Dear Editor,
Recently, during a supervision session, we were looking at the tables for treatment of resistant depression. We thought that it would be an interesting exercise to compare and contrast the Maudsley guidelines from the 2005–2006 edition (Taylor, Reference Taylor, Paton and Kerwin2005–2006) with the most recent edition published in 2012 (Taylor etal. 2012).
We noted that that there was a significant change with respect to the advice when combining antidepressants. In the 2005–2006 edition, the combination of SSRI + mianserin or mirtazepine was deemed to have reasonable support in the literature. By 2012, the combination of SSRI or Venlafaxine + mianserin or mirtazepine was deemed to have excellent literature support.
To further explore this difference we checked the references. Interestingly, all three references cited in 2005 were cited in 2012; the only new reference in 2012 was the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) (McGrath, Reference McGrath, Stewart and Fava2006) study.
To suggest that the STAR*D provides excellent support for the above described combination of antidepressants merits comment. Hatcher (Reference Hatcher2008) expressed reservations about the clinical utility of the STAR*D study – describing it as a large and complicated trial where it was hard to draw clear conclusions from it. He concluded that it disappointingly only sheds a little light on how to manage depression in clinical practice. In a thorough review of combining antidepressants (incorporating the STAR*D study), Palaniyappan etal. (Reference Palaniyappan, Insole and Ferrier2009) caution that there is a weak evidence base for combinations of antidepressants. They, helpfully, draw attention to stronger data for options including switching to a drug of a different class, augmentation of antidepressants with psychotherapy, lithium or second generation antipsychotics. Additionally, they remind readers of the option of ECT. Finally the 2012 Maudsley Guidelines (Taylor etal. 2012) report that the STAR*D study to some extent confirmed the safety and (to a lesser extent) the efficacy of the combination of mirtazepine and venlafaxine.
We feel that the above evidence raises doubts about the recommendations regarding combinations of antidepressants. There is no doubt that this practice of combination is widely used. Should this widespread practice be more rigorously researched?
