Efficacy and tolerability of extended release quetiapine fumarate monotherapy as maintenance treatment of major depressive disorder: a randomized, placebo-controlled trial.
BACKGROUND



OBJECTIVE
evaluate the efficacy (time to recurrence of depressive symptoms) of once daily extended release quetiapine fumarate (quetiapine XR) as maintenance monotherapy treatment to prevent relapse for major depressive disorder (MDD).


METHODS
Time-to-event (maximum 52 weeks), double-blind, multicenter, randomized withdrawal, placebo-controlled study of quetiapine XR (50-300 mg/day) comprising four treatment phases: enrollment (up to 28 days), open-label run-in (4-8 weeks), open-label stabilization (12-18 weeks), and randomization (up to 52 weeks). Seven hundred and seventy-six patients stabilized on quetiapine XR were eligible for randomization (Montgomery-Åsberg Depression Rating Scale [MADRS] score ≤12 and Clinical Global Impression-Severity of Illness [CGI-S] score ≤3); 391 received quetiapine XR and 385 received placebo (same dose as last open-label visit). Primary endpoint: time to recurrence of depressive event from randomization. Secondary outcomes included changes from randomization in MADRS total, CGI-S, Pittsburgh Sleep Quality Index (PSQI) global, and Hamilton Anxiety Rating Scale (HAM-A) total scores. Adverse events were recorded throughout.


RESULTS
Risk of recurrence of depressive event was significantly (P<.001) reduced by 66% (HR=.34; 95% CI: .25, .46) in patients randomized to continue with quetiapine XR versus patients randomized to switch to placebo. During the randomized phase, quetiapine XR maintained improvements in secondary outcomes (P<.001 for all): MADRS (0.15 versus 2.03), CGI-S (-0.03 versus 0.23); PSQI global (0.06 versus 1.35), and HAM-A total score (0.20 versus 1.58), respectively. The most common AEs (>10% any group) during the randomized period were headache and insomnia.


CONCLUSIONS
Quetiapine XR maintenance therapy significantly reduced the risk of a depressive event in patients with MDD stabilized on quetiapine XR, with a safety and tolerability profile consistent with the known profile of quetiapine.
Liebowitz
Michael
M
Department of Psychiatry, Columbia University, New York, New York 10128, USA. mrl1945@aol.com
Lam
Raymond W
RW
Lepola
Ulla
U
Datto
Catherine
C
Sweitzer
Dennis
D
Eriksson
Hans
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D055502:Secondary Prevention; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D003987:Dibenzothiazepines; D010919:Placebos; D000069348:Quetiapine Fumarate