Major Depressive Disorder sNDA Submission

The FDA approval of SEROQUEL XR for MDD was based on a supplemental new drug application (sNDA) comprising findings from two Phase III, placebo-controlled studies that assessed the efficacy and safety of once-daily treatment with SEROQUEL XR as adjunctive treatment in patients with MDD. Studies 6 and 7 were acute adjunctive therapy studies (with ongoing antidepressant therapy) involving 939 patients randomized (628 randomized to SEROQUEL XR) who had an inadequate response to their antidepressant therapy. Patients were on various antidepressants prior to study entry including SSRI's (paroxetine, fluoxetine, sertraline, escitalopram, or citalopram), SNRI's (duloxetine and venlafaxine), TCA (amitryptiline) and other (buproprion).

The primary endpoint in these studies was the change from baseline to end of treatment in the Montgomery-Asberg Depression Rating Scale(MADRS) total score. The recommended dose range of SEROQUEL XR in MDD is 150 to 300mg/day.

In both studies efficacy with SEROQUEL XR was superior to placebo, as assessed by the primary endpoints. SEROQUEL XR 300 mg once daily as adjunctive treatment to other antidepressant therapy was superior to antidepressant alone in reduction of MADRS total score in both trials. SEROQUEL XR 150 mg once daily as adjunctive treatment was superior to antidepressant therapy alone in reduction of MADRS total score in one trial. In these studies, the most commonly observed adverse reactions associated with the use of SEROQUEL XR (incidence of 5% or greater and at least twice that of placebo) were somnolence (150 mg: 37%, 300 mg: 43%), dry mouth (150 mg: 27%, 300 mg 40%), fatigue (150 mg: 14%, 300 mg: 11%) and constipation (150 mg only: 11%). The adverse events seen with SEROQUEL XR in these studies were generally consistent with the known profile of SEROQUEL XR in other indications.

SOURCE AstraZeneca