The U.S. Food and Drug Administration (FDA) Psychopharmacologic Drugs Advisory Committee (PDAC) conducted a review of the safety and efficacy of supplemental new drug applications (sNDA) for Seroquel XR (quetiapine fumarate) extended-release tablets proposed for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD).
The Advisory Committee concluded:
- Seroquel XR was shown to be effective in MDD as both monotherapy and adjunctive therapy, and shown to be effective in GAD as monotherapy.
- Seroquel XR was shown to be acceptably safe as an adjunctive treatment for MDD.
- Seroquel XR was not shown to be acceptably safe as a monotherapy for broad treatment for MDD.
- The committee was undecided as to whether Seroquel XR was shown to be acceptably safe in certain instances as a monotherapy treatment for MDD.
- Seroquel XR was not shown to be acceptably safe as a monotherapy for the treatment of GAD.
Howard Hutchinson, M.D., Chief Medical Officer of AstraZeneca, said: "We are pleased that the committee found Seroquel XR to be effective and acceptably safe for use as adjunctive therapy for the treatment of MDD. Although the committee recognized the effectiveness of Seroquel XR as monotherapy for MDD and GAD, they had concerns around the long-term safety profile in these new populations. We look forward to having further discussions with the FDA regarding both sNDAs."
The FDA frequently convenes advisory committee meetings to obtain independent expert guidance and recommendations on clinical matters. While the FDA is not required to follow this guidance, the agency usually takes the advice into consideration when rendering its final decisions on pending applications and other public health matters.
Seroquel XR, a once-daily, extended-release tablet formulation of Seroquel (quetiapine fumarate) tablets, was approved in the U.S. in 2007 for the acute and maintenance treatment of schizophrenia in adult patients and in October 2008 for the acute treatment of the depressive episodes associated with bipolar disorder, the manic and mixed episodes associated with bipolar I disorder, and the maintenance treatment of bipolar I disorder as adjunctive therapy to lithium or divalproex.
Important Safety Information for Seroquel XR and Seroquel
Seroquel XR is indicated for the treatment of acute depressive episodes associated with bipolar disorder, acute manic or mixed episodes associated with bipolar I disorder as monotherapy and as an adjunct to lithium or divalproex; maintenance treatment of bipolar I disorder as adjunct therapy to lithium or divalproex, and acute and maintenance treatment of schizophrenia. Seroquel is indicated for the treatment of depressive episodes in bipolar disorder; acute manic episodes in bipolar I disorder, as either monotherapy or adjunct therapy to lithium or divalproex; maintenance treatment of bipolar I disorder as adjunct therapy to lithium or divalproex; and schizophrenia. Patients should be periodically reassessed to determine the need for continued treatment and the appropriate dose.
Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk (1.6 to 1.7 times) of death, compared to placebo (4.5% vs. 2.6%, respectively). Seroquel XR and Seroquel are not approved for the treatment of patients with dementia-related psychosis. (See Boxed Warning.)
Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies of major depressive disorder and other psychiatric disorders. Patients of all ages started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Seroquel XR and Seroquel are not approved for use in patients under the age of 18 years. (See Boxed Warning.)
Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics, including quetiapine. The relationship of atypical use and glucose abnormalities is complicated by the possibility of increased risk of diabetes in the schizophrenic population and the increasing incidence of diabetes in the general population. However, epidemiological studies suggest an increased risk of treatment-emergent, hyperglycemia-related adverse reactions in patients treated with atypical antipsychotics. Patients starting treatment with atypical antipsychotics who have or are at risk for diabetes should undergo fasting blood glucose testing at the beginning of and periodically during treatment. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing.
In long-term clinical trials of quetiapine, hyperglycemia (fasting glucose Greater Than or Equal To 126 mg/dL) was observed in 10.7% of patients receiving quetiapine (mean exposure 213 days) vs. 4.6% in patients receiving placebo (mean exposure 152 days).
Clinically significant increases in cholesterol (7%-16% for quetiapine vs. 3%-9% for placebo) and triglycerides (8%-23% for quetiapine vs. 5%-16% for placebo) have been observed in clinical trials.
The proportion of patients in clinical trials meeting a weight gain criterion of Greater Than or Equal To 7% of body weight was 5%-23% for quetiapine vs. 0%-7% for placebo.