Though the drug's label previously listed depression as a possible reaction, FDA strengthened the label warning in 1998 after reviewing cases with serious outcomes reported in the years after the drug was approved. The new labeling states that Accutane may cause depression and psychosis, and that in rare cases it may cause suicidal ideation (thoughts of suicide), suicide attempts, and suicide.
The label also advises providers that simply discontinuing the drug may not remedy any psychiatric problems and that further evaluation may be necessary. "In some cases, stopping Accutane alone may not be enough to relieve the mood changes," says Jonathan Wilkin, MD, director of CDER's division of dermatologic and dental drug products. "Psychiatric treatment may also be needed."
The relationship between Accutane and depression remains unproven, but some patients have reported that their depression subsided when they stopped the medication and came back when they resumed taking it. And some who have reported problems with depression while taking Accutane had no previous psychiatric history. FDA considers the number of reports of serious depression associated with Accutane high compared to other drugs in its database.
From 1982 to May 2000, FDA received reports of 37 U.S. Accutane patients who committed suicide, 24 while on the drug and 13 after stopping the drug. In addition to suicides, FDA received reports of 110 U.S. Accutane users hospitalized for depression, suicidal ideation, and suicide attempt during the same time period. As of May 2000, FDA had received reports of 284 Accutane users with non-hospitalized depression.
Several factors make it hard to definitively link depression with Accutane. Depression is a common problem, and some patients may be suffering from it before starting Accutane therapy. Additionally, some patients who reported depression with Accutane had previous courses of the drug without depression. Even so, it is recommended that doctors act as if Accutane could have psychiatric effects until there is more information, says FDA's Wilkin.
