From the Editor

It’s Canada Day.

Let’s start by noting that not everyone has a day off. Some of our colleagues are working – perhaps in hospitals or vaccine clinics. A quick word of thanks to them for helping our patients on a holiday.


Appropriately, this week’s selections will focus on Canadian work.

What makes a paper “Canadian” for the purposes of this review? That is, how do we define Canadian? Things could get complicated quickly when considering journal papers. Does the second author order “double double” at Tim Hortons? Has the senior author eaten poutine for breakfast? Is the journal’s action editor hoping that the Canadiens bring the Cup home?

Let’s keep things simple: all the papers selected this week have been published in a Canadian journal and the papers are clinically relevant for those of us seeing patients in Canada.

There are many papers that could have been chosen, of course. I’ve picked five papers – a mix of papers that have been featured previously in past Readings, and some new ones. All but one of the selected papers are recent.

Please note that there will be no Readings for the next two weeks.



“A Systematic Review of Nutraceuticals for the Treatment of Bipolar Disorder”

Melanie M. Ashton, Bianca E. Kavanagh, Wolfgang Marx, et al.

The Canadian Journal of Psychiatry, March 2021

One treatment avenue currently being explored is the adjunctive use of nutrient-based compounds. Nutraceuticals have been defined as standardized nutrients, or functional foods, with a pharmaceutical manufacturing grade, and can be used to potentially treat or prevent a disorder or disease. These compounds can be viewed as the intersection between pharmaceuticals and nutrition.Nutraceuticals can target biological processes including neurogenesis, inflammation, oxidative stress, and mitochondrial function, which are all known to be dysregulated in BD. For example, omega-3 fatty acids are known for their anti-inflammatory properties, vitamin D as an antioxidant and compounds such as coenzyme Q10 are involved in mitochondrial biogenesis. There are also amino acids such as N-acetylcysteine (NAC) which can show effects on these processes in BD. Nutraceuticals are readily available, affordable, and acceptable by the public, and therefore, they may be potential adjunctive treatments for BD.

Ashton et al. write this in their systematic review.

The methods

“A total of 1,712 studies were identified through the search. After rigorous screening, 22 studies were included in the review. There was large variability across the studies with 15 different nutraceutical agents assessed and as such insufficient homogeneity for a meta-analysis to be conducted ”

The important findings

“Regarding bipolar depression, a study of coenzyme Q10 was positive, albeit from only a single study. Studies of omega-3 fatty acids and NAC reported both positive and negative results for treating bipolar depression. For α-lipoic acid, citicoline, creatine, inositol, SAMe, folic acid, and vitamin D, only single negative studies have been reported.

“In regard to the treatment of mania, positive results have been reported for 1 folic acid and 1 small NAC study. Treatment with tyrosine-depleting amino acids found positive results in 2 studies. Studies of tryptophan depletion were conflicting with both positive and negative results. Finally, 1 study of omega-3 fatty acids for the treatment of mania returned negative results.”

The take-away

While it’s difficult to criticize a patient’s decision to take supplements like omega-3 fatty acid for bipolar, there isn’t much evidence currently of its benefits, either for those with bipolar depression or mania.

The link


“Are There Therapeutic Benefits of Cannabinoid Products in Adult Mental Illness?”

Philip G. Tibbo, Kyle A. McKee, Jeffrey H. Meyer, et al.

The Canadian Journal of Psychiatry, February 2021

In response to the federal government legalizing and regulating access to cannabis in 2017, the CPA published a position statement with respect to cannabis use and adverse health consequences in youth and young adults based on the accumulating evidence of negative consequences of early sustained use (e.g., National Academies of Sciences and Medicine, 2017). However, psychiatrists and other mental health professionals are also being asked about the potential therapeutic uses of cannabis and cannabinoid products for mental illnesses; information is widely distributed on cannabis use being associated with mental wellness and suggesting cannabis use as a treatment for a variety of mental health concerns. As the CPA is evidence based, it is prudent to examine the existing research in this area to inform our membership needs and thus the public.

Tibbo et al. make this comment early in their CPA position statement.

The methods

“The CPA has systematically reviewed the existing literature on RCTs examining potential beneficial uses of cannabis and cannabinoid products to treat mental illness. This review incorporated studies in adults only (greater than 18 years old). Of the 1,982 papers identified, 29 RCTs were available to review… Methodological quality for each study was assessed using Cochrane Collaboration guidelines.”

The important findings

The CPA –

  • “Acknowledges there is some limited evidence for use of cannabinoid products (excluding combustible dried cannabis and cannabis edibles) for the treatment of mental illness, but the evidence base is currently of low-quality and below that required to meet Level 1 evidence.”
  • “Strongly discourages cannabis and cannabinoid product use by anyone experiencing mental illness. Use of cannabis or a cannabinoid product should never delay (or replace) more evidence-based forms of treatment. We encourage patients to discuss potential harms of use with their treating physician.”

The position paper “recommends that any discussion of the potential therapeutic benefit of cannabinoid products be balanced with the risk for adverse outcomes (e.g., worsening of the underlying illness, addiction, cognitive impairment) and should be within the context of the methodology of the current RCTs, which includes carefully chosen cannabinoid products, dosing, side effect monitoring and regimented drug administration.”

The take-away

Our patients are asking more and more about cannabis, but the evidence of its efficacy is thin. Of course, this paper was published almost a year ago, but it remains highly relevant – new papers, including in The Canadian Journal of Psychiatry, haven’t found any newer evidence.

The link


Pregnancy and Delivery Outcomes Following Benzodiazepine Exposure: A Systematic Review and Meta-analysis

Sophie Grigoriadis, Lisa Graves, Miki Peer, et al.

The Canadian Journal of Psychiatry, December 2020

While benzodiazepines (BZDs) are frequently prescribed for anxiety disorders, there are recommendations to limit their use. These drugs are generally not first-line treatment, but prescribing patterns suggest that they are used long term. Exposure during pregnancy can occur continuously or ad hoc, and research suggests the use of antianxiety medications during pregnancy has been increasing over time. A large Swedish study (1996 to 2011) reported that sedatives/hypnotics were the third most commonly used central nervous system active drug in pregnancy, following antidepressants and opioids; 4.6% of infants were exposed to sedatives/hypnotics during the first trimester. As such, knowledge about their safety during pregnancy is important, yet our understanding of their effects on maternal and fetal health remains incomplete.

So begins a systematic review and meta-analysis by Grigoriadis et al.

The methods

“English-language cohort studies comparing antenatal BZD exposure to an unexposed group on any delivery outcome were eligible. In all, 23,909 records were screened, 56 studies were assessed, and 14 studies were included.”

The important findings

“Adverse effects following maternal use of BZDs during pregnancy were significantly associated with 6 outcomes overall, but 8 with an adjusted effect accounting for publication bias. There was significant heterogeneity for most outcomes, which suggests that confounding cannot be ruled out, although a consistent factor did not seem to emerge in the moderator analyses. Regardless, the magnitude of the majority of the pooled ORs approximated 2, which many experts believe is the threshold for clinical significance.”

The take-away

Though this class of medications has fallen out of fashion, benzodiazepines remain prescribed – including to women of child-bearing age. This paper reminds us that caution is required.

The link


“Major Depression in Canada: What Has Changed over the Past 10 Years?”

Scott B. Patten, Jeanne V. A. Williams, Dina H. Lavorato, et al.

The Canadian Journal of Psychiatry, February 2016

Major depression has been identified as a global public health priority and was ranked by the Global Burden of Disease Project as the second leading cause of disability adjusted life years in Canada. While efforts have been made to compare different countries in terms of the prevalence and correlates of major depressive episode (MDE), it has not generally been possible to make comparisons over time within countries due to modifications made to diagnostic interviews. Comparisons over time are important for discerning whether progress against this condition is being made. Improved access to treatment and more effective treatment can theoretically decrease the prevalence and impact of this condition. It is important to know whether such progress is occurring.

So begins a paper by Patten et al.

The methods

“The epidemiology of MDE in the national population has been examined in 2 mental health surveys, one conducted in 2002 and the other in 2012. Our objective was to compare selected variables from the 2 surveys to determine whether changes have occurred in the prevalence, treatment, and impact of MDE.”

The important findings

The authors considered “potentially adequate treatment” – that is, whether people received therapy (six or more visits to social workers and psychologists) or antidepressants.

There is good news and bad news: “Combined with [antidepressant] use as an indicator of potentially adequate treatment, 52.2%… of people with past-year MDE were receiving potentially adequate treatment, compared with 41.3%… in 2002.”

The take-away

While there has been progress (potentially adequate treatment has risen from 41.3% to 52.2%), many Canadians are under-treated for depression. So, clinically, a good history is needed of past treatments. This paper – which isn’t particularly new but remains very relevant – suggests that ongoing work is needed to provide evidence-based care to our patients.

The link


“Changes to the Psychiatric Chatbot Landscape: A Systematic Review of Conversational Agents in Serious Mental Illness”

Aditya Nrusimha Vaidyam, Danny Linggonegoro, John Torous

The Canadian Journal of Psychiatry, April 2021

The need for digital tools in mental health is clear, with insufficient access to mental health services worldwide and clinical staff increasingly unable to meet rising demand…

Conversational agents, also known as chatbots or voice assistants, are digital tools capable of holding natural language conversations and mimicking human-like behavior in task-oriented dialogue with people. Conversational agents exist in the form of hardware devices such as Amazon Echo or Google Home as well as software apps such as Amazon Alexa, Apple Siri, and Google Assistant. It is estimated that 42% of U.S. adults use digital voice assistants on their smartphone devices, and some industry studies claim that nearly 24% of U.S. adults own at least 1 smart speaker device. With such widespread access to conversational agents, it is understandable that many are interested in their potential and role in health care…

The methods

“A systematic literature search was conducted in January 2020 using the PubMed, Embase, PsychINFO, and Cochrane databases. Studies included were those that involved a conversational agent assessing serious mental illness: major depressive disorder, schizophrenia spectrum disorders, bipolar disorder, or anxiety disorder.”

The important findings

“Conversational agents have continued to gain interest across the public health and global health research communities. This review revealed few, but generally positive, outcomes regarding conversational agents’ diagnostic quality, therapeutic efficacy, or acceptability. Despite the increase in research activity, there remains a lack of standard measures for evaluating conversational agents in regard to these qualities.”

The take-away

Your patients ask about chatbots and The New York Times reports on them but – so far – there is little evidence whether these programs help.

The link


Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.