Independent studies are needed before causality is established

EDITOR —Lindberg et al suggested that the use of calcium channel blockers increases the risk of suicide.1 Methodological problems, however, render that conclusion uncertain. In a cross sectional ecological study they found a weak but significant correlation between rates of suicide and use of calcium channel blockers, expressed as numbers of defined daily doses dispensed by pharmacies in 152 municipalities in Sweden. The defined daily dose is, however, a technical unit for studies of use of drugs2; defined daily doses might differ twofold or more from the daily doses actually prescribed. Therefore, when used for other purposes, such as an estimate of individuals at risk (as in Lindberg et al's paper), methods based on the defined daily dose require validation.3

The authors also carried out a historical cohort study of patients with an index prescription of an antihypertensive drug. They found that “five users of calcium channel blockers (three men and two women, one with uncertain intent) and four non-users (three men and one women, none with uncertain intent) committed suicide” within seven years after they bought the index drug in 1988 or 1989. A minimum requirement for applying statistics on the outcome in nine individuals is to validate exposure as well as outcome. One misclassification in this study would mean that the difference was no longer significant. One of the “suicides” in the calcium channel blocker cohort was not even a certain suicide but an undetermined unnatural death. The remaining eight cases of alleged suicide were not validated against death certificates or medical records. It is not known whether these nine patients were taking an antihypertensive drug at the time of death, whether they were depressed, etc. Potential confounders, such as the severity of hypertension, comorbidity, concomitant drug treatment, and history of depression or use …