An important methodology problem
David Gunnell et al’s study conclusion of a trend towards increased
risk of suicide and self harm caused by SSRIs should be accepted very
seriously, given that it based on data from placebo-controlled trials.
Their conclusions could become substantially stronger, if they have
discussed a methodological problem of clinical trials. This problem is the
discrepancy between the efficacy and safety that an experimental drug
demonstrates in clinical trials and its beneficial and adverse effects in
daily clinical practice. One possible explanation for this discrepancy is
that the service context of clinical trials is essentially different from
routine psychiatric care. The main difference is the selection of patients
characterized by predominance of specific types of symptoms, and the
application of multiple exclusion criteria in clinical trials (in this
case, any manifestation of suicidality). In addition, only the
experimental compound in a restrictively defined dosing regimen is
administered in a trial, whereas polypharmacy and a broad dosage range are
prevalent in everyday practice. As a result, clinical trials recruit
patients who tend to be in a minority, while findings and conclusions have
been generalized to entire populations of patients with similar diagnoses.
These considerations always must be taken into account when we interpret
data obtained from clinical trials.
Gunnell D, Saperia J, Ashby D. Selective serotonin reuptake
inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company
data from placebo controlled, randomized controlled trials submitted to
the MHRA's safety review. BMJ. 2005 Feb 19;330(7488):385.
Competing interests: No competing interests