FDA Approves Extended-Release Quetiapine as Add-On Treatment of Depression

Yael Waknine

December 07, 2009

December 7, 2009 — The US Food and Drug Administration (FDA) has approved a new indication for quetiapine fumarate extended-release tablets (Seroquel XR, AstraZeneca Pharmaceuticals, LP), allowing their once-daily use as adjunctive treatment to antidepressants in adults with major depressive disorder (MDD). The recommended dose range is 150 to 300 mg/day.

"Many people with [MDD], despite being treated with currently approved medications, continue to experience depressive symptoms," said Richard Weisler, MD, adjunct professor of psychiatry at the University of North Carolina School of Medicine, Chapel Hill, and adjunct associate professor at Duke University Medical Center, Durham, North Carolina, in a company news release. "Seroquel XR may provide another effective treatment option for the depressive symptoms associated with MDD as adjunctive treatment to antidepressants."

The FDA's action was based on data from 2 phase 3 clinical studies of 939 patients with refractory MDD, showing that the addition of extended-release quetiapine to antidepressant therapy yielded significantly greater reductions in Montgomerey-Asberg Depression Rating Scale total score.

Adverse events most commonly reported in study patients receiving quetiapine were consistent with the drug's profile and included somnolence (150 mg/day, 37%; 300 mg/day, 43%), dry mouth (150 mg/day, 27%; 300 mg/day, 40%), fatigue (150 mg/day, 300 mg/day, 14%; 11%), and constipation (150 mg only, 11%).

Other potential adverse events related to use of the atypical antipsychotic may include rapid weight gain, tardive dyskinesia, suicidal thinking and behavior, neuroleptic malignant syndrome, hyperglycemia, increased cholesterol levels, leukopenia, neutropenia, and agranulocytosis.

Because of these and other risks, the FDA is requiring implementation of a risk evaluation and mitigation strategy for all quetiapine indications. The program requires a medication guide and periodic assessments that include a survey of patients' understanding regarding the potential adverse effects of treatment.

Quetiapine extended-release tablets previously were approved for the treatment of schizophrenia, depressive episodes of bipolar disorder, manic or mixed episodes of bipolar disorder as either monotherapy or adjunct therapy to lithium or divalproex, and the maintenance treatment of bipolar disorder as adjunct therapy to lithium or divalproex.

Other indications currently under FDA review include acute monotherapy and maintenance monotherapy for the treatment of MDD in adult patients.