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The potential limitations of observational research must be considered in interpreting the results of this study. Because this study only included cases with non-fatal MI, a false-negative association could be created if users of SSRIs were more likely to develop sudden death after an MI. This bias is unlikely, because SSRIs do not have arrhythmogenic properties.7, 12 Unlike tricyclic antidepressants, SSRIs do not have class I antiarrhythmic properties, a characteristic associated with increased mortality post-MI.35 In addition, SSRIs do not alter intraventricular conduction times or QT intervals.6, 7 A low participation rate could have created a false association if nonparticipant cases were more likely to use SSRIs for treatment of depression. However, nonparticipant cases were less likely to have private medical insurance and perhaps therefore less likely to have received an SSRI. This would, if anything, bias the results toward the null. A false association could also have been created if nonparticipant control subjects were less likely to use SSRIs compared with participants. However, the 4.35% exposure rate seen in our control group is similar to the 4.05% prevalence of SSRI use in the general population during the same time period.36 In addition, even if SSRI use among the potentially eligible control subjects who did not participate was one third of the participant's, there would still be a significant association between SSRIs and reduced MI risk OR 0.56, P 0.05 ; . Differential recall of SSRI use could create a false inverse association if control subjects were more likely than cases to accurately report SSRI exposure. Although the OR of 0.5 for users of non-SSRI antidepressants could reflect differential recall, it also may be attributable to chance or bias, as previously discussed. In addition, the fact that anxiolytic use was not associated with MI suggests that differential recall of medications was unlikely to have produced our results. Uncontrolled confounding is another potential limitation of our study. If SSRI users are a low risk group because of other unmeasured unique characteristics, there would be a false association between SSRIs and lower risk for MI. Because SSRIs require a doctor's prescription as well as adequate follow-up to monitor progress, it also is possible that better medical attention and treatment of modifiable risk factors for MI could account for the protective effect seen. However, SSRI users had more traditional risk factors for MI, and adjustment for all known potential risk factors except sex ; , including variables related to access to medical care, strengthened rather than weakened the inverse association between SSRI use and MI. In addition, use of anxiolytics, which also require a prescription and medical follow-up, was not associated with MI protection, making this bias unlikely. Finally, confounding by indication ie, if SSRIs were used for a condition that is itself associated with lower MI risk ; could not explain these results, because the indication for SSRIs, depression, should, if anything, increase the risk of MI.1, 2 This would bias the results toward a falsely harmful effect of SSRIs. Because we only recorded current use within the index week, some SSRI users may not have received the duration of.
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