From the Editor

It’s the 10th anniversary of the Reading of the Week. The program has grown and evolved over this past decade, now reaching psychiatrists and residents internationally, but the core idea – timely summaries of the latest in the literature coupled with commentary – hasn’t changed. To mark the anniversary, we look at some important papers that we have covered in the past ten years.

Last week: ten papers that I think about often (and helped change my clinical work).

This week: ten papers that I think about often (and helped change the way I view mental illness).

*      *      *

In the second selection, Jesus Montero-Marin (of the University of Oxford) and his co-authors consider mindfulness-based cognitive therapy in a new Viewpoint for JAMA Psychiatry. Noting the burden of depression, they see this therapy as being helpful, especially for those with “entrenched” depression. “By leveraging translational science, we can enhance access, engagement, and treatment outcomes for depression. This work uses MBCT as a foundational case study and delineates future research directions with the potential to profoundly impact service design and policy.”

And in the third selection, journalist Elie Dolgin reports on the new FDA-approved schizophrenia medication for Nature. He describes the novel mechanism of action and quotes Christoph Correll (of Hofstra University): “This will be a revolution of the treatment of psychosis, and I’m not saying this lightly. Now we will now be able to treat people who haven’t been helped with traditional antipsychotics.”

DG

Selection 1: “Ten Papers That I Think About Often (and Helped Change the Way I View Mental Illness)”

October 2024

1. “Breaking the Stigma — A Physician’s Perspective on Self-Care and Recovery”

Adam B. Hill

The New England Journal of Medicine, 23 March 2017

“My name is Adam. I am a human being, a husband, a father, a pediatric palliative care physician, and an associate residency director. I have a history of depression and suicidal ideation and am a recovering alcoholic.”

This paper – published in The New England Journal of Medicine, no less – describes a physician’s journey, from illness to recovery to advocacy. Mental illness can happen to anyone; Dr. Hill reminds us that our white coats aren’t made of Kevlar (to borrow a line from Dr. David Goldbloom).

https://davidgratzer.com/reading-of-the-week/reading-of-the-week-breaking-the-stigma-dr-adam-b-hill-on-his-depression-and-addiction/

2. “My Lovely Wife in the Psych Ward”

Mark Lucach

Pacific Standard, 12 January 2015

“There’s no handbook on how to survive your young wife’s psychiatric crisis. The person you love is no longer there, replaced by a stranger who’s shocking and exotic. Every day I tasted the bittersweet saliva that signals you’re about to puke. To keep myself sane I hurled myself at being an excellent psychotic-person’s spouse.”

This essay is a must read. Indeed, it’s nearly perfectly written. This essay details the life and illness of Lucach’s wife. He talks about her ups and downs, her victories and setbacks, her admissions and discharges. Primarily, though, it’s a love story.

We encounter many families when we work with those who have mental illness. This essay reminds us clearly and lucidly that mental illness touches patients, yes, but also families.

https://davidgratzer.com/reading-of-the-week/reading-of-the-week-my-lovely-wife-in-the-psych-ward/

3. “Identifying outcomes for depression that matter to patients, informal caregivers, and health-care professionals: qualitative content analysis of a large international online survey”

Astrid Chevance, Philippe Ravaud, Anneka Tomlinson, et al.

The Lancet Psychiatry, August 2020

This isn’t a great paper – the language is clunky – but is an important one. Drawing on survey data, the authors note the differences across different domains among the agendas of patients, caregivers, and providers.

For example, consider suicidal ideation: “Participants considered several relevant dimensions, such as the intensity of suicidal ideation, the effort made to fight these ideas, and the emotional consequences (fear, guilt, shame, and psychological distress). These components do not align with how suicidal ideation is measured in common depression scales (or in the DSM-5 diagnosis of major depressive disorder), which highlights the importance of qualitative work involving stakeholders.”

The findings aren’t surprising – but they remind us that patients and their families don’t quite have the same agenda as we do.

https://davidgratzer.com/reading-of-the-week/reading-of-the-week-depression-outcomes-what-matters-to-patients-lancet-psych-also-nyt-on-mental-health-apps-and-startup-culture/

4. “The Name of the Dog”

Taimur Safder

The New England Journal of Medicine, 4 October 2018

“It was July 1, my first day of residency, and a queasy feeling lodged in my stomach as I donned my new white coat. It was different from the previous ones I’d worn – not just longer, but heavier. I was carrying in my pockets everything I thought I needed as a freshly minted doctor: my three favorite pens, a glossy Littmann Cardiology III stethoscope, copies of studies related to my patient with cirrhosis… During morning rounds, I had presented a patient who was admitted for chest pain after walking his dog. My attending had asked, ‘What was the name of his dog?’”

This paper isn’t about mental health. It’s about all of health care.

Remember: life is about the details.

https://davidgratzer.com/reading-of-the-week/reading-of-the-week-the-name-of-the-dog-dr-tafders-excellent-nejm-paper-more/

5. “To Hell and Back: Alcoholism, addiction and lessons they taught me”

Jim Coyle

The Star, 14 May 2014

“It was not for lack of evidence that I would not admit to being an alcoholic – not, at least, until I’d broken the hearts of almost everyone who cared about me and was close to losing everything in my life that mattered.”

As clinicians, we often hear about the impact of substance on our patients lives. This essay – more than 12 000 words long – details Coyle’s struggles with alcohol in an honest and unvarnished way. 

My take-away: the people who battle substance problems are often the strongest and bravest people you will ever meet.

https://davidgratzer.com/reading-of-the-week/reading-of-the-week-the-best-of-2014/

6. “‘I Can’t Crack the Code’: What Suicide Notes Teach Us about Experiences with Mental Illness and Mental Health Care”

Zainab Furqan, Mark Sinyor, Ayal Schaffer, et al.

The Canadian Journal of Psychiatry, February 2019 

The task was grim: working with the Office of the Chief Coroner for Ontario, Furqan and her co-authors looked through dozens of suicide notes, using a constructivist grounded theory approach, and finding different themes.

Twelve people, for instance, “described a strong sense of fatigue associated with their path to suicide.” The composite quotation that they generated: “I am exhausted from trying to fix everything. No one understands, not even doctors or my family, and I keep trying to get help. I feel like I’m a dead man walking for a long time. I’ve been judged by society and have been made to feel ashamed. I’m burned out and tired and trying to find some way to rest.”

This paper helps cast suicide in a different light. And, yes, I ask every suicidal patient about exhaustion.

https://davidgratzer.com/reading-of-the-week/reading-of-the-week-suicide-notes-also-mukherjee-on-case-reports/

7. “I Achieved My Wildest Dreams. Then Depression Hit.”

Alexi Pappas

The New York Times, 7 December 2020

Pappas has had a remarkable life. She competed at the Olympics and graced the cover of Sports Illustrated. She’s also struggled with depression.

In this video essay, she talks about her illness and recovery. She focuses on athletes – but her message is universal. She is particularly moving when discussing her mother’s suicide: “I’ve had such misunderstanding for my own mom, and such resentment towards her. I thought she just didn’t love me enough to stay. That’s not true. She was sick… She didn’t have to die. And that’s so sad because we would have been really good friends, I think.”

https://davidgratzer.com/reading-of-the-week/reading-of-the-week-more-covid-more-mental-health-problems-also-e-cigarette-use-cjp-and-pappas-on-her-olympics-her-depression-nyt/

8. “The lived experience of psychosis: a bottom-up review co-written by experts by experience and academics”

Paolo Fusar-Poli, Andrés Estradé, Giovanni Stanghellini, et al.

World Psychiatry, June 2022

“Something as basic as grocery shopping was both frightening and overwhelming for me. I remember my mom taking me along to do grocery shopping as a form of rehabilitation… Everything seemed so difficult.” So comments a patient on the experience of a relapse of psychosis.

We usually describe psychosis with lists of symptoms. But how do patients understand these experiences? In this World Psychiatry paper, Dr. Paolo Fusar-Poli (of King’s College) and his co-authors attempt to answer this question with a “bottom-up” approach. As they explain: “To our best knowledge, there are no recent studies that have successfully adopted a bottom-up approach (i.e., from lived experience to theory), whereby individuals with the lived experience of psychosis (i.e., experts by experience) primarily select the subjective themes and then discuss them with academics to advance broader knowledge.”

The paper is refreshing – and a nice presentation of patients’ experiences.

https://davidgratzer.com/reading-of-the-week/reading-of-the-week-lived-experience-also-the-evidence-for-cannabis-qt-and-bob-bell-on-psychotherapy-globe/

9. “My brother”

Kaylynn Purdy

CMAJ, 13 September 2021

“When you meet somebody living on the streets, remember my brother.”

This is a great essay, written by a physician – and, more importantly, written by the sister of someone with major mental illness. The essay describes the life and death of her brother, who died of an overdose after struggling with major mental illness and homelessness.

It’s a moving essay. It’s also a gentle reminder of our patients’ humanity.

Dr. Purdy closes with a call to action: “I am a doctor, with the skills to save lives, yet I couldn’t save my own brother. If death was the outcome for Blake – a person with a whole family behind him, working daily to help him – how is there any hope for people who don’t have that support? To change the outcome for people like Blake – homeless, addicted and struggling with mental illness – it will take more than just a few caring individuals; it will take every member of society doing everything in their power.” Well said.

https://davidgratzer.com/reading-of-the-week/reading-of-the-week-suicidal-ideation-in-a-37-year-old-woman-a-nejm-case-also-goldbloom-on-innovation-qt-and-purdy-on-her-brother-cmaj/

10. “Realizing the Potential of Mobile Mental Health: New Methods for New Data in Psychiatry”

John Torous, Patrick Staples, Jukka-Pekka Onnela

Current Psychiatry Reports, 6 June 2015

Lacking biomarkers, our field is limited and so we gather information from interviews and observations. Could technology change this?

The authors write: “The availability of data on patient location, activity level, and social engagement provided by smartphones, among other streams of data, is unparalleled.” Since publication, much has been written about passive data and larger topics, like digital phenotyping.

Of course, we can wonder how much this will ultimately move us past our crude descriptions of mental disorders. To date, genetics hasn’t transformed psychiatric care, but will our smart phones?

https://link.springer.com/article/10.1007/s11920-015-0602-0

(The paper wasn’t covered in a past Reading, though digital technology has been mulled many times before.)

Selection 2: “Mindfulness-Based Cognitive Therapy’s Untapped Potential”

Jesus Montero-Marin, Anne Maj van der Velden, Willem Kuyken

JAMA Psychiatry, 25 September 2024  Online First

Major depressive disorder (MDD) is the second leading cause of disability worldwide, shows a 20% lifetime prevalence, can lead to premature mortality, and produces decrements in health, quality of life, and well-being, while also placing an enormous personal and economic burden on individuals, families, and societies at large. It often takes a relapsing and recurrent course; therefore, most of the prevalence, burden, and cost of depression is a consequence of relapse or recurrence… We have effective pharmacologic treatments for acute depression (eg, fluoxetine)… Many patients experience contraindications and adverse effects, and often express preferences for psychological treatments that support long-term recovery. Psychological treatments can be as effective as antidepressants, better tolerated, and associated with long-term gains at lower overall costs. Moreover, the effectiveness of combined pharmacotherapy and psychotherapy is the best practice for moderate depression.

So begins a Viewpoint by Montero-Marin et al.

“The epidemiology and life course of depression demand innovation to ensure we offer the right approach to the right person, at the right time, in the right way.” They thus see a role for mindfulness-based cognitive therapy (MBCT) which can “prevent relapse or recurrence and aid recovery…”

MBCT as an Exemplar for Innovation

“MBCT is a manualized group-based psychological program that combines mindfulness meditation practices with cognitive therapy techniques. It was designed to help individuals with recurrent depression by enhancing their awareness of and relationship to negative thoughts and feelings, thereby reducing the risk of relapse. MBCT was developed from theory and empirical findings that demonstrate the role of cognitive reactivity and rumination in the course of depression and the potential of metacognitive awareness in recognizing, decentering, and disengaging from ruminative thought patterns to prevent depressive relapse or recurrence. MBCT has demonstrated adaptability to different cultural contexts and effectiveness in countries across North America, Europe, Asia, and Australia…”

They review the literature:

  • “MBCT, compared with maintenance antidepressant medication, can significantly reduce the risk of depressive relapse by 23% within a 1-year follow-up period.”
  • “A recent meta-analysis showed that the sequential delivery of preventive cognitive therapy or MBCT during or after medication tapering may effectively prevent relapse.” 
  • “MBCT has been tested across subpopulations with depression and is considered suitable for patients with recurrent depression, irrespective of their illness stage (ie, in episode, partial remission, or full remission but vulnerable to relapse or recurrence).”

They argue it may be particularly helpful for “individuals with entrenched depression (ie, people with a history of childhood difficulties and trauma, reporting 3 or more previous MDD episodes and more residual symptoms).”

How Does MBCT Work?

“MBCT increases the capacity to adopt a decentered perspective on one’s experiences, which in turn mediates its effect on improved depression outcomes.” They draw on neuroimaging: “alterations in brain connectivity during a state of rumination can be modified by an increased ability to sustain attention on bodily sensations after receiving MBCT. This may reduce the likelihood of participants becoming stuck in ruminative processing.” 

How Can MBCT Be Accessible?

“Despite the growing evidence base and recommendations for MBCT in many national depression guidelines, access to MBCT is still limited. There are accessibility challenges for psychological treatments, such as MBCT, including costs and a shortage of psychologists.” They see a role for clinical guidelines and champions. They are also practical: “Exploring different delivery modes (eg, online platforms, blended approaches combining face-to-face sessions with digital resources, or self-help books) and MBCT-adapted programs (eg, MBCT-for-Life, or MBCT-Taking-it-Further) could enhance accessibility and reach by providing patients with various choices at different levels of intensity, potentially maximizing cost-effectiveness.”

A few thoughts:

1. This is a good Viewpoint.

2. The comment about exploring different delivery models is particularly relevant. It’s unlikely that we could train up many therapists – but online options may have a strong role, especially for those who are less ill.

3. Mindfulness is having a moment. Note, though, that the authors are discussing MBCT, not an app which promotes “mindfulness principles.”

The full JAMA Psych Viewpoint can be found here:

https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2824095



Selection 3: “Revolutionary drug for schizophrenia wins US approval”

Elie Dolgin

Nature, 27 September 2024

The first schizophrenia medication in decades with a new mechanism of action won US regulatory approval today. The approval offers the hope of an antipsychotic that would be more effective and better tolerated than current therapies.

The drug, known as KarXT, targets proteins in the brain known as muscarinic receptors, which relay neurotransmitter signals between neurons and other cells. Activating these receptors dampens the release of the chemical dopamine, a nervous-system messenger that is central to the hallmark symptoms of schizophrenia, such as hallucinations and delusions.

But muscarinic signalling also modulates other brain circuits involved in cognition and emotional processing. This mode of action provides KarXT with a more comprehensive therapeutic effect than other schizophrenia treatments, which mainly blunt dopamine activity alone.

So begins an article by Dolgin.

He describes the clinical trials. “KarXT not only alleviated core symptoms of schizophrenia, but also showed signs of improving cognitive function, all while avoiding many of the burdensome side effects commonly associated with older antipsychotics.”

“This progress is leading clinicians and drug developers to imagine a future in which schizophrenia treatment becomes more tailored to individual needs – providing an alternative for the many people who don’t benefit from current therapies or abandon them owing to intolerable side effects.”

The article notes some short-comings, including the twice daily dosing and a price tag of $20 000 per year. “Despite this, most industry analysts predict strong demand, with peak annual sales projected in the billions.”

“KarXT traces its roots back to early 1990s, when researchers at Eli Lilly in Indianapolis, Indiana, began developing xanomeline – a muscarinic-activating agent designed mainly to boost memory in people with Alzheimer’s disease, but it has been explored as a potential treatment for schizophrenia, too… Trials showed that the drug offered both antipsychotic and cognitive benefits. But xanomeline also caused nausea, vomiting and stomach pain – because muscarinic receptors are active in the gut as well as the brain – leading Lilly to ultimately shelve the drug.” The author notes that the biotech executive Andrew Miller devised a strategy to revive the therapy. “He recognized that administering the muscarinic-activating agent together with another compound that blocks xanomeline’s effects outside the brain could maintain the cognitive and antipsychotic benefits without causing severe gastrointestinal distress.”

A few thoughts:

1. Interesting.

2. The novel mechanism is very exciting. 

3. For those wanting to read more, JAMA Psychiatry published an RCT with 256 participants. We will likely return to that study in the coming weeks. In the meantime, you can find it here:

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2818047

The full Nature article can be found here:

https://www.nature.com/articles/d41586-024-03123-9

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