The BOLDER Study Group Objective: There is a major unmet need for effective options in the treatment of bipolar depression. Method: Five hundred forty-two outpatients with bipolar I (N=360) or 11 (N=182) disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 8 weeks of quetiapine (600 or 300 mgl day) or placebo. The prima ry efficacy measure was mean change from base))ne to week 8 in the Montgomery-Asberg Depression Rating Scale total score. Additional efficacy assessments included the Hamilton Depression Rating Scale, Clinical Global Impression of severity and improvement, Hamilton Anxiety Rating Sea Ie, Pittsburgh Sleep Quality Index, and Quality of life Enjoyment and Satisfaction Questionnaire. Results: Quetiapine at either dose demonstrated statistically significant improvement in Montgomery-Asberg Depression Rating Scale total scores compared with placebo from week 1 onward. The proportions of patients meeting response criteria (250% Montgomery-Asberg Depression Rating Scale score improvement) at the final assessment in the groups taking 600 and 300 mglday of quetiapine were 58.2% and 57.6%, respectively, versus 36.1 % for placebo. The proportions of patients meeting remission criteria (Montgomery-Asberg Depression Rating Scale :5::12) were 52.9% in the groups taking 600 and 300 mg/day of quetiapine versus 28.4% for placebo. Quetiapine at 600 and 300 mglday significantly improved 9 of 10 and B of 10 Montgomery-Asberg Depression Rating Scale items, respectively, compa red to placebo, including the core sym ptoms of depression_ Treatmentemergent mania rates were low and similar for the quetiapine and placebo groups (3.2% and 3.9%, respectively). Conclusions: Quetiapine monotherapy is effkacious and well tolerated for the treatment of bipolar depression.

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IMPORTANCE Alzheimer disease (AD) is a neurodegenerative disorder characterized by cognitive deterioration and impaired activities of daily living. Current treatments provide only minor symptomatic improvements with limited benefit duration. Lanabecestat, a brain-permeable inhibitor of human beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1/β-secretase), was developed to modify the clinical course of AD by slowing disease progression. OBJECTIVE To assess whether lanabecestat slows the progression of AD compared with placebo in patients with early AD (mild cognitive impairment) and mild AD dementia.