Volume 187 - Issue 3
Beyond the evidence: is there a place for antidepressant combinations in the pharmacotherapy of depression?
Authors: Nicholas A Keks, Graham D Burrows, David L Copolov, Richard Newton, Nick Paoletti, Isaac Schweitzer and John W G Tiller
Med J Aust 2007; 187 (3): 198-200. || doi: 10.5694/j.1326-5377.2007.tb01194.x
Published online: 6 August 2007
Published online: 6 August 2007
In reply: The letters by Horgan and Walters et al underline our motive for reviewing antidepressant combinations. The conclusions of the survey are at least questionable, given that the response rate was only 36%, 18% of respondents were not psychiatrists, and affirmative responders may have only used combination antidepressants once.1 In any case, should clinical popularity substitute for evidence? If so, once popular but now research-discredited treatments such as insulin coma therapy would still be used.
Equating combination antidepressants to combination drugs for asthma and hypertension is misleading. How often are two β-blockers given together in maintenance treatment? Major depression causes severe suffering, but this does not justify the use of unproven treatments ahead of those supported by evidence.
General practitioners should be informed about antidepressant combinations, but the information must be evidence-based. We described the process of dose optimisation, and stand by our advice that complex cases that require unproven treatment (such as combination antidepressants) be referred to a psychiatrist.
Patients should also be informed about combination antidepressants, including the paucity of evidence concerning efficacy and safety, the absence of information about consequences of long-term treatment, and that some combinations are lethal and others frequently unsafe.
Published data from the STAR*D study provide equivocal support for the combination of citalopram and bupropion, as we noted. Evidence of modest effectiveness (remission rate, 13.7%) for the combination of mirtazapine and venlafaxine has appeared.2
Our conclusion was that some antidepressant combinations could be used in certain clinical situations where evidence-based treatments have failed, with safeguards. Given that 17% of respondents to the survey1 observed serious complications with combination antidepressants, this is good advice.
References
- Horgan D, Dodd S, Berk M. A survey of combination antidepressant use in Australia. Australas Psychiatry 2007; 15: 26-29.<eMJA full text>
- McGrath PJ, Stewart JW, Fava M, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry 2006; 163: 1531-1541. 0_CBBHCAFC