The FDA issued a “black-box” warning for antidepressant labeling in 2004 because of concerns about a possible link between suicide and antidepressants in patients younger than age 18. Close to two years later, some community mental health providers say that family members’ and patients’ attitudes toward antidepressants have been affected by the FDA's move, but new research suggests the connection between antidepressant use and increased suicidality is not as strong as the FDA suspected—if it exists at all.
Karen Rhea, MD
“Psychiatrists and nurse practitioners at our organization believe that the black-box warning and the additional focus with parents on risk potential have decreased parental acceptance of these medications,” says Karen Rhea, MD, a child and adolescent psychiatrist and vice-president for medical services for Centerstone, a large community mental health provider organization in Tennessee.
Alexander Fariborzian, MD, medical director of Meridian Behavioral Healthcare in Gainesville, Florida, which serves 11 counties in North Florida, says the organization began issuing “advisories” to parents after the black-box warning went into effect. “Parents are provided with a copy of the advisory, and they are educated on new information in the black-box warning,” says Dr. Fariborzian. “Then they have to sign the advisory” to show consent for their child to receive medication, he says.
New Study Findings
Yet a new, large study indicates that the risk of suicide is decreased significantly in patients taking antidepressants.1Investigators assessed 82,285 treatment episodes in more than 65,000 adult and pediatric patients ranging in age from 5 to 105 who filled prescriptions for antidepressants while enrolled in a large health plan from 1992 to 2003. The mean age of the subjects was 44, and 5,107 episodes (6.2%) were among patients younger than age 18.
The researchers evaluated ten newer antidepressants, such as SSRIs and bupropion (Wellbutrin), and compared them with older antidepressants, such as tricyclics and trazodone. In a month-by-month analysis of newer antidepressants, suicide attempt rates were highest in the month before starting treatment, and risk during the first month of treatment was not significantly higher than in months two through six. Among patients on older drugs, the risk was highest during the first month of treatment, and that risk was significantly higher than in months two through six.
The risk of a suicide attempt was slightly higher in youths than in adults on antidepressant therapy (314 per 100,000 versus 78 per 100,000, respectively), but the study's lead author, Gregory Simon, MD, MPH, psychiatrist and researcher at the Group Health Cooperative in Seattle, says that suicide attempts among adolescents tend to be intrinsically higher than among adults. In addition, the risk of death by suicide was not significantly higher among adults and adolescents during the month after starting medication than during subsequent months.
“Our finding that suicide risk goes down after starting medication is true in adolescents, as well as adults,” Dr. Simon notes. “Our study shows that the risk of serious suicide attempt or suicide death after starting antidepressants is, fortunately, low. Contrary to conventional wisdom, the period after starting medication is not an especially high-risk period. In fact, risk goes down after starting medication.”
The black-box warning on antidepressant product labeling, however, states that “antidepressants increase the risk of suicidal thinking and behavior… in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders,” and that youth should be “observed closely for clinical worsening, suicidality, or unusual changes in behavior.”2
The FDA's black-box warning is aimed at children and adolescents, but this past July the FDA issued a public health advisory on the use of antidepressants by adults, recommending they be “watched closely for worsening of depression and for increased suicidal thinking or behavior,” and that adults whose symptoms worsen while on antidepressants should be evaluated by their healthcare professional.3
The FDA developed the warning for youths based on a combined analysis of 24 short-term (up to four months) placebo-controlled trials of nine antidepressants that included more than 4,400 pediatric patients. The FDA reported in a public health advisory on October 15, 2004, that the average risk of suicidality was 4% in the studies reviewed, which was twice the placebo's risk. No actual suicides occurred during the trials.4
Some experts have criticized the FDA's rationale for requiring the black-box warning. One published analysis notes that not only did no suicides occur in the 4,400 patients, but that the definition of “suicidality” was unclear and that the data collected were not prospective.5 (A prospective study is specifically designed to look for outcomes and compares those outcomes with other factors such as suspected risk.) Another review claims that patients in drug trials (the type of patients the FDA studied) are not representative of typical patients in routine clinical practice.6