From the Editor

“Despite its strong evidence base, clozapine remains grossly under-prescribed in clinical practice. Although reasons for this are multifaceted, a commonly cited influence is the need for mandatory haematological monitoring.” So notes Ebenezer Oloyede (of the University of Oxford) and his co-authors in a new British Journal of Psychiatry paper. Could the requirements be simplified? 

In the first selection, Oloyede et al. look at outcomes of 569 patients on clozapine when, during the pandemic, routine blood monitoring was changed. In this mirror-image cohort study, they find: “[E]xtending the haematological monitoring interval from 4-weekly to 12-weekly did not increase the incidence of life-threatening agranulocytosis in people taking clozapine.” We consider the paper and its implications.

In the second selection, Dr. Rachel H. B. Mitchell (of the University of Toronto) and her co-authors analyze Canadian data on suicide and sex differences. In this Canadian Journal of Psychiatry research article, they find that suicide rates among female adolescents aged 10 to 14 years surpassed similarly aged males in 2011. “The marked and consistent trend of rising suicide rates among adolescent females aged 10 to 14 years in Canada signals increased distress and/or maladaptive coping in this segment of the population.” 

And in the third selection, Alexander Smith (of the University of Bern) and his co-authors write about Vincent van Gogh. In an Editorial for the Australian and New Zealand Journal of Psychiatry, they describe his mental health struggles but also their commercialization. “Vincent van Gogh’s ear has generated an intrinsic cultural currency. Yet, the psychiatric vulnerabilities encompassed by his act of self-harm are not always sensitively considered or acknowledged.”


Selection 1: “Clinical impact of reducing the frequency of clozapine monitoring: controlled mirror-image cohort study”

Ebenezer Oloyede, Olubanke Dzahini, Zadro Abolou, et al.

The British Journal of Psychiatry, 24 April 2023  Online First

Clozapine has been regarded as the gold-standard antipsychotic for treatment-resistant psychosis since the seminal study of Kane and colleagues over three decades ago. Despite its strong evidence base, clozapine remains grossly under-prescribed in clinical practice. Although reasons for this are multifaceted, a commonly cited influence is the need for mandatory haematological monitoring. This monitoring practice is intended to mitigate against the rare but potentially fatal risk of agranulocytosis (reported in 0.4% of patients) associated with clozapine treatment. 

In the UK and many other countries, the frequency of haematological monitoring during clozapine treatment reduces to 4-weekly intervals after 1 year of monitoring at weekly and 2-weekly intervals, and monitoring must be continued until the patient discontinues clozapine. During the COVID-19 pandemic, local guideline changes temporarily permitted patients who were deemed at low risk to have their full blood count (FBC) monitoring extended from 4-weekly to 12-weekly intervals to reduce the risk of exposure to the virus…

Since then, there have been calls for extended monitoring to be implemented in routine practice to help ease restrictions to clozapine use.”

So begins a paper by Oloyede et al.

Here’s what they did:

“All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined.”

Here’s what they found:

  • “A total of 569 patients were included in this study. Of these, 459 were receiving clozapine treatment with extended monitoring at data collection. The total person-years for the intervention group were 458 and the median follow-up time was 1 year.” 
  • Demographics. “The mean age of the intervention cohort was 49 years…, 67% were male and the mean duration of clozapine use was 11 years… The mean age of the comparison group was 48 years…, 66% were male and the mean duration of clozapine use was 14 years…” 
  • NeutropeniaDuring follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48…). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection.” 
  • Admissions. “The median number of admissions per patient during the pre-mirror period remained unchanged during the post-mirror period.”
  • Deaths. “There was one death in the control group, secondary to COVID-19 infection.”

A few thoughts:

1. This is a good study.

2. The main finding in a sentence: “There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.”

3. The clinical implications? “These findings suggest that a significant proportion of patients can safely receive clozapine with extended monitoring.”

4. Like all studies, there are limitations. The authors note several, including that: “patients who received extended monitoring were selected based on an absence of prior haematological events and demonstrated adherence to clozapine. This limits the generalisability of our results because participants were selected who were deemed at low risk of complications with extended monitoring.”

5. This study isn’t spectacular – but it’s very important. Clozapine is under-prescribed. Efforts to simplify the monitoring requirements could help make the medication a more attractive choice for some patients.

The full BJP paper can be found here:

Selection 2: “Sex Differences in Suicide Trends Among Adolescents Aged 10 to 14 Years in Canada”

Rachel H. B. Mitchell, Nicole Kozloff, Marcos Sanches, et al.

The Canadian Journal of Psychiatry, 2 May 2023  Online First

Suicide rates appear to be rising rapidly among youth in North America. Historically, adolescent males have had much higher rates than females; however, this gap may be narrowing due to rising suicides among female adolescents… In Canada, reported rates among females aged 10 to 14 have also steadily increased while rates among males have remained stable or declined.

The ages of 10 to 14 are marked by the onset of puberty, accelerated brain maturation, and, for many, a rapid rise in symptoms of depression and anxiety. These years are also when self-harm commonly emerges and when adolescents are particularly impressionable, with increased susceptibility to social contagion. Prior research has combined the younger ages of 10 to 14 years with older adolescents aged 15 to 19 years; however, this approach risks masking granular data that is essential for detecting emerging trends and informing targeted suicide prevention strategies for this vulnerable group.

So begins a paper by Mitchell et al.

Here’s what they did:

“We used publicly available data from the Canadian Vital Statistics Database to retrieve cause of death information based on the International Statistical Classification of Diseases and Related Health Problems codes on death certificates. Data on suicide were available for all recorded deaths among Canadians aged 10+. We used census data to calculate the annual age- and sex-standardized rate per 100,000 from 2000 to 2018 for youth aged 10 to 14. We used segmented regression analysis to identify up to 3 breakpoints in the suicide rate for each age group and sex based on visual inspection, Bayesian Information Criteria, and by empirically fitting polynomial models to the series. We compared suicide rates between sexes in 2000, 2009, and 2018, fitting a linear model that included sex and an interaction between sex and year. To account for the change in slopes, we added an indicator of the year being larger or equal to the breakpoint in the model, interacting with sex and year. We modelled the outcome on the logarithmic scale to calculate incidence rate ratios at the desired time points…”

Here’s what they found:

“From 2000 to 2009, the suicide rates among adolescents aged 10 to 14 years in Canada decreased in both males and females. In 2009, the suicide rates diverged, remaining stable in males, while increasing at an average rate of 7% per year in females, surpassing males in 2011. The estimated female:male incidence rate ratios in 2000, 2009, and 2018 were 0.85…, 0.76… and 2.08…, respectively. That is, by 2018, the incidence rate ratio had more than doubled, indicating a higher suicide rate among females versus males.”

A few thoughts:

1. This is solid and interesting data, drawing on national databases and covering 18 years.

2. Why the rise in female suicide in this age group? The authors offer several explanations: “the proportion of school-age girls in Canada reporting symptoms consistent with depression – strongly linked to suicide risk – is rising. Mounting societal and gendered pressures in the form of familial stress from the 2008 global financial crisis and its aftermath, or the advent of smartphones and ubiquity of social media may have put disproportionate stress on younger girls. Additionally, changing gender norms and messaging that younger girls are exposed to could influence suicide rates.” 

3. All these explanations seem plausible. We can wonder whether it is the influence of social media on females.

4. Also interesting: females superseding males in this age group is not seen in the United States. The authors suggest that other industrial countries aren’t seeing this trend. 

The full CJP paper can be found here:

Selection 3: “Vincent van Gogh’s ear and the sociocultural iconography of mental illness”

Alexander Smith, Dinesh Bhugra, and Michael Liebrenz

Australian and New Zealand Journal of Psychiatry, June 2023

Vitality leaps from the canvas: twinkling stars, rich sunflowers, phantasmagorical skies and rolling landscapes. Over one hundred and thirty years after his death, the post-impressionist artist, Vincent van Gogh (1853-1890), continually captivates the critical and popular imagination. In the 2020s, Van Gogh exhibitions draw sizable crowds, his work has influenced countless cultural productions, and recently, high-profile climate protests targeted his paintings.

Given this enduring relevance, Van Gogh could be characterised as one of the most prominent European artists. Still, mention him in general conversation and his severed ear will more than likely be referenced. Significantly, this body part has attracted substantial notoriety, engendering an inherent cultural resonance. As we write, Google returns over 5 million results for ‘Van Gogh’s ear’, and an abundance of dedicated merchandise is on sale, from novelty ephemera to earrings and beyond.

So begins a paper by Smith et al.

Van Gogh’s self harm: psychiatric perspectives

“Much conjecture and scholarly attention surround Van Gogh’s act of self-harm, although specific details remain undetermined. Nevertheless, it is generally recognised that in December 1888 in Arles (France), Van Gogh severed his ear with a razor. This followed escalating tensions with Paul Gauguin (1848–1903), a fellow post-impressionist and artistic collaborator staying with Van Gogh in Arles. Afterwards, Van Gogh delivered his ear to a local brothel, before he was admitted to hospital, where the painter could not recall preceding events. This marked the beginning of several periods of in-patient psychiatric care…

“Since his death, psychiatrists have repeatedly hypothesised about Van Gogh’s mental health, based on (then-current) psychiatric knowledge and terminology. With potential indications of heritability, Vincent’s sister, Wilhelmina Van Gogh (1862–1941), may have had schizophrenia and was treated within a psychiatric institution.”

They note the question of epilepsy. “While diagnostic proposals vary, there is general consensus that Van Gogh’s underlying psychopathology led to his act of self-harm. Researchers contend that Van Gogh had various comorbidities, including mood disorder and borderline personality disorder traits, which together with alcohol use and psychosocial stressors resulted in his self-harm.”

Van Gogh’s ear and modern framework of mental illness

“Van Gogh’s ear is frequently accented in commercial settings, where sensitivity towards his mental health is conspicuously absent. Products merchandising Van Gogh’s self-harm, such as figurines with a detachable ear, are sold in gift shops and beyond. Notwithstanding their distasteful portrayals, from an ethical perspective, such items are morally questionable since consent is not available.”

They continue:

“In an era of increasing sincerity towards mental health dialogues, how do we explain commercial appropriation of psychiatric conditions? It is difficult to envision souvenirs that either directly or indirectly reference mental illnesses in recently deceased celebrities not receiving a public backlash. Nonetheless, in Van Gogh’s case, from glib semantics about his psychiatric morbidities to products commemorating his self-harm, the artist’s mental health can often be tactlessly appraised or even disregarded. Does stigma have a time limit?”

The Editorial ends: “We believe that psychiatrists have a duty to challenge these presentations and ensure that, no matter how long ago they lived, an individual’s mental health is appropriately respected in popular and scientific discourse. Presciently, Van Gogh’s own words may serve as a metaphor for enduring tensions between increasing mental health awareness and certain regressive sociocultural presentations: ‘Though I have changed, I am the same’.”

A few thoughts:

1. This Editorial makes good points.

2. A detachable ear? Great art is limited but poor taste knows no bounds.

3. For a more detailed look at Vincent van Gogh’s illness, the late Dr. Dietrich Blumer (of the University of Tennessee) wrote an excellent paper for The American Journal of Psychiatry in 2002. You can find it here:

(And a quick thanks to Dr. Jeff Daskalakis for the suggestion.)

The full ANZJP Editorial can be found here:

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