Although much has been reported on the short-term outcomes of functional endoscopic sinus surgery (FESS), little has been reported with regard to its long-term impact on chronic sinusitis. The senior author (D.W.K.) previously reported detailed subjective and endoscopic follow-up on 120 patients at a mean of 18 months following surgery. This current study represents a long-term follow-up (average, 7.8 years) of 72 patients (60%) from the same cohort. Of patients responding to a question about overall symptoms, 98.4% (n = 66) reported improvement compared with before surgery. There was a trend toward continued subjective improvement in symptom scores with longer follow-up, but the changes did not reach statistical significance. Thirteen patients (18%) required subsequent surgical procedures. Preoperative stage, prior surgery, and other factors that might affect outcome were evaluated. The study demonstrates that excellent subjective results following FESS can be maintained in the long term with appropriate postoperative management. The study also validates the concept that patients in whom the cavity can be normalized following surgery are unlikely to require further surgery.

PTC Therapeutics.

Monotherapy with lurasidone in the dosage range of 20-120 mg/day significantly reduced depressive symptoms in patients with bipolar I depression. Lurasidone was well tolerated, with few changes in weight or metabolic parameters.

OBJECTIVE Few studies have been reported that support the efficacy of adjunctive therapy for patients with bipolar I depression who have had an insufficient response to monotherapy with mood-stabilizing agents. The authors investigated the efficacy of lurasidone, a novel antipsychotic agent, as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression. METHOD Patients were randomly assigned to receive 6 weeks of double-blind adjunctive treatment with lurasidone (N=183) or placebo (N=165), added to therapeutic levels of either lithium or valproate. Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP), respectively. RESULTS Lurasidone treatment significantly reduced mean MADRS total score at week 6 compared with the placebo group (-17.1 versus -13.5; effect size=0.34). Similarly, lurasidone treatment resulted in significantly greater endpoint reduction in CGI-BP depression severity scores compared with placebo (-1.96 versus -1.51; effect size=0.36) as well as significantly greater improvement in anxiety symptoms and in patient-reported measures of quality of life and functional impairment. Discontinuation rates due to adverse events were 6.0% and 7.9% in the lurasidone and placebo groups, respectively. Adverse events most frequently reported for lurasidone were nausea, somnolence, tremor, akathisia, and insomnia. Minimal changes in weight, lipids, and measures of glycemic control were observed during treatment with lurasidone. CONCLUSIONS In patients with bipolar I depression, treatment with lurasidone adjunctive to lithium or valproate significantly improved depressive symptoms and was generally well tolerated.

No abstract

ISRCTN Register: ISRCTN45537485 .

In this study, designed to evaluate the efficacy of lurasidone as adjunctive therapy with lithium or valproate, patients with bipolar I depression were randomized to 6 weeks of double-blind treatment with lurasidone (N = 180) or placebo (N = 176), added to background treatment with lithium or valproate. All patients were treated with lithium or valproate for a minimum of 4 weeks prior to screening. This was confirmed either by prospective treatment after study enrolment (run-in cohort), or retrospectively, with blood levels of lithium and valproate at screening (non-run-in cohort). Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP-S), respectively. Treatment with lurasidone was associated with non-significant improvement at week 6 vs. placebo for the MADRS total score (-11.8 vs -10.4; P = 0.176), and the CGI-BP-S score (-1.36 vs -1.13; P = 0.095). Significant separation from placebo was observed from weeks 2-5 for the MADRS and weeks 3-5 for the CGI-BP-S. Improvement in the placebo-subtracted MADRS total score was notably larger at week 6 for the non-run-in cohort compared to the run-in cohort (LS mean difference in endpoint change scores, -4.6; P = 0.009). Adverse events most frequently reported for lurasidone were akathisia, somnolence, and extrapyramidal side effects. In conclusion, lurasidone adjunctive with lithium or valproate demonstrated significant improvement in depressive symptoms based on the MADRS from weeks 2-5 but not at the primary week 6 endpoint.

Objective: Mixed (subsyndromal hypomanic) features are prevalent in patients with bipolar depression and are associated with more severe and complex illness, including increased risk for suicide attempts, higher switch to mania during antidepressant therapy, and a higher rate of recurrence. The aim of this post hoc analysis was to evaluate the efficacy and safety of lurasidone in the treatment of patients with bipolar depression presenting with mixed features.