Antidepressant combination for major depression in incomplete responders-a systematic review.
J Affect Disord. 2012 Jul 24;
Authors: Lopes Rocha F, Fuzikawa C, Riera R, Ramos MG, Hara C
Abstract
BACKGROUND: Antidepressant combination has been suggested as a strategy to increase treatment efficacy. The objective of this study was to perform a systematic review and meta-analysis of studies that assessed the effect of antidepressant combination for major depression in patients with incomplete response to an initial antidepressant.
METHODS: Studies were retrieved from PubMed (1966-February, 2012), Cochrane Library (-February, 2012), Embase (1980-February, 2012), PsycINFO (1980-February, 2012), Lilacs (1982-February, 2012), clinical trials registry, thesis database (www.capes.gov.br), and secondary references. Included studies had an open label phase in which an initial antidepressant was used for the treatment of major depression and a double blind phase for the incomplete responders that compared monotherapy with the first antidepressant versus the association of a second antidepressant to the first one.
RESULTS: Out of the 4,884 studies retrieved, only five satisfied the inclusion criteria. The total number of patients included was 483. Only two small trials reported benefits of adding a second antidepressant to the initial antidepressant. Dropouts due to side effects were not reported in three studies. Meta-analysis was not performed due to the small number of studies, the inconsistency in the direction of effect and the possible instability of effect size. Only limited kinds of combination, involving mianserin, mirtazapine and desipramine were studied. Some properties of the first two drugs such as the anxiolytic, sedative, and orexigenic effects, can mimic depression improvement.
LIMITATIONS: Publication bias cannot be ruled out. Only one study included a monotherapy arm with the antidepressant used for augmentation of the first antidepressant.
CONCLUSIONS: The practice of using a combination of antidepressants for major depression in incomplete responders is not warranted by the literature.
PMID: 22835845
This study goes to show how limited and flawed evidenced-based medicine can be.
Antidepressant Combinations have been used for decades by clinical psychiatrists. Single medications tend to only be partially effective – addressing only a small portion of the pathology in major depressive disorder. Certain combinations of medications – particularly those which address different pathophysiologies of the illness – are more effective for treating depression in clinical experience.
However, finding the evidence for combination treatment is sorely lacking. For one thing, there is no money to do such research – which can run into the millions of dollars. Pharmaceutical companies don’t want to sponsor combination treatment trials since that forces them to pay for studying a competitor’s medication. Thus, other than the clinical experience of psychiatrists through the decades, there is hardly any study nor will there every be.
The conclusion of this study should not have been so harsh given the lack of data (e.g. using “not warranted”) – since concrete thinkers would be lead to believe one should never use combination treatment. This would be a disservice to our patients given the general ineffectiveness of antidepressants. I would rather have it state that there aren’t enough studies on combination treatments and leave it at that – or state that each physician will have to weigh the risks and benefits of using combination treatment in patients (just as is done for any medication during pregnancy where there aren’t enough studies done on safety during pregnancy).
There simply isn’t enough research evidence for many things. Medicine is still part art and craft, not all science. And it is the art of medicine which is often ignored when solely choosing treatment based solely on the research evidence.