Pharmacological heterogeneity limits antidepressant study

EDITOR—MacGillivray et al potentially make a huge contribution to the understanding of the relative utility of selective serotonin reuptake inhibitors and older antidepressants in the treatment of depression in primary care.1 However, the usefulness of their meta-analysis is limited by the original data, as is so often the case.

These results are very difficult to interpret, not least because the comparitors used in the key studies are pharmacologically heterogeneous. Two studies, including one of the key three crucial studies providing data in an unambiguous format, used mianserin as a comparitor. Mianserin is a tetracyclic, not a tricyclic as the paper's title might imply. It is not a potent reuptake inhibitor but a potent and thus sedative anti-histamine. A third study used lofepramine as a comparitor, a more modern tricyclic with a much more benign anticholinergic side effect profile than its older cousins, which have an adverse event rate similar to the selective serotonin reuptake inhibitors.2

Two of the three studies providing unambiguous data for the efficacy analysis were of paroxetine against amitriptyline. Paroxetine may be considered to be an atypical selective serotonin reuptake inhibitor in that is has some adrenergic reuptake inhibition and anticholinergic properties. Pharmacologically its profile lies between the more selective selective serotonin reuptake inhibitors and the classic tricyclics, as does lofepramine.3

As an underlying principle of meta-analysis is homogeneity of the material, it is no surprise that a clear answer does not emerge from this work, given the pharmacological heterogeneity.