Some of the CANMAT Recommendations for the Pharmacological Treatment of Late-life Depression Are Not Congruent with Available Evidence or Expert Opinion

Abstract

Dear Editor:

The Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines have become important references for clinicians and learners in Canada and elsewhere. Thus, we welcome the publication in the Canadian Journal of Psychiatry of new guidelines focusing on special populations, including a well-written section on the treatment of late-life depression.¹ However, we are concerned by the typographical errors and possible mistakes in Table 6, some of which could potentially lead to patient harm:

Duloxetine is listed twice among recommended first-line treatments, those with level 1 and those with level 2 evidence.

Combining a selective serotonin reuptake inhibitor (SSRI) with another SSRI or with a serotonin-norepinephrine reuptake inhibitor (SNRI) is recommended as a third-line treatment with Level 3 evidence. Not only is there no evidence supporting this combination in older adults, but it could cause a serotonergic syndrome and death.²

Amitriptyline and imipramine are also recommended as third-line treatment options. These tertiary amine tricyclic antidepressants are associated with high rates of postural hypotension and anticholinergic effects.³ Nortriptyline has the same mechanism of action, and it is better tolerated by older patients.³ Thus, both amitriptyline and imipramine are on the Beers List of medications that should be avoided in older adults.⁴ Neither of these medications is recommended by older geriatric guidelines^5,6 or by more recent adult guidelines.^7,8

Finally, bupropion, citalopram, escitalopram, desvenlafaxine, mirtazapine, moclobemide, and venlafaxine are recommended as treatments with Level 1 or 2 evidence. While we agree with the recommendation of considering these antidepressants for depressed older adults, there is no Level 1 or 2 evidence (as defined by CANMAT⁹) supporting their use in older adults. There are no published randomized controlled trials (RCTs) of desvenlafaxine, and the placebo-controlled RCTs of bupropion, citalopram, escitalopram, mirtazapine, moclobemide, and venlafaxine are negative.¹⁰

It appears that only one of the authors of Table 6 is a geriatric psychiatrist. Thus, it is unclear who the experts were who assigned the levels of evidence or lines of treatment.⁹ It is also unclear whether Table 6 was peer-reviewed by geriatric psychiatrists or other stakeholders involved in the clinical care of depressed older adults.

Because the CANMAT guidelines are widely used, we respectfully suggest that CANMAT and the Canadian Journal of Psychiatry retract Table 6 and provide a corrected version, hopefully based on the consensus of a broad community of experts.

Daniel Blumberger, MD, MSc, FRCPC David Conn, MB, FRCPC John S. Kennedy, MD, FRCPC Benoit H. Mulsant, MD, MS, FRCPC Bruce G. Pollock, MD, PhD, FRCPC, FCP Kiran Rabheru, MD, CCFP, FRCPC Mark J. Rapoport, MD, FRCPC Dallas Seitz, MD, PhD, FRCPC

Footnotes

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Benoit H. Mulsant reports non-financial support outside the submitted work from Bristol Myers Squibb, Eli Lilly, and Pfizer. Dr. Mulsant is the Chair of the Department of Psychiatry, University of Toronto, and a Board Member, Centre for Addiction and Mental Health, Toronto. Both institutions have multiple financial relationships with pharmaceutical and biomedical companies. John S. Kennedy is a former employee and current stockholder of Eli Lilly.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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