From the Editor

Last week, I met a person who had deeply unsettling auditory hallucinations. I asked him the questions that we all ask: When did the voices start? How many voices do you hear? Do the voices tell you to do things? In contrast, while we know that people with psychotic illnesses can have visual hallucinations, we rarely inquire about them and if we do, it’s in a perfunctory manner, as I did with him. Clinicians aren’t the only ones to gloss over visual hallucinations; they tend to be under-researched, especially with regard to long-term outcomes.

In the first selection, Isabel Kreis (of the University of Oslo) and her co-authors look at outcomes and visual hallucinations in an impressive, new study published in Schizophrenia. They report on 184 people from Norway with first-episode psychosis, followed for ten years, with a focus on visual hallucinations and functionality, suicide attempts, and childhood trauma. “These findings highlight the relevance of assessing visual hallucinations and monitoring their development over time.” We consider the paper and its implications.

In the second selection from CMAJ, Shaleesa Ledlie (of the University of Toronto) and her co-authors report on opioid-related deaths in Canada. They drew from a national database and looked at several years of data, including over the start of the pandemic. “Across Canada, the burden of premature opioid-related deaths doubled between 2019 and 2021, representing more than one-quarter of deaths among younger adults.”

And in the third selection, Dr. Roy Perlis (of Harvard University) argues that the time has come for over-the-counter antidepressants in a STAT essay. He notes that many people with depression are untreated and that increasing the availability of these medications would be helpful. “With part of the solution hiding in plain sight, it’s time to do everything possible to give Americans another way to get treatment.”

DG

Selection 1: “The relationship between visual hallucinations, functioning, and suicidality over the course of illness: a 10-year follow-up study in first-episode psychosis”

Isabel Kreis, Kristin Fjelnseth Wold, Gina Åsbø, et al.

Schizophrenia, 2 March 2024

In contrast to the vast research on auditory hallucinations in psychotic disorders, comparatively little attention has been devoted to visual hallucinations. This may be because auditory hallucinations appear to be more common in psychotic disorders, whereas visual hallucinations have traditionally been linked to organic and neurodegenerative conditions. However, recent meta-analyses indicate that visual hallucinations are less rare in psychosis than previously assumed, with a weighted mean prevalence of 33% in first-episode psychosis (FEP) and 27% in schizophrenia…

Visual hallucinations tend to co-occur with hallucinations in other, especially auditory modalities, and are often experienced as simultaneous-multimodal hallucinations (e.g., talking images). Notably, they are associated with a range of illness severity markers, including higher global, as well as domain-specific symptom severity, a larger number of psychiatric comorbidities, longer time spent in acute psychosis, higher administered doses of antipsychotic medication, and a lower age at onset…

These findings suggest that visual hallucinations may be a risk indicator for a more severe illness course, culminating in larger functional impairments and increased suicidal behavior.

So begins a paper by Kreis et al.

Here’s what they did:

  • They conducted a “prospective longitudinal study involving individuals with first-episode psychosis.”
  • They were recruited from the Norwegian regions of Oslo, Østfold, and Innlandet from 2004 to 2012. 
  • “All patients met the diagnostic criteria for an affective or a non-affective psychotic disorder and had experienced, or were currently experiencing, at least one psychotic episode.” 
  • Participants were assessed with semi-structured clinical interviews, as well as self-report questionnaires at baseline and 10-year follow-up, including the Childhood Trauma Questionnaire (CTQ). 
  • “Participants were grouped based on lifetime experience of visual hallucinations: before or at baseline (VH+/+), first during follow-up (VH−/+), or never (VH−/−).” 
  • “Associations with functioning, suicide attempts, childhood trauma and other markers of illness severity were tested using multinomial logistic regression analysis.”

Here’s what they found:

  • 454 participants had information on visual hallucinations. Many were lost to follow-up, including 150 who withdrew, or had incomplete interviews, leaving a sample of 184.
  • Diagnosis. Many had a primary diagnosis of schizophrenia (n = 84). 
  • Visual hallucinations. At the 10-year follow-up, 50% never experienced visual hallucinations (VH−/−). The majority with visual hallucinations (37.5%) had had such experiences at baseline (VH+/+), and a smaller group (12.5%) at follow-up only (VH−/+).
  • At baseline. The VH+/+ group (37.5%), but not VH−/+ (12.5%), had poorer functioning, higher symptom severity, a lower age at onset, and included more individuals with a history of multiple suicide attempts than the VH−/− group (50%). 
  • At follow-up. The VH−/+ group, but not VH+/+, had poorer functioning and higher symptom severity than the VH−/− group.
  • Suicide. “Visual hallucinations that arise early in the course of illness are a risk indicator for repeated suicide attempts throughout the illness course.”
  • Childhood trauma. There was no association with visual hallucinations.

Some thoughts:

1. This is an interesting study with good data, published in a major journal.

2. The main finding in a sentence: the onset of visual hallucinations was tied to poorer functioning and greater symptom severity.

3. As has been found in other studies, visual hallucinations aren’t so rare. We just don’t ask about them. But should we? The authors argue yes: “They highlight the importance of routinely assessing the presence of visual hallucinations in clinical settings as a risk indicator for repeated suicide attempts and functional impairments.”

4. There is something fresh about this paper given the general lack of interest in visual hallucinations.

5. Of course, there are limitations, as with all studies. The authors note several, including the over-representation of people with bipolar disorder who had suicide attempts at baseline, and the reliance on the GAF scale to measure functionality.

6. This week’s Reading opens with a drawing of a visual hallucination by artist Kate Fenner, who has schizophrenia. Her art depicts her experiences with that illness and has been featured on different websites, including this one:

https://www.boredpanda.com/18-year-old-schizophrenic-artist-drawing-hallucinations/

The full Schizophrenia paper can be found here:

https://www.nature.com/articles/s41537-024-00450-8

Selection 2: “Opioid-related deaths between 2019 and 2021 across 9 Canadian provinces and territories”

Shaleesa Ledlie, David N. Juurlink, Mina Tadrous, et al.

CMAJ, 15 April 2024 

In Canada, the COVID-19 pandemic occurred in the midst of a growing drug toxicity crisis. Before the emergence of COVID-19, the number of accidental opioid-related deaths across Canada rose from 2470 in 2016 to 3447 in 2019. This was accompanied by rising opioid-related hospital admissions and growing infectious complications associated with substance use. Although both prescription and unregulated opioids contribute to toxicity deaths, the relative contribution of these substances has changed considerably over time, with fentanyl from the unregulated drug supply involved in more than 80% of opioid-related deaths in recent years (2020 to early 2023). 

The observed acceleration in opioid-related harm across Canada has been attributed in part to public health measures implemented to curb the spread of SARS-CoV-2, including reduced access to harm reduction programs and border restrictions that may have increased the toxicity of the drug supply. In addition, for many, the pandemic exacerbated feelings of anxiety, uncertainty, and loneliness, contributing to increased substance use globally.

So begins a paper by Ledlie et al.

Here’s what they did:

  • They conducted “a repeated cross-sectional analysis of all opioid-related deaths in 9 Canadian provinces and territories, with data collected at annual intervals between Jan. 1, 2019, and Dec. 31, 2021.”
  • They drew the data from Public Health Agency of Canada, covering 98.0% of the population.
  • The primary measure: the burden of premature opioid-related death, measured by potential years of life lost.

Here’s what they found:

  • Total deaths. “Between 2019 and 2021, the number of accidental opioid-related deaths increased 107%, from 3 007 to 6 222 deaths per year, across the 9 Canadian provinces and territories.” 
  • YLL. The annual years of lost life (or YLL) doubled over the study period, from 126 115 in 2019 to 256 336 in 2021. 
  • Demographics. “In 2021, the highest burden of deaths was observed among males (181 525 YLL) and young adults aged 20–29 years (64 127 YLL) and 30–39 years (87 045 YLL). Each year, more than 70% of all opioid-related deaths occurred among males (73.9% in 2021) and around 25% of deaths occurred among people between the ages of 30 and 39 years (29.5% in 2021).” 
  • Age. The average percentage of all deaths increased across all age groups. In 2019, 1.7% of deaths among people younger than 85 years were related to opioids, increasing to 3.2% in 2021.
  • Time-series analysis. “Between the first quarter of 2016 and the last quarter of 2022, the quarterly rate of opioid-related deaths increased 187.5%, from 1.6 to 4.6 per 100 000 population.” 

A few thoughts:

1. This is an important study with good data.

2. A summary of the big finding: a sharp increase in opioid-related deaths across all age groups. 

3. Devastating.

4. The study period included the start of the pandemic. The authors note: “After the declaration of a pandemic-related state of emergency in the first quarter of 2020, we observed a significant ramp increase of 0.27… per 100 000 population quarterly in the overall rate of opioid-related deaths.”

5. Like all good studies, they raise more questions than they answer. As we move past the pandemic, will substance-related deaths drop back down? Is this the new normal?

6. The authors note limitations, including the lack of adequate data in four provinces and territories and some pending data with ongoing coroner’s investigations.

The full CMAJ paper can be found here:

https://www.cmaj.ca/content/196/14/E469

Selection 3: “The time has come for over-the-counter antidepressants”

Roy Perlis

STAT, 8 April 2024 

These medications, which have been used in the U.S. for three decades, have repeatedly been shown to be safe and effective for treating major depression and anxiety disorders.

The need for accessible depression treatment has never been greater. Multiple national surveys, including one I help lead, report high levels of depression.

Anyone can now walk into a pharmacy in the United States and buy oral contraceptives over the counter without a prescription, thanks to the FDA’s approval of norgestrel (Opill). This change reflects the drug’s safety and the public health imperative to ensure wider access to birth control. But another safe class of medicine that addresses a massive public health need remains unavailable except by prescription: the antidepressants known as selective serotonin reuptake inhibitors (SSRIs).

So begins an essay by Dr. Perlis.

He notes problems with mental health care:

  • Access. “Access to psychiatrists is extremely limited in many areas of the U.S.: long wait times make a mockery of the 2008 mental health parity mandate. That means the vast majority of antidepressants are prescribed by non-psychiatrists, particularly primary care physicians. Yet many primary care practices struggle to provide the same kind of care for depression that they provide for other chronic illnesses.”
  • The illness. “People with depression may be uncomfortable talking about their symptoms, or simply unable to schedule and keep appointments because of work or family obligations. Depression itself can make it harder to plan and follow through.”

What’s to be done? He advocates that antidepressants be available over the counter. He notes that the FDA allows for non-prescription medications meeting three criteria: “they can be used for self-diagnosed conditions; there’s no need for a clinician’s involvement to be used safely; and they have a low potential for misuse and abuse.” 

Self-diagnosis? “In reality, many OTC products treat symptoms or rely on consumers to diagnose themselves — think yeast infections, acid reflux, or respiratory infections. In the case of major depression or generalized anxiety, screening surveys have been developed for primary care that could help people determine their likely diagnosis with at least the degree of confidence of many OTC applications.”

Safety? “Depression is associated with increased risk for suicide, and medication overdose is among the most common methods of suicide. But walk through the aisles at your local pharmacy and pick any given medicine off the shelf: the odds are good it is more dangerous in overdose than an SSRI.”

He does acknowledge that there are alternatives. “Certain talk therapies, like cognitive behavioral therapy, can be as effective as antidepressants, and some people prefer talking with a therapist to taking a medicine. But not everyone: weekly visits for eight to 12 sessions or more can entail substantial time and money. Here too, access to psychotherapists is a massive problem…”

“Allowing over-the-counter access is not a panacea, but could open the door to a safe, effective, and inexpensive treatment for many who need it.”

He outlines the next steps. “What’s needed to make this happen? An SSRI manufacturer with the courage to engage with the FDA and invest the necessary resources for a prescription-to-OTC switch, a well-trod path that has previously included medicines for allergies, acid reflux, and emergency contraception, among others. This process would primarily involve studies to prove that consumers can understand and follow the medication label, not new clinical trials…”

A few thoughts:

1. This is a good and well-argued essay.

2. How exactly may the proposal work? On X (formerly Twitter), Dr. Perlis suggests that sertraline would be available but only at a lower dose. Does such restricted measure address safety concerns? 

3. Would such strict limits somewhat undermine the effort?

4. Regardless of your view of his proposal, Dr. Perlis is right about the challenges accessing mental health services in the United States (and, for that matter, everywhere else). Is a better solution training up primary care to be more comfortable managing mental disorders?

5. Do you passionately favour Dr. Perlis’ idea? Are you cool to it? As always, the Reading of the Week invites letters to the editor.

The full STAT essay can be found here:

https://www.statnews.com/2024/04/08/time-is-right-for-over-the-counter-antidepressants/

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