Clinical Global Impressions-Bipolar Severity Research Articles

Efficacy and Safety of Lurasidone in a Younger Population With Bipolar Depression: Pooled Post-hoc Analysis of Two Placebo-controlled Studies

AbstractIntroductionEarly onset of bipolar disorder is associated with high rates of psychiatric comorbidity (e.g., anxiety disorders, ADHD, PTSD), high rates of recurrence, and marked impairment in functioning and quality of life. The aim of this analysis was to evaluate the efficacy and safety of lurasidone in bipolar depression in youth and young adult patients (10–30 years old).MethodsData from two 6-week, double-blind, placebo-controlled studies of lurasidone monotherapy for bipolar I depression were pooled for this analysis. In the 1st study, patients 10–17 years old were evaluated using the Children’s Depression Rating Scale–Revised (CDRS-R) and the Clinical Global Impression-Bipolar Severity (CGI-BP-S) depression scale; in the 2nd study, a subgroup of adult patients (18–30 years old) were evaluated by CGI-BP-A, and the MADRS, with the latter being converted to a CDRS-R scores using a validated conversion algorithm.ResultsThe safety population consisted of 465 patients (mean age, 17.1 years; mean age of onset, 14.1; mean CDRS-R total score, 60.8). 400 patients (85.7%) completed the study. For lurasidone vs. placebo, LS mean Week 6 change was -21.4 vs. -15.3 for the CDRS-R total score (P<0.0001; ES, 0.46); and -1.6 vs. -1.1 for the CGI-BP-S score (P<0.0001; ES, 0.50). Adverse events (≥5%) on lurasidone vs. placebo were nausea (15.9% vs. 5.2%), headache (15.1% vs. 13.1%), somnolence (7.9% vs. 3.8%), vomiting (5.2% vs. 3.3%), and weight increase (5.2% vs. 2.3%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin.ConclusionsIn this post-hoc analysis of two placebo-controlled trials, lurasidone demonstrated clinically meaningful improvement of depressive symptoms in youth and young adults with bipolar depression. Lurasidone was generally safe, well-tolerated, and associated with minimal effects on weight, metabolic parameters, and prolactin.FundingServier Laboratories (Aust.) Pty. Ltd., and Sunovion Pharmaceuticals Inc.

A Randomized, Double-Blind, Controlled Trial of Lithium Versus Quetiapine for the Treatment of Acute Mania in Youth with Early Course Bipolar Disorder.

Objective: To compare the efficacy and tolerability of lithium versus quetiapine for the treatment of manic or mixed episodes in youths with early course bipolar I disorder. Methods: Six-week, randomized, double-blind clinical trial of lithium versus quetiapine for the treatment of adolescents with acute manic/mixed episode. Target dose of quetiapine dose was adjusted to a target dose of 400-600 mg and target serum level for lithium was 1.0-1.2 mEq/L. Primary outcome measure was baseline-to-endpoint change in the Young Mania Rating Scale (YMRS). Secondary outcomes were treatment response (50% or more decrease from baseline in YMRS score) and remission (YMRS score ≤12, Children's Depression Rating Scale-Revised [CDRS-R] total score ≤28 and Clinical Global Impression Bipolar Severity Scale [CGI-BP-S] overall score of ≤3, respectively). Results: A total of 109 patients were randomized (quetiapine = 58 and lithium = 51). Participants in the quetiapine treatment group showed a significantly greater reduction in YMRS score than those in the lithium group (-11.0 vs. -13.2; p < 0.001; effect size 0.39). Response rate was 72% in the quetiapine group and 49% in the lithium group (p = 0.012); no differences in remission rates between groups were observed. Most frequent side effects for lithium were headaches (60.8%), nausea (39.2%), somnolence (27.5%), and tremor (27.5%); for quetiapine somnolence (63.8%), headaches (55.2%), tremor (36.2%), and dizziness (36.2%) were evidenced. Participants receiving quetiapine experienced more somnolence (p < 0.001), dizziness (p < 0.05), and weight gain (p < 0.05). Conclusions: Treatment with both lithium and quetiapine led to clinical improvement. Most study participants in this study experienced a clinical response; however, less than half of the participants in this study achieved symptomatic remission. The head-to-head comparison of both treatment groups showed quetiapine was associated with a statistically significant greater rate of response and overall symptom reduction compared with lithium. Trial registration: clinicaltrials.gov NCT00893581.

Adjunctive Aripiprazole in Bipolar I Depression

Aripiprazole has demonstrated efficacy in treatment of bipolar mania, as well as in the maintenance treatment of bipolar disorder. There has been only one report supporting a role for this agent in the depressed phase of the illness. To evaluate the effectiveness of adjunctive aripiprazole in bipolar I depressed patients who are nonresponders to standard therapy. Chart records were reviewed for all patients with bipolar I depression, diagnosed by Diagnostic and Statistical Manual of Mental Disorders, 4th revision, criteria between June 2004 and January 2006 from the Long Beach Veterans Affairs Mood Disorders Clinic. Included subjects had experienced moderate to marked depressive symptoms (Clinical Global Impression-Bipolar Depression > or =4) despite at least 2 months of treatment with adequate doses of at least one mood stabilizer. In addition, all subjects had been treated subsequently with aripiprazole 15-30 mg/day added to the existing regimen. Detailed chart notes were used to retrospectively rate symptoms. The presence or absence of each symptom was recorded before and after aripiprazole augmentation. Based on these data, Clinical Global Impression bipolar severity (CGI-BP-S) ratings and CGI-BP improvement scores for bipolar I depression were assigned. Ten subjects met study criteria. Adjunctive aripiprazole given for 21-110 days resulted in significant improvements in CGI-BP-S depression ratings. Seven of 10 patients were assigned CGI-BP improvement ratings of much or very much improved. Adverse events were mild and included akathisia, nausea, and insomnia. Dose adjustments of aripiprazole or the addition of drugs to treat adverse effects excluded subjects from further data collection. No patient stopped aripiprazole due to adverse effects. This study adds to a previous report indicating beneficial effects of adjunctive aripiprazole in treatment of bipolar I depression. Double-blind, placebo-controlled investigations are needed to confirm these findings.