Efficacy of Quetiapine Monotherapy in Bipolar I and II Depression

Abstract

This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P <or= 0.001 vs. placebo). Therapeutic effect sizes at Week 8 were 0.61 and 0.54 for quetiapine 300 and 600 mg/d, respectively. Improvements in mean HAM-D scores were also significantly greater with both quetiapine doses than with placebo (P < 0.001) as early as Week 1 and throughout the study. The MADRS response and remission rates were also significantly greater in both quetiapine dose groups compared with placebo. Improvements in primary and secondary outcomes were observed with both 300 and 600 mg/d quetiapine without major differences between the doses. Common adverse events included dry mouth, sedation, somnolence, dizziness, and constipation. The incidence of treatment-emergent mania or hypomania was lower with quetiapine treatment than placebo. This study demonstrates that quetiapine monotherapy is an effective and well-tolerated treatment for depressive episodes in bipolar disorder, confirming the results observed from a previous study (BipOLar DEpRession [BOLDER] I).

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…Pooled analyses of five identically designed trials demonstrated that quetiapine was superior to placebo, and moreover was equally effective for acute depression in BDI and BDII 243, 437. The latter finding must be reconciled with the fact that quetiapine beat placebo in only three of the five individual trials in patients with BDII, compared to all five in patients with BDI 253, 290, 438, 439, 440. This is probably because the smaller sample of BDII patients—only about half as many patients with BDII as BDI were enrolled in each of the trials—provided less statistical power for BDII.…”

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

“…Among atypical antipsychotics, quetiapine monotherapy,11, 12 and olanzapine in combination with fluoxetine (OFC),13 have demonstrated efficacy in the acute treatment of bipolar depression, whereas aripiprazole monotherapy,14 and ziprasidone monotherapy15 and adjunctive therapy (with lithium or divalproex)16 were not significantly different from placebo in controlled acute trials. 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.…”

How can we classify &ldquo;mood stabilizers&rdquo; with different properties?

“…The NICE [16] and CANMAT [11] guidelines now recommend QTP as the first-line drug, especially for the more severe pathophysiology of acute mania, due to its rapid and potent antimanic effects. Meanwhile, the efficacy of QTP monotherapy in acute bipolar depression has been consistently confirmed by such double-blind, placebo-controlled studies as BOLDER (BipOLar DEpRession) I/II [8,20] and EMBOLDEN (Efficacy of Monotherapy SEROQUEL in BipOLar DEpressioN) I/II [17,21]. The latter EMBOLDEN studies also examined the efficacy of QTP monotherapy in relapse prevention for bipolar disorders, and the results suggested that the preventive effect of QTP monotherapy is superior to that of placebo for both manic and depressive recurrence, and is superior to that of Li for depressive recurrence [11], and that the efficacy of Li or VPA for relapse prevention of any mood episode is clearly augmented by QTP coadministration [10,22].…”

“…In fact, QTP, OLZ, ARI, RIS and paliperidone are known to have potent effects against acute mania as well as schizophrenia [6]. As for the treatment of acute bipolar depression, the efficacy of QTP monotherapy has been established [8], and OLZ exhibits similar efficacy when combined with fluoxetine (OLZ-fluoxetine combination: OFC) [9], both of which have been already approved by the FDA. In addition, it has been also confirmed that QTP [10,11], OLZ [7,11], ARI [5] and long-acting injection (LAI) of RIS [11] …”