Shortcomings revealed in trials of antidepressants in children
A review of clinical trials that evaluated the safety and efficacy of antidepressants in children has found shortcomings in the way the trials were conducted and in the way investigators reported the results.
Jon Jureidini, Women’s and Children’s Hospital, North Adelaide,
Australia, and colleagues checked the quality of methods and reporting
of seven published trials of newer antidepressants in children.
They say that investigators’ conclusions exaggerated the benefits of drug
treatment. In the six placebo-controlled trials, claims for effectiveness were
based entirely on ratings by doctors. Indeed, none of the measures relying on
patient or carer reports showed advantages for the antidepressants compared with
placebo. The researchers also point out that improvements seen among patients
given placebo were large, calling into question the clinical significance of
the drugs’ effects.
In terms of adverse events, the researchers say they would expect investigators
to draw attention to them, given that trial follow up periods were short and
numbers of serious adverse effects would be expected to be small. This was not
the case, however.
In one trial, drug treatment resulted in 11 serious adverse events among 93 patients.
This compared with two events among the 87 patients given placebo. The difference
was significant but the investigators did not present a statistical analysis
of the data. And in spite of the difference in serious adverse events the investigators
concluded that the drug being tested — paroxetine — was generally
well tolerated.
Reporting of data from another study
revealed similar shortcomings. Among 189 patients treated with sertraline, 17
(9 per cent) withdrew because of adverse events. This compared with five withdrawals
from the 184 patients given placebo. Again, no analysis of this outcome was published
and the investigators concluded that the drug was well tolerated by children
and adolescents.
Other examples of methodological and reporting discrepancies are cited by the
researchers, who conclude: “In discussing their own data, the authors of
all the four larger studies have exaggerated the benefits, downplayed the harms,
or both.”
They add: “We are concerned that biased reporting and overconfident recommendations
in treatment guidelines may mislead doctors, patients and families.”
The review is published in the BMJ (2004;328:879). |
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