Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder

Abstract

Prospectively planned pooled analysis evaluating the efficacy of quetiapine extended release (XR) monotherapy in major depressive disorder (MDD). Data were pooled from two 6-week, randomized, double-blind, placebo-controlled studies of quetiapine XR in outpatients with MDD. The primary endpoint was Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from randomization at week 6. Other evaluations were MADRS response/remission, Hamilton Rating Scale for Anxiety, and subgroup analyses. A total of 968 patients were randomized to quetiapine XR, 150 mg/day (n=315), 300 mg/day (n=323), or placebo (n=330). The mean MADRS total score reductions from randomization were significant at week 6 with quetiapine XR, 150 mg/day (-14.7; P<0.001) and 300 mg/day (-14.7; P<0.001) versus placebo (-11.1), with significant reductions versus placebo from week 1 onward. Response rates (week 6): 52.7% (P<0.001) quetiapine XR 150 mg/day and 49.5% (P<0.001) quetiapine XR 300 mg/day versus placebo (33.0%). MADRS remission (score≤8; week 6): 23.5% (P=0.208) quetiapine XR 150 mg/day and 28.8% (P<0.01) quetiapine XR 300 mg/day versus placebo (19.4%). Quetiapine XR (both doses) significantly improved eight of 10 MADRS items versus placebo at week 6. The therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as sex, age, or severity of depression. In patients with MDD, quetiapine XR (150 and 300 mg/day) monotherapy reduced depressive symptoms, with significant improvements compared with placebo from week 1 onward.

Quetiapine Fumarate Extended‐Release for the Treatment of Major Depression With Comorbid Fibromyalgia Syndrome: A Double‐Blind, Randomized, Placebo‐Controlled Study

“…Efficacy was also demonstrated for numerous secondary depression-related end points, including change from baseline in the mean HAM-A anxiety scores; CGI severity, improvement, and depression scores; GAS score; and percentage of patients who achieved response or remission for both depressive (HAM-D) and anxiety (HAM-A) symptoms. Our findings support the results of several studies demonstrating the antidepressant efficacy of quetiapine XR as monotherapy for patients with MDD (27)(28)(29).…”

“…Fatigue is a commonly cited symptom among patients with fibromyalgia (2,3); therefore, this effect of quetiapine XR could be problematic in the population of patients with a dual diagnosis. A post hoc analysis of the fatigue item of the FIQ (item 16) showed that the mean change was not statistically significantly greater in the quetiapine XR group compared with the placebo group (Ϫ1.1 and Ϫ0.8, respectively; P ϭ 0.143), suggesting that this adverse effect might be attributed to the known quetiapine XR effects of sedation and somnolence reported in depression treatment trials (26)(27)(28).…”

“…The vast majority of patients (Ͼ95%) were female, reflecting the higher prevalence of both fibromyalgia and depression in women in the general population and in clinical studies (6)(7)(8)20) The high mean body weight (Ͼ81 kg) at baseline is reflective of clinical samples of depressed patients with and those without comorbid fibromyalgia (8,27). The majority of patients were moderately to severely depressed, with a mean HAM-D score at baseline of 24.8; most had a recurrent course of illness, with nearly half (48%) reporting 2-5 lifetime episodes and a further 24% reporting Ն6 episodes.…”

“…Furthermore, one of its major metabolites, norquetiapine, has been shown to have a moderate affinity for the norepinephrine reuptake transporter and a 10-fold more potent effect than quetiapine at 5-HT 1A (25). This receptor-binding profile likely explains the demonstrated antidepressant efficacy of quetiapine XR as monotherapy for the treatment of both bipolar (26) and unipolar depression (27)(28)(29).…”

Lurasidone in the Long‐term Treatment of Patients With Bipolar Disorder: A 24‐week Open‐label Extension Study

“…Quetiapine monotherapy17 and adjunctive therapy (with lithium or divalproex)18, 19, 20 demonstrated significant efficacy in preventing recurrence of both manic and depressive episodes in bipolar populations. Limited data suggest that OFC might be effective as a long‐term therapy for prevention of depressive relapse,21, 22 although weight gain and metabolic effects may limit the utility of this treatment.…”