Predicated upon uncontrolled reports suggesting aripiprazole might improve depressive symptoms in treatment-resistant unipolar major depressive disorder36 and bipolar disorder,37-38 two identical multicenter, double-blind trials were conducted to compare aripiprazole with placebo in BPI subjects experiencing a nonpsychotic major depressive episode.39 Subjects were entered into

an 8-week trial and initiated on aripiprazole 10 mg daily (5 mg twice Inhibitors,research,lifescience,medical daily), then flexibly dosed to 5 to 30 mg/day. In both studies, a pattern of early statistical significance emerged, but, during later study weeks this separation dissipated. By the trial end point, no significant, difference was found in either of the two trials on the Inhibitors,research,lifescience,medical primary efficacy measure of mean change from basclinc-to-cnd point, score on the MADRS. Similarly, no differences were observed on any of the secondary efficacy measures. When pooling study results, a large proportion of subjects receiving aripiprazole developed akathisia (24.4%) as compared with placebo-treated subjects (3.8%). It is unknown whether attempts to prevent, or mitigate akathisia

by initiating aripiprazole at doses lower than 10 mg/day or by aggressive and early use of P-blockcrs have the potential to enhance tolerability and improve measured efficacy. A summary of Inhibitors,research,lifescience,medical the trials discussed above can be seen in Table I. Table I. Pharmacological learn more treatments for bipolar depression: a summaiy of randomized, double-blind, parallel-group, placebo-controlled trials enrolling ≥subjects. ARP, aripiprazole; AST, aspartate aminotransferase; IDS-C, Inventory of Depressive Symptomatology-Clinician … Gauging clinical Inhibitors,research,lifescience,medical efficacy One means of comparing treatment, effects among different agents is through the use of effect size determinations (improvement over placebo divided by pooled standard deviation). With olanzapine monotherapy

the effect, size was small (0.32) but became moderate (0.68) with the addition of fluoxetine in bipolar I depression.31 The advantage of OFC over olanzapine alone was of the same magnitude as the difference favoring Inhibitors,research,lifescience,medical olanzapine alone over placebo.40 In BOLDER I, the effect size of quetiapine was large (-0.9) for both the 600 and 300 mg/day groups,33 but in the replication trial decreased to a moderate size.34 Apart from effect, size determinations, an alternate means of translating because research findings into clinically relevant terms is through calculation of the number needed to treat (NNT =l/responders on active compound minus responders on placebo). The NNT represents the number of patients who would require treatment with the drug under investigation in order for one additional patient to achieve the desired outcome. Hence, the NNT is a pragmatic means of comparing the magnitude of categorical response across various drug treatments. Cookson and colleagues41 calculated the NNT for rates of response and remission in the 8-week BOLDER I trial.