From the Editor

I started seeing him after his psychiatrist retired. For the most part, our interactions were unremarkable: quick visits when we would talk about his walks, and then I would offer a prescription. Imagine my surprise when I heard that he had been admitted to the ICU with fever, rigidity, and decreased consciousness.

Neuroleptic malignant syndrome, what my patient developed, is rare and potentially deadly. What’s the DSM description? The differential? What are the implications for future treatment? In the first selection, Drs. Eelco F. M. Wijdicks and Allan H. Ropper (both of the Mayo Clinic Hospital) provide a concise and lucid review for The New England Journal of Medicine. They summarize the literature and offer practical suggestions. “Neuroleptic malignant syndrome is a distinctive and alarming syndrome that occurs in some persons who have been exposed to dopamine-blocking agents, particularly (but not exclusively) antipsychotic drugs.” We discuss the review and its takeaways.

How much of primary care is focused on mental healthcare? In the second selection, Avshalom Caspi (of the University of Oslo) and his co-authors attempt to answer that question, drawing on Norwegian data. In a new study for Nature Mental Health, they analyzed 350 million contacts with primary care (yes, you read that correctly) over a 14-year period. “One out of every 8 or 9 encounters that a primary care physician is for a mental-health concern.”

In the third selection, Lucy Foulkes (of the University of Oxford) writes about mental health awareness efforts. While focusing on the UK, her comments are relevant here, with campaigns by Bell Canada and others. She raises several objections, including that these efforts aren’t matched by improved access to care. “We do not have clear evidence about the impact of mental health awareness efforts. It may be that these efforts are merely a waste of time or that they are actively harmful. Or it may be that despite the above concerns, there is still a net gain that makes the efforts worthwhile.”

DG

Selection 1: “Neuroleptic Malignant Syndrome”

Eelco F. M. Wijdicks and Allan H. Ropper

The New England Journal of Medicine, 25 September 2024

The introduction of chlorpromazine in the mid-1950s, which represented a new class of antipsychotic drugs, marked a major advance in psychiatric care. Named ‘neuroleptics’ – from the Greek neuron (nerve) and lepsis (to seize) – these compounds were discovered incidentally as part of a search for adjuncts to general anesthetics and analgesics. Neuroleptic drugs block or alter central nervous system dopamine and have become a principal form of treatment for psychosis and, in particular, for schizophrenia…

High-potency, first-generation (typical) antipsychotic agents such as haloperidol, fluphenazine, and pimozide have most often been implicated in cases of neuroleptic malignant syndrome, but these agents are still used, in part because they are effective and are less expensive than newer antipsychotic drugs. In a report based on an Australian database of adverse drug reactions, the syndrome occurred with both first-generation and second-generation (atypical) drugs, and second-generation drugs were associated with a low incidence of the disorder.

So begins a review by Drs. Wijdicks and Ropper.

On the DSM Criteria

“The Diagnostic and Statistical Manual of Mental Disorders, fifth edition, criteria for the diagnosis of neuroleptic malignant syndrome include exposure to a dopamine-blocking drug, severe muscular rigidity, fever, and at least two of the following features: diaphoresis, dysphagia, tremor, incontinence, an altered level of consciousness, mutism, tachycardia, elevated or labile blood pressure, leukocytosis, or an elevated serum creatine kinase level…”

On the Typical Presentation

“The typical presentation of neuroleptic malignant syndrome is dysautonomia, particularly tachycardia and rapidly fluctuating hypertensive or hypotensive blood pressure; temperature elevation to 40°C or higher; delirium that in the severe form is catatonia; and increased muscle tone. Blood-pressure alterations and muscle hypertonicity are usually the first signs of the disorder, although some reports have emphasized early behavioral features. The muscular rigidity has been described in various ways, but it is essentially an extrapyramidal ‘lead pipe’ sign that is perceived by the examiner as uniform resistance to movement through a range of passive motion of a limb and that can be haptically differentiated from spasticity, dystonia, and spasm. A cogwheel phenomenon may interrupt the rigidity, as it does in Parkinson’s disease, but whether this is a parkinsonian effect of the causative drug or an essential feature of the rigidity that characterizes neuroleptic malignant syndrome is not clear.”

On the Differential

“With respect to the differential diagnosis of neuroleptic malignant syndrome, pedagogic exercises emphasize consideration of acute serotonin syndrome, since it may cause acute dysautonomia, but hyperreflexia, clonus, myoclonus, and shivering, which characterize serotonin syndrome, are not components of neuroleptic malignant syndrome. The muscular salience in serotonin syndrome is closer to spasticity than to the lead-pipe rigidity of neuroleptic malignant syndrome, and hyperreflexia is characteristic of serotonin syndrome, in contrast to the diminished or normal tendon reflexes in neuroleptic malignant syndrome.”

On the Treatment

“Management of neuroleptic malignant syndrome, like the management of any other critical illness, requires close clinical attention and a focus on risk factors for complications and death. In addition to withdrawal of the offending agent when possible, treatment involves a tiered approach to the main features of the syndrome: blood-pressure instability, hyperthermia and rhabdomyolysis from severe rigidity, and the potential for respiratory compromise. Data from prospective trials of the currently used interventions are lacking, and there may be several effective approaches.

“A suggested approach to critical care management is shown in the figure.” 

On Outcomes

“Recovery times vary but generally range from 7 to 11 days and may be roughly predicted from the half-life of the implicated neuroleptic drug. The relative effects of different treatments on outcome have been estimated by comparing the amount of time required for complete recovery –for example, a mean of 15 days with supportive care as compared with 9 days with dantrolene and 10 days with bromocriptine. In a case–control analysis based on published reports, mortality appeared to be lower among patients treated with dopaminergic drugs than among those who were not treated with these agents.”

A few thoughts:

1. This is an excellent review.

2. It’s also very practical.

3. Here are five takeaways from the big review:

  • It’s rare – but it happens. Indeed, just one dose of an antipsychotic could lead to NMS.
  • Clinical criteria vary but it is described in DSM-5 and remember: “In practice, the syndrome is easier to identify than this list of items suggests.”
  • Serotonin syndrome is on the differential – but it’s quite different (and includes hyperreflexia, clonus, myoclonus, and shivering).
  • Treatment of NMS is complicated and often includes an ICU admission.
  • NMS complicates post-syndrome treatment. “After the offending agent (or agents) is discontinued, it is typically not reintroduced. This may make it difficult to control the underlying disorder for which the agent was used.”

The full NEJM review can be found here:

https://www.nejm.org/doi/full/10.1056/NEJMra2404606

Selection 2: “A nationwide analysis of 350 million patient encounters reveals a high volume of mental-health conditions in primary care”

Avshalom Caspi, Renate M. Houts, Terrie E. Moffitt, et al.

Nature Mental Health, 19 September 2024

Primary-care physicians (PCPs) are important providers in many healthcare systems. PCPs treat all common health conditions, both acute and chronic; they provide preventive care and health education to patients; and they refer some patients to specialist treatment. Although many PCPs feel ill-equipped to deliver care that is the province of psychiatric services, they are often the first point of contact for navigating mental-health care. Current efforts to strengthen primary care aim to address mental health and make whole-person care a reality…

How much of PCPs’ work is devoted to addressing mental-health conditions? The available information can be confusing. For example, a report from the American Psychological Association claims that ‘as many as 70% of primary-care visits are driven by patients’ psychological problems’ and a survey carried out by the UK charity Mind reports that 40% of PCPs’ appointments involve mental health. Some of the most thorough data about the volume of mental-health concerns addressed in primary-care visits come from the National Ambulatory Medical Care Surveys, which provide information about care provision in the United States obtained via physician surveys. These data indicate that the percent of primary-care visits with a mental-health concern as a primary diagnosis increased from 3.4% of visits in 2006–2007 to 6.3% by 2016–2018. However, these data have some limitations. The survey response rate is variable (<50% in 2018); the care-provision observation window is a randomly selected 1-week reporting period; and the information is restricted to patients over age 18 years.

So begins a paper by Caspi et al.

Here’s what they did:

  • They drew on Norway’s nationwide administrative primary-care records.
  • They analyzed patient encounters over a 14-year period (2006 to 2019) including children, adults, and geriatrics; encounters had been recorded with the International Classification of Primary Care.
  • They used the data to estimate “(a) how much of PCPs’ work is devoted to addressing mental health, (b) the volume of the different types of mental-health conditions that PCPs are called on to address, (c) the volume of mental-health conditions that PCPs address at different stages of their patients’ lifespan, and (d) to compare estimates of PCPs’ mental-health encounters against estimates of encounters for other medical conditions…”

Here’s what they found:

  • A total of 4 875 722 patients generated 354 516 291 encounters. 
  • Encounters. One in nine encounters (11.7%) involved a mental-health condition. (!!)
  • Conditions. “Of the 41,616,704 mental-health encounters, over one-third involved depression (23.8%) or anxiety (14.1%), followed by sleep disturbances (12.1%), substance abuse (8.3%), acute stress reactions (7.1%), psychosis (6.9%), dementia/memory problems (5.4%), ADHD (3.8%), phobias/compulsive disorders (1.7%), developmental delay/learning problems (1.5%), PTSD (1.3%) and personality disorder (1.1%).”
  • Age. “Primary-care physicians frequently treat complex mental-health conditions in patients of every age.” See figure below.
  • Share. “Only musculoskeletal conditions accounted for a greater share of primary-care physicians’ attention.” 
  • Volume. “The volume of mental-health encounters in primary care equaled encounters for infections, cardiovascular and respiratory conditions and exceeded encounters for pain, injuries, metabolic, digestive, skin, urological, reproductive and sensory conditions.”

A few thoughts:

1. This is an impressive study – with a robust dataset (including hundreds of millions primary care contacts) over 14 years.

2. The main finding: mental health conditions were a major reason for primary care contacts (about 11% of all visits).

3. There is much to like about this study. The dataset included an entire nation. As well, Norway assigns people to family doctors – meaning that there were no selection biases.

4. An obvious limitation here is that the data is only from Norway, but the main finding is comparable to those found in (much smaller) Canadian and American studies.

5. Perspective: as hard as we work in mental health, the majority of mental healthcare is delivered by primary care docs.

The full paper can be found here:

https://www.nature.com/articles/s44220-024-00310-5

Selection 3: “The problem with mental health awareness”

Lucy Foulkes

The British Journal of Psychiatry, 14 October 2024

In the past 15 years, considerable amounts of money and time have been spent on mental health awareness efforts in the UK. These include campaigns run by public health bodies and charities as well as initiatives run by workplaces, universities and schools. These efforts promote a variety of content, such as explaining symptoms, destigmatising specific disorders, stating that mental health problems are common and encouraging people to seek help. Thousands of social media accounts run by clinicians or lay people promote similar messages. The overarching aim of these efforts is to convey that anyone can experience problems with their mental health, that this should not be stigmatised, and that help is available if people seek it.

On the face of it, these are important, useful messages to disseminate. Some people will undoubtedly have benefited from this shift in public discourse, and there is evidence that stigma has reduced since awareness campaigns began. However, beneath the surface, there are a number of issues with mental health awareness efforts, which mean that in some cases they may be unhelpful and perhaps even actively harmful.

So begins a letter by Foulkes.

She writes about three issues she has with such efforts.

Mental health awareness efforts have not been matched by improved access to treatment

“Referrals and waiting lists for mental health services continue to increase, particularly among young people. These increases are probably due to a combination of factors: more people experiencing symptoms, more people seeking help and/or reduced funding to services. Whatever the explanation, the upshot is the same: people are being told to seek help and the help is often not there. If someone is made aware that they are experiencing mental health problems or are encouraged to view their distress in this way, and they ask for help only to be told there is none, this may exacerbate their distress.”

Mental health awareness efforts may encourage overpathologising

“To start, some mental health problems are responses to exceptionally difficult external circumstances (e.g. poverty, bullying). Many awareness campaigns aim to empower individuals to improve their symptoms by changing the way they think and behave, but this message can inaccurately imply that individuals are the root cause of their symptoms, ignoring systemic hardships and societal issues that need addressing instead.”

She also notes that “overpathologising can become a self-fulfilling prophecy.” She argues that: “There is extensive evidence that when individuals are encouraged to notice or label unpleasant symptoms, these symptoms can increase. There is emerging evidence that viewing mental health awareness materials can affect how people interpret and report their own symptoms.” 

Mental health awareness efforts may alienate the very people they were originally trying to support

“Individuals with the most severe mental health problems feel they have been left out of the public conversation, with all the oxygen taken up by individuals who have milder symptoms, and they feel that their debilitating disorders are being misrepresented and dismissed.”

A few thoughts:

1. This is a well-written letter.

2. Foulkes isn’t the first to raise concerns, of course. That said, her argument is solid and nuanced.

3. Dr. Niall Boyce (of the Wellcome Foundation) writes on social media: “At the very least, we have to ask: are awareness campaigns shifting people’s perceptions to meet the reality of mental health problems, or shifting reality to meet people’s perceptions?” Good point.

4. To play devil’s advocate: given the heavy stigmatization of mental illness, aren’t public campaigns essential to allow people to feel more comfortable starting conversations with family and health providers?

The full BJP letter can be found here:

https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/problem-with-mental-health-awareness/589DD872C331A27DAB145279579B9E5A


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