FDA's Linking of Newer Antidepressants to Suicidality Questioned

June 3, 2007
Bruce Sylvester

Internal Medicine World Report, February 2006, Volume 0, Issue 0

FDA warnings issued in the past about the link to suicidality with newer antidepressants may be un?warranted and could discourage physicians and patients from using effective treatment, investigators found in a 10-year study (Am J Psychiatry. 2006;163:41-47).

"The new antidepressants don't appear to be more risky than the older ones. If anything, the risk of suicide attempt is lower with the newer medications," lead investigator Gregory Simon, MD, MPH, of the Center for Health Studies, Group Health Cooperative, Seattle, told IMWR.

Invest?igators examined data from 65,103 patients enrolled in a large health plan who filled prescriptions for antidepressants between 1992 and 2003.

Suicide attempts among adults fell by 60% during the month after treatment initiation and decreased further in the subsequent 5 months.

A higher rate of suicide attempts was reported among adolescents than among adults during the first 6 months of therapy. Suicidality was highest in the month before treatment and declined by about 60% after treatment began. "Contrary to conventional wisdom, the period after starting antidepressant medication is not especially risky. Compared with the month before starting antidepressant medication, risk of suicide attempt goes down in the month after," Dr Simon said.

These findings challenge the FDA's warnings on 10 newer antidepressants: bupropion (Wellbutrin), citalopram (Celexa), fluoxetine (Prozac), fluvoxamine, mirtazapine (Remeron), nefazodone, paroxetine (Paxil), sertraline (Zoloft), escitalopram (Lexapro), and venlafa-xine (Effexor).

"When the 10 newer antidepressants included in the FDA advisory were compared with older drugs, an increase in risk after starting treatment was seen only for the older drugs," the investigators noted. The older agents included in this study and not included in the FDA advisory were tricyclic antidepressants and trazodone (Desyrel).

Taking aim directly at the FDA advisory, the investigators concluded that "closer monitoring of antidepressant treatment is clearly needed, but warnings regarding suicide precipitated by antidepressants may do more to discourage effective treatment than to improve the quality of follow-up care."

Darrel Regier, MD, director of research at the American Psychiatric Association, told IMWR that this study appears at a time when the FDA continues to investigate reports of suicidality among adults taking antidepressants. "Dr Simon's research provides solid evidence that confirms a key lesson of clinical practice?that treatment with antidepressant medication significantly reduces the risk of self-harm that is a core symptom of untreated depression."

Dr Regier added that there is a possibility that vulnerable individuals will have increased suicidality during antidepressant treatment.