According to background information in the article, considerable public attention recently has focused on the relation between use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and suicidal ideation (having thoughts of suicide or of taking action to end one's own life) and suicidal behaviors. SSRIs are antidepressant drugs that work by making available more serotonin, a chemical in the brain that is thought to play a key role in depression and anxiety. The use of antidepressant drugs among teenagers has been of particular concern.
Hershel Jick, M.D., and colleagues with the Boston Collaborative Drug Surveillance Program, Boston University, estimated the relative risks of non-fatal suicidal behavior in patients in the United Kingdom starting treatment with the SSRIs fluoxetine and paroxetine and another antidepressant, amitriptyline--compared with patients starting treatment with a fourth drug, dothiepin, that is not available in the U.S. Amtriptyline and dothiepin belong to a class of drugs known as tricyclic antidepressants. 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 write. "The risk of suicidal behavior is increased in the first month after starting antidepressants, especially during the first one to nine days," they report. "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 ten to 19 years," the authors write.
"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 conclude. "The available information on young people aged ten through 19 years is limited, however, and some important difference in effect cannot be ruled out based on this study." (JAMA. 2004; 292:338-343. Available post-embargo at JAMA.com)
Editor's Note: Funding for this study was from general funds available to the Boston Collaborative Drug Surveillance Program. The authors did briefly consult on the principles of study design for a possible company study on antidepressants and suicidal behavior with representatives of GlaxoSmithKline, the manufacturer of paroxetine. The Boston Collaborative Drug Surveillance Program received funding for consultation. The company has no knowledge of the study design, results, or interpretation that the authors are reporting.
Media Advisory: To contact Hershel Jick, M.D., call Julianne Lamay at 617/638-8491. To contact editorialist Simon Wessely, M.Sc., M.D., F.R.C.Psych., F.Med.Sci., email s.wessely@iop.kcl.ac.uk.
EDITORIAL: SUICIDE RISK AND THE SSRIS
In an accompanying editorial, Simon Wessely, M.D., of the Institute of Psychiatry, London, writes, "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 continues: "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 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," Dr. Wessely writes. "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 concludes.
(JAMA. 2004; 292:379-381. Available post-embargo at JAMA.com)
Editor's Note: Dr. Wessely has received financial support from Pierre Fabry Pharmaceuticals and from Eli Lilly and Co. to attend academic meeting and for speaking engagements. For More Information: Contact the JAMA/Archives Media Relations Department at 312-464-JAMA (5262) or email: mediarelations@jama-archives.org.
Journal
JAMA