The 2016 CANMAT Depression Guidelines: Redefining Levels of Evidence and Levels of Funding

VOL 2 #7

Natasha Snelgrove MD, FRCPC

To much fanfare, and with an entire volume of the Canadian Journal of Psychiatry dedicated to these guidelines, the fourth iteration of the Canadian Network of Mood and Anxiety Treatment (CANMAT) Guidelines for the Management of Adults with Major Depressive Disorder were released in September 2016.

Although the CANMAT guidelines are heralded as Canada’s major treatment guidelines for both depression and bipolar disorder, they are not without controversy, and this newest iteration is not an exception.

Using the same methodology  for defining indicated treatments and levels of evidence as in the past, new treatments were added to the guidelines and some treatments, perhaps surprisingly, were downgraded to second line status.

There have been many criticisms of CANMAT in the past and some of the same arguments still hold.

Firstly, the criteria for levels of evidence are not overly strong – to designate a second line treatment, only one non-placebo controlled RCT of “adequate size” is required. For first line, only two RCTs are required, although it is specified that “placebo controlled is preferred [emphasis added].” (1) There is no indication of what quality standards the RCT must meet, or consideration of the source of funding. There is no systematic way that this can be ascertained and bias eliminated, so the bar for becoming a first line treatment is low.

Secondly it is interesting to note that lithium, in particular, was downgraded, in this newest set of guidelines, to a second line augmentation agent (1). Given the above mentioned inclusion criteria this makes little to no sense.

There is a large amount of evidence supporting not only lithium’s safety and effectiveness in MDD, but also its anti-suicidal properties. CANMAT cites that most studies of lithium augmentation are in combination with tricyclic antidepressants and that studies with serotonin reuptake inhibitors have wide confidence intervals, hence its downgrading. However, these were the same studies that were  available in 2013, when lithium was still indicated as first line. Therefore, it is puzzling that this is the justification for the downgrade.

Following the release of the CANMAT guidelines an article by Stephen Strakowski  in November 2016 still recommends lithium as a first line augmenting agent, and as the best-studied augmenting agent (2). In addition, the NICE guidelines and RANZCP guidelines continue to indicate lithium as first line augmentation, along with specified atypical antipsychotics and other antidepressants (3, 6).

Finally, the majority of the CANMAT authors have financial ties to industry. In fact, of the psychopharmacological paper, 13 of 18 authors have received funding from at least one drug company, and the financial disclosures alone are a half page of the paper (1). Although some may argue that because the ties are equally distributed among all drug companies this does not favour a single drug, I would advance that this means that the CANMAT guidelines are biased towards pharmacological treatment as a whole, particularly newer treatments still on patent. With 15 pages dedicated to psychological treatment and 21 pages dedicated to pharmacological treatments, even the degree of focus seems to give preference to pharmacological treatment.

Furthermore, the CANMAT depression guidelines vary from equivalent guidelines in the UK,  Australia and New Zealand in levels of evidence required to classify treatments as first line. For example, NICE guidelines base their processes on the internationally accepted AGREE II method (4). AGREE II assesses the rigour of guidelines and includes such items as scope and purpose of the guidelines, stakeholder involvement in development and review (including patients and the public), rigour of development including inclusion and exclusion criteria for included studies, clarity, applicability including costs and monitoring of implementation of recommendations, and editorial independence (5).

For the Royal Australian and New Zealand College of Psychiatrists, stakeholder involvement, rigourous external consultation, and review with experts was considered in development (6). Furthermore, in the methods section of the RANZCP guidelines, they note that pharmaceutical company funded trials may induce bias and they note that this was a consideration in the development of their guidelines, to the point that they excluded those authors with specific conflicts of interest in discussion of the relevant sections of the guidelines (6). However, for CANMAT, none of these methods appear to be used as outlined above. This leads to a proliferation of new first-line indicated antidepressants. As such, pharmacology is emphasized, and the guidelines provide minimal real clinical utility in deciding which antidepressants might be preferred – as all are indicated, with all newer antidepressants classified as first line.

The CANMAT depression guidelines are regarded in Canada as our primary depression treatment guidelines and lauded for being such. All final-year Canadian psychiatric residents fervently memorize them for their Royal College exams.

This has the potential to influence both the ability of future psychiatrists to accurately appraise evidence, as well as to influence prescribing practices to our patients. Given this hallowed space within medical education we should demand more from our own guidelines – more scientific rigour, more robust evidence, and less pharmacological industry influence from those designing them. It is time to demand more of our national mood disorder guidelines.

References:

1. Lam et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Update CANMAT Guidelines for Treatment of Major Depressive Disorder. Can Jour Psych; 61:9. September 2016.
2. Strakowski, S. “A Guide To Treating Unipolar and Bipolar Depression.” Epub November 14, 2016 on medscape.com. Accessed November 22, 2016
3. Depression in adults: recognition and management. NICE Clinical Guideline. Published Oct 28, 2009. Accessed April 24, 2017.
4. Developing NICE guidelines: the manual. Published 2014, last updated 2017. Accessed May 3, 2017.
5. Brouwers M, Kho ME, Browman GP, Cluzeau F, Feder G, Fervers B, Hanna S, Makarski J on behalf of the AGREE Next Steps Consortium. AGREE II: Advancing guideline development, reporting and evaluation in healthcare. Can Med Assoc J. Dec 2010.
6. Malhi GS et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Australian and New Zealand Journal of Psychiatry 2015, Vol. 49(12) 1-185.
   

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