Do selective serotonin reuptake inhibitors cause suicide?

Editor—Gunnell et al’s report on suicide risk with selective serotonin reuptake inhibitors (SSRIs) raises several issues. Firstly, clinicians have observed that the first weeks of treatment of severe depression with an antidepressant are accompanied by a higher risk of suicide because of a drug induced motor disinhibition that is not yet accompanied by mood improvement. Secondly, the authors’ finding of a trend towards a protective effect of SSRIs against suicidal thoughts (odds ratio 0.77) compared with a trend towards an increased risk of self harm (odds ratio 1.57) is paradoxical. More surprising is the heterogeneity of results among SSRIs. Why would sertraline show a protective effect for suicidal thoughts and simultaneously increase the risk of self harm? The risk difference between citalopram and its active S-enantiomere, escitalopram, is also strange. No strong biological rationale can explain such heterogeneity among drugs with the same mechanism of action. Thirdly, the authors mention that the Medicine and Healthcare products Regulatory Agency found little evidence for a risk difference between SSRIs and the other antidepressants. The two accompanying papers show that the suicidal risk seems similar for serotoninergic and tricyclic antidepressants. 4 The risk of suicide must be assessed for the whole class of antidepressants. The next stage would be to measure the risk of suicide according to the time since starting an antidepressant. Initially, the risks are higher than the benefits. To confirm old clinical observations by evidence based methods would be interesting and useful.