Self-reported sedation profile of quetiapine extended-release and quetiapine immediate-release during 6-day initial dose escalation in bipolar depression: a multicenter, randomized, double-blind, phase IV study.
BACKGROUND
A human-volunteer study reported lower sedation intensity during escalation of the extended-release formulation of quetiapine fumarate (quetiapine XR) than the immediate-release (IR) formulation.


OBJECTIVE
To test the hypothesis that the profile of initial tolerability, including sedation, differs between the extended-release (XR) and immediate-release (IR) formulations of quetiapine in patients with bipolar depression.


METHODS
In a randomized, double-blind, double-dummy, parallel-group, Phase IV study, male and female inpatients aged 18 to 50 years with a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnosis of bipolar I or II depression were randomized after washout to receive placebo on day 1 and quetiapine XR or IR at escalating doses of 50, 100, 200, 300, and 300 mg once daily on the evenings of days 2 to 6, with hospital discharge on day 7. Sedation intensity was assessed by a self-reported modified Bond-Lader visual analog scale (VAS) score.


RESULTS
Of 139 randomized patients, 134 completed the study. Mean patient age was 39.0 years; mean weight, 91.3 kg; and mean body mass index (calculated as weight in kilograms divided by height in meters squared), 31.0. Sedation intensity 1 hour after administration of the 50-mg dose (the primary study measure) was statistically significantly lower with quetiapine XR versus IR (mean [SD] VAS score: 33.4 [26.92] vs 44.0 [31.76]; least squares mean difference: 12.55, P = 0.009; modified intention-to-treat population). Sedation intensity was found in secondary analyses to be significantly lower with quetiapine XR than with quetiapine IR 1, 2, and 3 hours after each dose on days 2 to 6 (P ≤ 0.05), with similar sedation intensity between the treatment groups 4 to 14 hours postdose. Rates of treatment-related adverse events were 47.1% with quetiapine XR versus 59.4% with quetiapine IR. Three serious adverse events (4.3%) occurred in the quetiapine XR group. Adverse events led to study discontinuation in 1 patient (1.4%) in the quetiapine XR group and in 2 patients (2.9%) in the IR group.


CONCLUSIONS
During the initial dose-escalation period studied, patients with bipolar depression reported statistically significantly lower sedation intensity in the 1 to 3 hours after taking quetiapine XR compared with the IR formulation. Overall tolerability for both formulations was consistent with the known profile of quetiapine. ClinicalTrials.gov identifier: NCT00926393.
Atlanta Center for Medical Research, Atlanta, Georgia 30308, USA. rriesenberg@acmr.org
Robert A
RA
Riesenberg
Irina
I
Baldytcheva
Catherine
C
Datto
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D003987:Dibenzothiazepines / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D057566:Self Report; D012890:Sleep / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014851:Wakefulness / Q000187:drug effects*; D055815:Young Adult
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D003987:Dibenzothiazepines; D006993:Hypnotics and Sedatives; D000069348:Quetiapine Fumarate