Thomas Laughren, M.D.
Director, Division of Psychiatry Products
Food and Drug Administration / CDER
10903 New Hampshire Ave
WO Building 22, Room 4114
Silver Spring, MD 20993
Dear Dr. Laughren,
Yesterday, the Psychopharmacologic Drugs Advisory Committee met to discuss Seroquel XR for use in Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD), because of the FDA’s concern over the long-term toxicities of this drug. The committee voted unanimously that Seroquel is unsafe for use as first-line therapy in either MDD or GAD. The committee also voted that Seroquel is unsafe for use in “certain instances,” rejecting any role for use as second- or third-line monotherapy. However, the committee did vote that Seroquel is safe for use as adjunctive therapy in MDD only. We agree that Seroquel is unsafe for use as monotherapy for MDD or GAD, under any circumstance. If the FDA expands the use of Seroquel to include the indication of adjunctive therapy for MDD, we recommend stringent labeling, including a boxed warning clearly stating that Seroquel is contraindicated as monotherapy for MDD.
From over a decade of use in schizophrenia and bipolar disorder, it is known that Seroquel causes: (1) heavy sedation; (2) tardive dyskinesia – an irreversible, disabling movement disorder; and (3) metabolic derangements including weight gain, adverse effects on lipids, and hyperglycemia, all of which may confer cardiovascular risk. A large retrospective cohort study recently published in the New England Journal of Medicine also suggests that Seroquel and other atypical antipsychotics are associated with a large increase in risk of sudden cardiac death. Overall, Seroquel is less tolerable and far less safe than existing approved therapies for MDD or GAD.
Despite these adverse effects, rampant off-label and inappropriate prescribing of Seroquel and other atypical antipsychotics already occurs, especially in vulnerable populations. Elderly patients are increasingly placed on atypical antipsychotics to treat insomnia or delirium associated with dementia. There is little or no evidence of benefit in these settings, but the potential for harm is substantial, including heavy sedation and even an increased risk of death. In addition, recreational use of Seroquel is on the rise. Therefore, expanding the use of Seroquel to include common disorders such as MDD and GAD would open the floodgates for even greater inappropriate use, and increase the potential for diversion and abuse.
If there were no effective treatments for MDD and GAD, or if Seroquel was more effective than existing therapies, then perhaps its wide range of toxicities might be tolerated. However, this is not the case. Therefore, we strongly urge you to heed the recommendations of the advisory committee and not expand the label for Seroquel to include use as monotherapy in MDD or GAD. If Seroquel is approved for use as adjunctive therapy in MDD, a boxed warning that clearly prohibits its use as monotherapy is needed, given the potential for harm with this drug.
James Floyd, M.D.
Researcher, Public Citizen
Sidney Wolfe, M.D.
Acting President, Public Citizen
cc: Robert Temple, M.D., Janet Woodcock, M.D., Joshua Sharfstein, M.D.