Antidepressants and suicide risk: issues of chemical and behavioral toxicity

Recent reports have described several patients who experienced suicidal preoccupation while being treated with antidepressant drugs. This phenomenon has been interpreted as antidepressant-induced suicidal behavior. The association of antidepressant medication with suicide was noted early in their clinical use. Antidepressants have been a common cause of suicide when taken in overdose. Epidemiologic studies have reported that antidepressants differ from one another in the frequency with which they are associated with suicide by overdose. This differential association of antidepressants with suicide might support the possibility that certain agents may induce suicidal behavior. However, it seems that the frequency with which an antidepressant is related to suicide by overdose is correlated with each compound's inherent toxicity. Reported cases of emergence of suicidal preoccupation during fluoxetine treatment have raised the possibility that serotonergic drugs may induce this destructive behavior. Although this hypothesis rests on only a few reported cases, large-scale clinical trials of serotonin uptake inhibitors such as fluoxetine, paroxetine, and sertraline do not support it. Thus, the decreased toxicity of newer antidepressants such as fluoxetine and other selective serotonergic drugs makes them an attractive choice for treatment of depressed patients who are at risk for suicide.