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July 20, 2004 — The risk of suicidal behavior is increased in the first month
after starting antidepressants, and is similar among users of four
antidepressant drugs, according to a study in the July 21 issue of The
Journal of the American Medical Association (JAMA).
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 10 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."
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.
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.
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