Letters
Mental health Pharmacology
Volume 187 - Issue 3

Beyond the evidence: is there a place for antidepressant combinations in the pharmacotherapy of depression?

Authors:  Murray J Walters, Alston M Unwin and Sean B Gills

Med J Aust 2007; 187 (3): 198-200. || doi: 10.5694/j.1326-5377.2007.tb01193.x
Published online: 6 August 2007
Download PDF (483 KB)
Share: Share on Blue Sky Share on Facebook Share on LinkedIn Share by email

To the Editor: Keks et al make a number of important points about the place of combination antidepressant strategies in the pharmacotherapy of depression.1 However, it is important for readers to note that the vigorous repudiation of combination treatments is a peculiarly Australian preoccupation. Our colleagues in Europe and North America are not nearly so troubled.

Combination antidepressant treatments are widely used by specialists. A recent survey of Australian doctors working in psychiatry reported that 79% of respondents had used combination antidepressants and that 75% believed that general practitioners should be given information on their use.2

There is emerging evidence for the use of combination antidepressant strategies — from case series, open clinical trials, and randomised controlled trials (RCTs). The largest summation of the data is a meta-analysis which found that combination antidepressant treatment produced a 62% response rate when monotherapy had failed.3 Although this finding alone cannot be convincing because of the acknowledged lack of large sample RCTs, it is quite another matter to decry combination prescribing as clinically unsound based only on the history of augmentation treatments such as lithium and, to a lesser extent, thyroid hormone treatment when, anecdotally, they provide such clinically disappointing results.

It is not unreasonable to assert the primacy of good clinical reasoning, including sensible prescribing of combination antidepressants, over rigid adherence to evidenced-based algorithms. This sort of thinking is allowable because the evidence base for the treatment of depression is poor. Meaningful guidelines cannot be produced while the evidence is predicated on the flawed proposition that depression is an “it” (a homogenous construct).4

GPs might well be puzzled by the zeal in academic psychiatry for monotherapy. They are advised to “optimise” monotherapy, but not told what this means. They are very familiar with models of staged polypharmacy for common chronic illnesses such as hypertension, epilepsy, diabetes, and asthma, but in psychiatric pharmacotherapy this is apparently unwise or too risky.

The way such admonishments are usually framed is by reference to serious but rare adverse reactions (like the serotonin syndrome), without proper attention to the equally serious and probably more common problems with the current “simple” psychotropic drug options already used by GPs. Failure to contextualise these risks leads to a distortion of risk–benefit prescribing decisions and an unnecessary restriction of treatment choices.

We must have a commonsense approach to the treatment of depression that recognises the proper context of our knowledge base. Combination antidepressant treatments may be “beyond the evidence”, but this alone is not a sufficient justification to stop using them.

View this article on Wiley Online Library

More like this

Mental health Perspective 20 July 2026 Open Access

Reorienting Allied Health Into Community-Based Care for People Experiencing Trauma and Social Disadvantage

Simon Rosenbaum, Grace McKeon, Gulsah Kurt, Oscar Lederman, Kemi Wright, Sabuj Kanti Mistry, Jackie E. Curtis, Philip B. Ward, Zachary Steel, Hamish Fibbins, Rachel Morell, Melissa C. Eaton, Andrew Watkins, Ben Harris-Roxas, Brendan Goodger, Eleanor Beck, Megan Teychenne, Joseph Firth, Davy Vancampfort, David Burns, Russell Roberts, Tristan Favaloro, Danielle Weber, Rosanna Barbero, Vasili Maroulis, Melissa Holmes, Stefan Mackenzie, Chiara Mastrogiovanni, Afsana Anwar, Uzma Choudhry, Catherine Sherrington, Jane Currie, Thomas Gadsden, Scott Teasdale

View more