Quetiapine: A Review of its Use in the Management of Bipolar Depression CNS Drugs, 04/24/2012

Sanford M et al. – Quetiapine and quetiapine extended–release are valuable additions to the first–line treatments for bipolar depression.

• The efficacy and tolerability of quetiapine was evaluated in five 8-week, randomized, double-blind, placebo-controlled, multicentre or multinational trials in patients with a major depressive episode (MDE) associated with bipolar disorder.
• Across trials, monotherapy with oral quetiapine 300 or 600 mg/day (or quetiapine XR 300 mg/day) produced significantly greater improvements than placebo in depressive symptoms (primary endpoint), according to the change in the Montgomery-Asberg Depression Rating Scale total score.
• In general, quetiapine and quetiapine XR were also associated with significantly higher MDE response and remission rates than placebo.
• Across trials, quetiapine and quetiapine XR produced significantly greater improvements in global severity of illness scores than placebo, according to changes in the Clinical Global Impressions scale score.
• There were no differences in treatment outcomes between quetiapine 300 mg/day and 600 mg/day dosage groups.

• Patients with bipolar depression who responded to quetiapine during two 8-week acute treatment trials also benefited from continuing quetiapine therapy for up to 52 weeks.
• Compared with quetiapine responders randomized to placebo, quetiapine responders who continued quetiapine 300 or 600 mg/day had a significantly reduced risk of recurrence of any mood events and of depression mood events, but not of hypomanic/manic events.
• In a randomized, double-blind, placebo-controlled trial, quetiapine maintenance therapy for up to 104 weeks was more efficacious than placebo or lithium in prolonging the time to recurrence of any mood event (primary endpoint).
• Patients in this trial had bipolar I disorder with mania, depression or a mixed episode as the index episode, and the trial included only patients who were responsive to acute phase quetiapine, which may have introduced a positive bias in favour of quetiapine over lithium during maintenance therapy.
• Quetiapine 300 or 600 mg/day and quetiapine XR 300 mg/day was generally well tolerated in patients with bipolar depression, with most treatment-emergent adverse events being of mild to moderate severity.
• The most frequent adverse events occurring during the acute treatment phase were dry mouth, sedation, somnolence, dizziness (quetiapine and quetiapine XR), constipation (quetiapine) and increased appetite (quetiapine XR).
• Extrapyramidal symptoms (EPS) occurred across quetiapine and placebo groups, but there were no significant differences between quetiapine and placebo recipients on objective measures of EPS and akathisia.
• In some trials, quetiapine recipients experienced significantly greater weight gain than placebo recipients.
• Across trials, some quetiapine recipients had clinically relevant increases in blood glucose or lipid parameters, although these also occurred in patients from other treatment groups.
• The clinical significance of these changes is uncertain.