From the Editor

Catatonia has been well described but is poorly understood.

So write Drs. Stephan Heckers and Sebastian Walther (both of Vanderbilt University) in a new review. We could add: catatonia is often striking. I remember a patient who literally sat for hours in his chair with catatonia secondary to schizophrenia. His family, in some denial, had insisted that his poor eating was related to hospital food and that his lack of activity had to do with the boredom of the ward.

Drs. Heckers and Walther’s review, just published in The New England Journal of Medicine, notes: “Catatonia is common in psychiatric emergency rooms and inpatient units,” with an estimated prevalence of 9% to 30%. They describe the diagnosis and treatment. We consider the paper and its implications.

Waxy flexibility (from catatonia) in an undated photo

Interest in CBD has surged in recent years. Can it help with the tough clinical problem of bipolar depression? In the second selection, Dr. Jairo Vinícius Pinto (of the University of São Paulo) and his co-authors attempt to answer that question in a new Canadian Journal of Psychiatry paper. They describe a pilot study, with 35 patients randomized to CBD or placebo, finding: “cannabidiol did not show significantly higher adverse effects than placebo.”

And in the third selection, Dr. Hannah Samuels (of the University of Toronto) discusses medical assistance in dying in a paper for Academic Psychiatry. This resident of psychiatry describes a patient who, dealing with pain, opted for MAiD. Dr. Samuels considers the decision but her ambivalence in part stemming from her training. “I felt sad, confused, and morally conflicted. Mrs. L never faltered in her confidence that this was the right decision for her, but I could not understand it.”

DG

Selection 1: Catatonia”

Stephan Heckers and Sebastian Walther

The New England Journal of Medicine, 9 November 2023

Catatonia has been well described but is poorly understood. Many physicians incorrectly believe that catatonia is a rare form of schizophrenia, with bizarre abnormalities of motor behavior. Consequently, the diagnosis is often missed, and a person with catatonia may be inappropriately treated. In 2013, the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) removed catatonia as a subtype of schizophrenia and listed it as a feature of several psychiatric and medical conditions…

Despite these recent changes, there are several reasons why catatonia is often not recognized. First, its severity ranges from subtle behavioral abnormalities, lasting only hours, to malignant, at times lethal, forms. Second, the clinical features may fluctuate over variable periods of time between stupor and severe agitation, or a patient may shift from comfortable conversation to mutism that persists for hours. Patients with catatonia do not engage with their surroundings or with other people, making it difficult for the clinician to obtain a history and complete a mental status examination.

So begins a paper by Drs. Heckers and Walther.

Signs of Catatonia

They note several signs of catatonia, from those that are more frequent (staring, stupor, mutism, and posturing – see table below) to the less frequent (echolalia, echopraxia, verbigeration, and waxy flexibility).

“Catatonic signs may emerge rapidly, reaching a maximum level within hours (in acute catatonia), or may develop slowly, over a period of days or weeks. Catatonic episodes may recur periodically, or they may persist for years, as seen in some patients with schizophrenia spectrum disorders or neurodevelopmental disorders, including autism spectrum disorder. The course of catatonia due to intoxication or to other medical conditions depends on the course of the underlying condition.”

They note that several clinician-administered rating scales have been validated for catatonia, and suggest use of the Bush-Francis Catatonia Rating Scale.

Catatonia in the Emergency Department

They describe a few possible presentations:

  • “Failure to respond to questioning (mutism) and very little spontaneous movement (stupor).” They distinguish such psychomotor behaviours from delirium which has “decreased levels of alertness and cognition.”
  • “Rapidly fluctuating levels of psychomotor behavior, ranging from mutism and stupor to posturing and agitation.” They observe that this form of catatonia may be due substances (cannabis or cocaine) and advocate for a careful patient history.
  • “Rigidity accompanied by repetitive, purposeless movements, such as rocking back and forth (stereotypies).” Such a presentation is often seen in schizophrenia.

The authors note that the lorazepam challenge test is an effective treatment and validates the diagnosis.

Catatonia in the Medical Unit

“Catatonia in a patient in a medical unit requires extensive diagnostic efforts because otherwise unusual underlying causes are common in such patients. First, anti-N-methyl-d-aspartate (NMDA) receptor encephalitis may cause acute catatonia before progressing to encephalopathy or seizures. Second, several metabolic disorders and focal cerebral lesions may be manifested as catatonia. Third, catatonia may be due to prescribed or illicitly used drugs, especially in patients withdrawing from benzodiazepines, alcohol, or opioids. Fourth, in critically ill patients, catatonia may linger in the shadow of delirium because the psychomotor signs of catatonia are often not recognized in a delirious patient with fluctuating levels of attention and cognition.”

Assessment of Catatonia

“Catatonia is a clinical diagnosis, the severity of which can be captured with standardized rating scales, such as the Bush-Francis Catatonia Rating Scale, which grades 23 items, such as excitement, immobility, staring, mannerisms, and rigidity, each on a scale of 0 to 3. At a minimum, assessment of catatonia requires physical examination, including measurement of vital signs, a complete blood count, and a comprehensive blood metabolic panel.”

Treatment of Catatonia

“Management of catatonia includes specific treatments, treatment of the underlying disorder, and prevention of complications… The primary treatment of catatonia should be initiated as soon as possible after the condition has been identified, since the likelihood of a response declines with time. Both lorazepam administration… and electroconvulsive therapy (ECT) lead to a response in 60 to 100% of patients, and ECT is also effective after insufficient response to benzodiazepine administration. The lorazepam dose may be adjusted, sometimes above the standard dose (up to 16 mg per day). ECT is administered bilaterally, and effects can be expected after four to six sessions, usually administered over the course of 1 to 2 weeks. Second-line treatment of catatonia includes the NMDA receptor antagonists, amantadine and memantine.”

A few thoughts:

1. This is a clear and lucid review – essential reading. Catatonia is, after all, common if under-diagnosed.

2. The authors make good suggestions. 

3. The one I wish clinicians took seriously: use of the Bush-Francis Catatonia Rating Scale. This Scale is practical and easy to use. Measurement-based care allows us to follow a patient more objectively than simply noting that he looks better or that she is worse.

4. The author concludes that catatonia is under-researched. Is the problem that people believe catatonia is becoming less common?

The full NEJM paper can be found here:

https://www.nejm.org/doi/full/10.1056/NEJMra2116304

Selection 2: “Cannabidiol as an Adjunctive Treatment for Acute Bipolar Depression: A Pilot Study”

Jairo Vinícius Pinto, José Alexandre S. Crippa, Keila Maria Ceresér, et al.

The Canadian Journal of Psychiatry, 3 November 2023  Online First

Despite significant morbidity and mortality associated with depression in bipolar disorder, its pharmacological treatment remains challenging. For example, atypical antipsychotics such as quetiapine, lurasidone, cariprazine, and lumateperone are the only agents approved in monotherapy for treating depression in bipolar disorder, and many patients struggle with tolerability with some of these agents… Thus, development of novel, effective, and safe treatments for depression in patients with bipolar disorder is an important clinical unmet need…

Of the innovative options, cannabidiol stands out due to its effects on the endocannabinoid system, which has not been a target for any currently available treatments. Cannabidiol is one of the main phytocannabinoids present in the plant Cannabis sativa. While Δ-9-tetrahydrocannabinol (THC), the main component of cannabis, may induce anxiety and psychotic symptoms, clinical studies have supported the potential benefits of cannabidiol in the treatment of neuropsychiatric conditions such as anxiety, schizophrenia, epilepsy, and substance use disorders based on preclinical and clinical data.

So begins a paper by Pinto et al.

Here’s what they did:

“A randomized, double-blind, placebo-controlled pilot study to assess the efficacy of adjunctive cannabidiol in bipolar depression was used. Efficacy parameters were changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 8. Secondary outcomes included response and remission rates, changes in anxiety and psychotic symptoms, and changes in functioning. Patients continued double-blind treatment until week 12 to monitor for adverse effects, laboratory analysis, and manic symptoms…”

Here’s what they found:

  • “35 subjects fulfilled the study entry criteria and were randomly assigned to double-blind treatment with cannabidiol (n = 19) or placebo (n = 16).”
  • Demographics. Participants were in their 40s with the majority being female.
  • Change. “MADRS scores significantly decreased from baseline to the endpoint (placebo, −14.56; cannabidiol, −15.38), but there was no significant difference between the groups.” See figure (a) below.
  • Higher dosing. “An exploratory analysis showed a significant effect of cannabidiol 300 mg/day in reducing MADRS scores from week 2 to week 8 (placebo, −6.64; cannabidiol, −13.72).” See figure (b) below.
  • Adverse effects. “There were no significant differences in the development of manic symptoms or any other adverse effects.”

A few thoughts:

1. The topic is good, and the authors provide early data on CBD.

2. The core finding: CBD at 150 mg didn’t best placebo.

3. Was the dose too low? The authors wonder if “150 mg of cannabidiol is ineffective in treating bipolar depression as significant improvements in MADRS scores relative to placebo were seen only in patients whose dose increased to cannabidiol 300 mg daily but not in those that continued 150 mg daily.”

4. The exploratory analysis is interesting. But caution: the number of participants was low.

5. These are early days for the study of CBD in bipolar depression.

The full CJP paper can be found here:

https://journals.sagepub.com/doi/abs/10.1177/07067437231209650

Selection 3: “Reflections on Medical Assistance in Dying (MAID)”

Hannah Samuels

Academic Psychiatry, 2 November 2023  Online First

This is not a typical essay on suicide. There is nothing typical about this story or the woman whom the story is about. For confidentiality reasons, identifying information has been altered and I will refer to her as Mrs. L.

Mrs. L was a 68-year-old woman admitted to hospital in Toronto, Canada, for pain secondary to a spinal cord tumor, which caused loss of bowel and bladder function and muscle weakness. She had been living with this condition for approximately 2 years, during which time, her symptoms had worsened. She was no longer able to ambulate, and by the time I first met her, was completely bed-bound.

Her pain was severe. The first day I met her, she grimaced in agony, her smooth skin folding into a thousand tiny wrinkles. She never cried out and wasn’t always in pain, but when the pain started, the loud, animated conversation would stop suddenly and leave in its place a tangible silence.

Her request to me was simple. ‘I want to die,’ she said, ‘help me to die.’

So begins an essay by Dr. Samuels.

Noting that some 700 000 people die by suicide annually, Dr. Samuels comments: “As a psychiatry resident, these are words I hear far too often.” But she adds: “In the case of Mrs. L, however, the story was different… Mrs. L was not clearly depressed and there was no evidence of psychosis. She had never experienced suicidal ideation up until her diagnosis. She cited the pain and the inability to ambulate as the primary reason to end her life.”

Dr. Samuels reviews the legal context. “While there was room for optimization of Mrs. L’s pain medication, her goal was medical assistance in dying (MAID). In Canada, MAID is a government-approved procedure in which a person with a serious and incurable illness may be found eligible to end their suffering by physician-assisted death.”

“I struggled with her request and continued to examine her capacity to make the decision for MAID. I asked her why she preferred to die instead of optimizing her pain control. She told me that she feared cognitive dulling, a potential side effect from strong pain medication. To Mrs. L, without her mind, there was no meaning to her life.”

After learning that the patient is eligible for physician-assisted suicide, Dr. Samuels wonders: “Was I wrong to think of her desire for MAID as suicidal ideation that needed to be treated?”

“I have been trained to think of any request to die as another symptom of depression or other mental illness that can and needs to be cured. However, the story of Mrs. L made me think: When does suicidal ideation, with all its negative connotations, become an accepted MAID procedure in which doctors agree to help end another’s suffering in the most final of ways?” She also mulls the proposed legal expansion in March to those with mental disorders. “How would we as practitioners who choose to guard life above all else, cope? When does the best care mean no longer trying new treatments but instead approving and aiding in death?”

She closes by reflecting on the death. “While I write perplexed about her death, what I remember clearly is her life. Ultimately, she lived in the same way she chose to die, with freedom, dignity, and a strong sense of meaning.”

A few thoughts:

1. This is a well-written essay on a complicated topic.

2. How to understand suicidal ideation in the context of medical assistance in dying? Dr. Samuels struggles with that concept – as do many of us.

3. This topic has been considered in past Readings. Earlier this month, we looked at a Canadian Journal of Psychiatry paper on the family and patient perspectives. That Reading can be found here: 

https://davidgratzer.com/reading-of-the-week/reading-of-the-week-maid-suicide-also-ai-misinformation-and-palus-on-mental-health-merch/

The Academic Psychiatry paper can be found here:

https://link.springer.com/article/10.1007/s40596-023-01893-4

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