated with greater weight gain. The NNT for response was the lowest for lurasidone (NNT = 5) followed by quetiapine (NNT = 6), olanzapine (NNT = 10) and cariprazine (NNT = 12). CONCLUSIONS: In this NMA in adults with bipolar depression, which evaluated change in depressive symptoms (assessed by MADRS) across short-term trials, the largest improvement versus placebo was observed for lurasidone, olanzapine and quetiapine with cariprazine, showing a smaller treatment effect. Aripiprazole and ziprasidone were ineffective for the treatment of bipolar depression. Improvement in CGI-BP-S score for lurasidone was larger than cariprazine and ziprasidone but similar to quetiapine and olanzapine. Based on short term studies lurasidone and aripiprazole had similar weight gain compared to placebo.