Risk for suicidal behavior is increased in the first month of antidepressant therapy and appears to be similar for selective serotonin reuptake inhibitors and tricyclic antidepressants, according to an article in the July 21st issue of The Journal of the American Medical Association..


Hershel Jick, MD, and his American colleagues estimated the relative risks of non-fatal suicidal behavior in patients in the United Kingdom starting treatment with fluoxetine, paroxetine, or amitriptyline compared with risk for the tricyclic dothiepin. Participants could have used only one of the antidepressants, and had to have received at least one prescription for the drug within 90 days before their index date (the date of suicidal behavior or ideation for cases, and the same date for matched controls).

“The risk of suicidal behavior after starting antidepressant treatment is similar among users of amitriptyline, fluoxetine, and paroxetine compared with the risk among users of dothiepin,” the authors wrote. “The risk of suicidal behavior is increased in the first month after starting antidepressants, especially during the first one to nine days. We think the most likely explanation for this finding is that antidepressant treatment may not be immediately effective, so there is a higher risk of suicidal behavior in patients newly diagnosed and treated than in those who have been treated for a longer time.”

“Based on limited information, we also conclude that there is no substantial difference in effect of the four drugs on people aged 10 to 19 years,” the authors added.

“Given the careful control of potential confounding variables, including age, sex, calendar time, and duration of treatment prior to suicidal behavior, this study provides evidence that the risk of suicidal behavior is not substantially different among patients starting treatment with amitriptyline, fluoxetine, or paroxetine than among patients starting treatment with dothiepin,” they concluded. “The available information on young people aged 10 through 19 years is limited, however, and some important difference in effect cannot be ruled out based on this study.”

In an accompanying editorial, Simon Wessely, MD, wrote “The results [from Jick et al] confirm that antidepressant prescription is indeed associated with suicidal behavior, and strongly so. This simply means that antidepressants are being prescribed for the right indication, and that they do not immediately eliminate suicide risk. That we knew.”

He continued, “But the hypothesis being tested is that over and above the known association of antidepressant prescribing and suicidal behavior (in which the confounder is the presence of depressive disorder), there is also a specific link in which one class of antidepressants, the selective serotonin reuptake inhibitors (SSRIs), increases that risk further. The results do not offer much support for the hypothesis.”

“However, the authors appropriately caution against overinterpreting this borderline result,” Wessely noted. “Most UK general practitioners are now aware that the older tricyclic drugs are more dangerous in overdose, and it remains plausible that there is a tendency to prescribe the newer SSRIs for patients about whom the physician has more concerns about suicidal risk. Only a small such bias could cause the observed results. Moreover, there was no evidence for the alleged withdrawal phenomenon, which is another of the concerns that have been raised about the SSRIs. Stopping medication did not lead to an increased risk, as postulated by some.”

“Whatever decision clinicians reach, careful monitoring of adolescents (for activation, agitation, and suicidal ideation) prescribed any antidepressant remains essential,” Dr. Wessely concluded.