Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer's disease.

BACKGROUND: Mibampator, an amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor potentiator, was evaluated for treatment of agitation and aggression (A/A) in Alzheimer's disease (AD). METHODS: Outpatients (n = 132) with probable AD and A/A randomized to 12 weeks of double-blind treatment with 3-mg po mibampator or placebo were assessed using the 4-domain A/A subscale of the Neuropsychiatric Inventory (NPI-4-A/A) derived from the Neuropsychiatric Inventory. Secondary measures included the Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia, Frontal Systems Behavior Inventory (FrSBe), and Alzheimer's Disease Assessment Scale-Cognitive. Efficacy was analyzed using mixed-effects model repeated measures from baseline to endpoint. Adverse events (AEs), labs, vital signs, and electrocardiograms were monitored. RESULTS: Baseline characteristics were comparable between groups. Both groups improved on the NPI-4-A/A, but without group differences. Among secondaries, mibampator was significantly better (p = 0.007) than placebo only on the FrSBe. AEs were similar between groups. One death occurred in the placebo group. CONCLUSION: Possible explanations for no significant group differences include caregiver, drug target engagement, and design issues. This trial is registered on ClinicalTrials.gov; ID: NCT00843518.

Influence of sub-syndromal symptoms after remission from manic or mixed episodes.

BACKGROUND: Sub-syndromal symptoms in bipolar disorder impair functioning and diminish quality of life. AIMS: To examine factors associated with time spent with sub-syndromal symptoms and to characterise how these symptoms influence outcomes. METHOD: In a double-blind randomised maintenance trial, patients received either olanzapine or lithium monotherapy for 1 year. Stepwise logistic regression models were used to identify factors that were significant predictors of percentage time spent with sub-syndromal symptoms. The presence of sub-syndromal symptoms during the first 8 weeks was examined as a predictor of subsequent relapse. RESULTS: Presence of sub-syndromal depressive symptoms during the first 8 weeks significantly increased the likelihood of depressive relapse (relative risk 4.67, P<0.001). Patients with psychotic features and those with a greater number of previous depressive episodes were more likely to experience sub-syndromal depressive symptoms (RR=2.51, P<0.001 and RR=2.35, P=0.03 respectively). CONCLUSIONS: These findings help to identify patients at increased risk of affective relapse and suggest that appropriate therapeutic interventions should be considered even when syndromal-level symptoms are absent.