Catatonia Explained

Catatonia
Synonyms:Catatonic syndrome
Field:Psychiatry, neurology
Complications:Physical trauma, malignant catatonia (autonomic instability, life-threatening), dehydration, pneumonia, pressure ulcers due to immobility, muscle contractions, deep vein thrombosis (DVT)[1] and pulmonary embolism (PE)
Causes:Underlying illness (psychiatric, neurologic, or medical), brain injury/damage, certain drugs/medications
Diagnosis:Clinical, lorazepam challenge
Treatment:Benzodiazepines (lorazepam challenge), electroconvulsive therapy (ECT)
Symptoms:Immobility, mutism, staring, posturing, rigidity, low consciousness, etc.

Catatonia is a complex syndrome, most commonly seen in people with underlying mood (e.g major depressive disorder) or psychotic disorders (e.g schizophrenia).[2] [3] People with catatonia have abnormal movement and behaviors, which vary from person to person and fluctuate in intensity within a single episode. People with catatonia appear withdrawn, meaning that they do not interact with the outside world and have difficulty processing information.[4] They may be nearly motionless for days on end or perform repetitive purposeless movements. Two people may exhibit very different sets of behaviors and both still be diagnosed with catatonia. Treatment with benzodiazepines or ECT are most effective and lead to remission of symptoms in most cases.

There are different subtypes of catatonia, which represent groups of symptoms that commonly occur together. These include stuporous/akinetic catatonia, excited catatonia, malignant catatonia, and periodic catatonia.[5]

Catatonia has historically been related to schizophrenia (catatonic schizophrenia), but is most often seen in mood disorders. It is now known that catatonic symptoms are nonspecific and may be observed in other mental, neurological, and medical conditions.

Classification

Modern Classifications

The ICD-11 is the most common manual used globally to define and diagnose illness, including mental illness.[6] It diagnoses catatonia in someone who has three different symptoms associated with catatonia at one time. These symptoms are called stupor, catalepsy, waxy flexibility, mutism, negativism, posturing, mannerisms, stereotypies, psychomotor agitation, grimacing, echolalia, and echopraxia.[7] It divides catatonia into three groups based on the underlying cause; Catatonia associated with another mental disorder, catatonia induced by psychoactive substance, and secondary catatonia.

The DSM-5 is the most common manual used by mental health professionals in the United States to define and diagnose different mental illnesses. The DSM-5 defines catatonia as, “a syndrome characterized by lack of movement and communication, along with three or more of the following 12 behaviors; stupor, catalepsy, waxy flexibility, mutism, negativism, posturing, mannerism, stereotypy, agitation, grimacing, echolalia, or echopraxia.”[8] As a syndrome, catatonia can only occur in people with an existing illness. The DSM-5 divides catatonia into 3 diagnoses. The most common of the three diagnoses is Catatonia Associated with Another Mental Disorder. Around 20% of cases are caused by an underlying medical condition, and known as Catatonic Disorder Due to Another Medical Condition.[9] When the underlying condition is unknown it is considered Unspecified Catatonia.

Signs and symptoms

As discussed previously, the ICD-11 and DSM-5 both require 3 or more of the symptoms defined in the table below in order to diagnose Catatonia. However, each person can have a different set of symptoms may worsen, improve, and change in appearance throughout a single episode.[10] Symptoms may develop over hours or days to weeks.

!Symptom!Definition
StuporA marked lack of psychomotor activity; the individual appears immobile and unresponsive
CatalepsyPassive induction of a posture held against gravity
Waxy FlexibilitySlight resistance to positioning by the examiner, allowing limbs to remain in imposed positions
MutismLack of verbal response despite apparent alertness
NegativismResistance or no response to external instructions or stimuli
PosturingVoluntary assumption of inappropriate or bizarre postures
MannerismOdd, exaggerated movements or behaviors
StereotypyRepetitive, non-goal-directed movements or gestures
AgitationRestlessness or excessive motor activity without external stimulus
GrimacingFacial contortions or expressions unrelated to emotional context
EcholaliaMimicking or repeating another person’s speech
EchopraxiaMimicking or imitating another person’s movements
Because most patients with catatonia have an underlying psychiatric illness, the majority will present with worsening depression, mania, or psychosis followed by catatonia symptoms. Even when unable to interact, It should not be assumed that patients presenting with catatonia are unaware of their surroundings as some patients can recall in detail their catatonic state and their actions.[11]

Subtypes

There are several subtypes of catatonia which are used currently; Stuporous Catatonia, Excited Catatonia, Malignant Catatonia and Periodic Catatonia. Subtypes are defined by the group of symptoms and associated features that a person is experiencing or displaying. Notably, while catatonia can be divided into various subtypes, the appearance of catatonia is often dynamic and the same individual may have different subtypes at different times.[12]

Stuporous Catatonia: This form of catatonia is characterized by immobility, mutism, and a lack of response to the world around them. They may appear frozen in one position for long periods of time unable to eat, drink, or speak.

Excited Catatonia: This form of catatonia is characterized by odd mannerisms and gestures, purposeless or inappropriate actions, excessive motor activity, restlessness, stereotypy, impulsivity, agitation, and combativeness. Speech and actions may be repetitive or mimic another person's. People in this state are extremely hyperactive and may have delusions and hallucinations.[13]

Malignant Catatonia: This form of catatonia is a life threatening. It is characterized by fever, dramatic and rapid changes in blood pressure, increased heart rate and respiratory rate, and excessive sweating. Laboratory tests may be abnormal.

Periodic Catatonia: This form of catatonia is characterized by only by a person having recurrent episodes of catatonia. Individuals will experience multiple episodes over time, without signs of catatonia in between episodes. Historically, the Wernicke-Kleist-Leonhard School considered periodic catatonia a distinct form of "non-system schizophrenia" characterized by recurrent acute phases with hyperkinetic and akinetic features and often psychotic symptoms, and the build-up of a residual state in between these acute phases, which is characterized by low-level catatonic features and aboulia of varying severity.

Causes

Catatonia can only exist if a person has another underlying illness, and can be associated with a wide range of illnesses including psychiatric disorders, medical conditions, and substance use.

Psychiatric Conditions

Mood disorders such as a bipolar disorder and depression are the most common conditions underlying catatonia. Other psychiatric conditions that can cause catatonia include schizophrenia and other primary psychotic disorders,[14] autism spectrum disorders, ADHD,[15] and Post-traumatic Stress Disorder.[16] In autism, people tend to present with catatonia during periods of regression.[17]

Psychodynamic theorists have interpreted catatonia as a defense against the potentially destructive consequences of responsibility, and the passivity of the disorder provides relief.[18]

Medical Conditions

Catatonia is also seen in many medical disorders, encephalitis, meningitis, autoimmune disorders,[19] focal neurological lesions (including strokes),[20] alcohol withdrawal,[21] abrupt or overly rapid benzodiazepine withdrawal,[22] [23] [24] cerebrovascular disease, neoplasms, head injury, and some metabolic conditions (homocystinuria, diabetic ketoacidosis, hepatic encephalopathy, and hypercalcaemia).

Neurological Disorders

Catatonia can occur due to a number of neurological conditions. For instance, certain types of encephalitis can cause catatonia. Anti-NMDA receptor encephalitis is a form of autoimmune encephalitis which is known to cause catatonia in some people. Additionally encephalitis has been reported to cause catatonia in people who have encephalitis due to HIV and Herpes Simplex Virus (HSV). The research is limited, but some evidence suggests that people can develop catatonia after traumatic brain injury without a primary psychiatric disorder.[25] Similarly, there are several case reports suggesting that people have experienced catatonia after a stroke, with some people having catatonia-associated symptoms that were unexplainable by their stroke itself, and which improved after treatment with benzodiazepines.[26] [27] Parkinson disease can cause catatonia for some people by impairing their ability to produce and secrete dopamine, a neurotransmitter which is thought to contribute to motor dysfunction in people with catatonia.

Metabolic and Endocrine Disorders

Abnormal thyroid function can cause catatonia when the thyroid overproduces or underproduces thyroid hormones. This is thought to occur due to thyroid hormones impact on metabolism including in the cells of the nervous system. Abnormal electrolyte levels have also been shown to cause catatonia in rare cases. Most notably low levels of sodium in the blood can cause catatonia in some people.[28] [29] [30] [31]

Autoimmune Disorders

As discussed previously, Anti-NMDA receptor encephalitis is a form of autoimmune encephalitis which can cause catatonia. Additionally, autoimmune diseases that are not exclusively neurological can cause neurological and psychiatric symptoms including catatonia. For instance, systemic lupus erythematosus can cause catatonia and is thought to do by causing inflammation in the blood vessels of the brain or possibly by the body's own antibodies damaging neurons.

Infectious Diseases

Certain types of infections are known to cause catatonia either through directly impairing brain function or by making a person more likely to contract diseases that impair brain function. HIV and AIDS can cause catatonia, most likely by predisposing one to infections in the brain, including different types of viral encephalitis.[32] [33] Borrelia burgdorferi causes Lyme disease, which has been shown to cause catatonia by infecting the brain and causing encephalitis.[34] [35] [36] [37]

Pharmacological Causes

Use of NMDA receptor antagonists including ketamine and phencyclidine (PCP) can lead to catatonia-like states. Information about these effects has improved scientific understanding of the role of glutamate in catatonia. High dose and chronic use of stimulants like Cocaine and Amphetamines can lead to cases of catatonia, typically associated with psychosis. This is thought to be due to changes in the function of circuits of the brain associated with dopamine release.

Pathogenesis

The mechanisms in the brain that cause catatonia are poorly understood.[38] Currently, there are two main categories of explanations for what may be happening in the brain to cause catatonia. The first, is that there is disruption of normal neurotransmitter production or release in certain areas of the brain prevents normal function of those areas of the brain leading to behavioral and motor symptoms associated with catatonia. The second, claims that disruption of communication between different areas of the brain cause catatonia.

Neurotransmitters

The neurotransmitters that are most strongly associated with catatonia are GABA, dopamine, and glutamate. GABA is the main inhibitory neurotransmitter of the brain, meaning that it slows down the activity of the systems of the brain it acts on. In catatonia, people have low levels of GABA which causes them to be overly activated, especially in the areas of the brain that cause inhibition. This is thought to cause the behavioral symptoms associated with catatonia including withdrawal. Dopamine can increase or decrease the activity of the area of the brain it acts on depending on where in the brain it is. dopamine is lower than normal in people with catatonia, which is thought to cause a lot of the motor symptoms, because dopamine is the main neurotransmitter which activates the parts of the brain responsible for movement. Glutamate is an excitatory neurotransmitter, meaning that it increases the activity of the areas of the brain it acts on. Notably, glutamate increases tells the neuron it acts on to fire, by binding to the NMDA receptor. People with Anti-NMDA receptor encephalitis can develop catatonia, because their own antibodies attack the NMDA receptor, which reduces the ability of the brain to activate different areas of the brain using glutamate.

Neurological Pathways

Several pathways in the brain have been studied which seem to contribute to catatonia when they aren't functioning properly.[39] However, these studies were unable to determine if the abnormalities they observed were the cause of catatonia or if the catatonia caused the abnormalities. Furthermore, it has also been hypothesized that pathways that connect the basal ganglia with the cortex and thalamus is involved in the development of catatonia.[40]

Diagnosis

There is not yet a definitive consensus regarding diagnostic criteria of catatonia. In the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5, 2013) and the World Health Organization's eleventh edition of the International Classification of Diseases (ICD-11, 2022), the classification is more homogeneous than in earlier editions. Prominent researchers in the field have other suggestions for diagnostic criteria.[41] Still, diagnosing catatonia can be challenging. Evidence suggests that there is as high as a 15 day average delay to diagnosis for people with catatonia.

DSM-5 classification

The DSM-5 does not classify catatonia as an independent disorder, but rather it classifies it as catatonia associated with another mental disorder, due to another medical condition, or as unspecified catatonia.[42] [43]

Catatonia is diagnosed by the presence of three or more of the following 12 psychomotor symptoms in association with a mental disorder, medical condition, or unspecified:

Other disorders (additional code 293.89 [F06.1] to indicate the presence of the co-morbid catatonia):

If catatonic symptoms are present but do not form the catatonic syndrome, a medication- or substance-induced aetiology should first be considered.[44]

ICD-11 classification

In ICD-11 catatonia is defined as a syndrome of primarily psychomotor disturbances that is characterized by the simultaneous occurrence of several symptoms such as stupor; catalepsy; waxy flexibility; mutism; negativism; posturing; mannerisms; stereotypies; psychomotor agitation; grimacing; echolalia and echopraxia. Catatonia may occur in the context of specific mental disorders, including mood disorders, schizophrenia or other primary psychotic disorders, and Neurodevelopmental disorders, and may be induced by psychoactive substances, including medications. Catatonia may also be caused by a medical condition not classified under mental, behavioral, or neurodevelopmental disorders.

Assessment/Physical

Catatonia is often overlooked and under-diagnosed. Patients with catatonia most commonly have an underlying psychiatric disorder, for this reason, physicians may overlook signs of catatonia due to the severity of the psychosis the patient is presenting with. Furthermore, the patient may not be presenting with the common signs of catatonia such as mutism and posturing. Additionally, the motor abnormalities seen in catatonia are also present in psychiatric disorders. For example, a patient with mania will show increased motor activity and may not be considered for a diagnosis of Excited Catatonia, even if symptoms are developing that are not associated with mania. One way in which physicians can differentiate between the two is to observe the motor abnormality. Patients with mania present with increased goal-directed activity. On the other hand, the increased activity in catatonia is not goal-directed and often repetitive.

Catatonia is a clinical diagnosis and there is no specific laboratory test to diagnose it. However, certain testing can help determine what is causing the catatonia. An EEG will likely show diffuse slowing. If seizure activity is driving the syndrome, then an EEG would also be helpful in detecting this. CT or MRI will not show catatonia; however, they might reveal abnormalities that might be leading to the syndrome. Metabolic screens, inflammatory markers, or autoantibodies may reveal reversible medical causes of catatonia.

Vital signs should be frequently monitored as catatonia can progress to malignant catatonia which is life-threatening. Malignant catatonia is characterized by fever, hypertension, tachycardia, and tachypnea.

Rating scale

Various rating scales for catatonia have been developed, however, their utility for clinical care has not been well established.[45] The most commonly used scale is the Bush-Francis Catatonia Rating Scale (BFCRS) (external link is provided below).[46] The scale is composed of 23 items with the first 14 items being used as the screening tool. If 2 of the 14 are positive, this prompts for further evaluation and completion of the remaining 9 items.

A diagnosis can be supported by the lorazepam challenge[47] or the zolpidem challenge.[48] While proven useful in the past, barbiturates are no longer commonly used in psychiatry; thus the option of either benzodiazepines or ECT.

Laboratory Findings

Certain lab findings are common with this malignant catatonia that are uncommon in other forms of catatonia. These lab findings include: leukocytosis, elevated creatine kinase, low serum iron. The signs and symptoms of malignant catatonia overlap significantly with neuroleptic malignant syndrome (NMS). Therefore the results of laboratory tests need to be considered in the context of clinical history, review of medications, and physical exam findings.

Differential diagnosis

The differential diagnosis of catatonia is extensive as signs and symptoms of catatonia may overlap significantly with those of other conditions. Therefore, a careful and detailed history, medication review, and physical exam are key to diagnosing catatonia and differentiating it from other conditions. Furthermore, some of these conditions can themselves lead to catatonia. The differential diagnosis is as follows:

Treatment

Treating catatonia effectively requires treating the catatonia itself, treating the underlying condition, and helping them with their basic needs, like eating, drinking, and staying clean and safe, while they are withdrawn and incapable of caring for themselves.

Catatonia-Specific Treatments

The specifics of treating catatonia itself can vary from region to region, hospital to hospital, and individual to individual, but typically involves the use of benzodiazepines. In fact, in some cases it is unclear whether a person has catatonia or another condition which may present similarly. In these cases a "benzodiazepine challenge" is often done. During a "benzodiazepine challenge" a healtchare provider will give a moderate dose of a benzodiazepine to the patient and monitor them. If a person has catatonia they will often have improvements in their symptoms within 15 to 30 minutes. If the person doesn't improve within 30 minutes they're given a second dose and the process is repeated once more. If the person responds to either of the doses then they can be given benzodiazepines at a consistent dose and timing until their catatonia resolves. Depending on the person, a person may need to reduce their dosing slowly over time in order to prevent reoccurrence of their symptoms.

ECT is also commonly used to treat catatonia in people who don't improve with medication alone or whose symptoms reoccur whenever the dose of medications are reduced. ECT is usually administered with multiple sessions per week over two to four weeks.[71] ECT has a success rate of 80% to 100%.[72] ECT is effective for all subtypes of catatonia, however people who have catatonia with an underlying neurological condition show less improvement with ECT treatment.

Excessive glutamate activity is believed to be involved in catatonia;[73] when first-line treatment options fail, NMDA antagonists such as amantadine or memantine may be used. Amantadine may have an increased incidence of tolerance with prolonged use and can cause psychosis, due to its additional effects on the dopamine system. Memantine has a more targeted pharmacological profile for the glutamate system, reduced incidence of psychosis and may therefore be preferred for individuals who cannot tolerate amantadine. Topiramate is another treatment option for resistant catatonia; it produces its therapeutic effects by producing glutamate antagonism via modulation of AMPA receptors.[74]

Non-Specific Aspects of Treatment

Treating the Underlying Condition

There are many medications that are known to cause catatonia in some people including steroids, stimulants, anticonvulsants, neuroleptics or dopamine blockers. If a person has catatonia and is on these medications, they should be considered as a potential cause if another cause is not apparent and discontinued if possible.

Antipsychotics are sometimes used in those with a co-existing psychosis, however they should be used with care as they may worsen catatonia and have a risk of neuroleptic malignant syndrome, a dangerous condition that can mimic catatonia and requires immediate discontinuation of the antipsychotic. There is evidence that clozapine works better than other antipsychotics to treat catatonia.

Supportive Care

Supportive care is required in those with catatonia. This includes monitoring vital signs and fluid status, and in those with chronic symptoms; maintaining nutrition and hydration, medications to prevent a blood clot, and measures to prevent the development of pressure ulcers.

Prognosis

Twenty-five percent of psychiatric patients with catatonia will have more than one episode throughout their lives. Treatment response for patients with catatonia is 50–70%, with treatment failure being associated with a poor prognosis. Many of these patients will require long-term and continuous mental health care. The prognosis for people with catatonia due to schizophrenia is much worse compared to other causes. In cases of catatonia that develop into malignant catatonia, the mortality rate is as high as 20%.[75]

Complications

Patients may experience several complications from being in a catatonic state. The nature of these complications will depend on the type of catatonia being experienced by the patient. For example, patients presenting with withdrawn catatonia may have refusal to eat which will in turn lead to malnutrition and dehydration. Furthermore, if immobility is a symptom the patient is presenting with, then they may develop pressure ulcers, muscle contractions, and are at risk of developing deep vein thrombosis (DVT) and pulmonary embolus (PE). Patients with excited catatonia may be aggressive and violent, and physical trauma may result from this. Catatonia may progress to the malignant type which will present with autonomic instability and may be life-threatening. Other complications also include the development of pneumonia and neuroleptic malignant syndrome.

Epidemiology

Catatonia has been historically studied in psychiatric patients.[76] Catatonia is under-recognized because the features are often mistaken for other disorders including delirium or the negative symptoms of schizophrenia. The prevalence has been reported to be as high as 10% in those with acute psychiatric illnesses, and 9-30% in the setting of inpatient psychiatric care.[77] [11] The incidence of catatonia is 10.6 episodes per 100 000 person-years, which essentially means that in a group of 100,000 people, the group as a whole would experience 10 to 11 episodes of catatonia per year.[78] Catatonia can occur at any age, but is most commonly seen in adolescence or young adulthood or in older adults with existing medical conditions. It occurs in males and females in approximately equal numbers.[79] [78] Around 20% of all catatonia cases can be attributed to a general medical condition.[80] [81]

!Underlying Condition!Proportion of Catatonia Cases
Mood Disorders20-40%
Major Depressive Disorder15-20%
Bipolar Disorder15-20%
Psychotic Disorders20-30%
Schizophrenia10-15%
Schizoaffective Disorder5-10%
Autism Spectrum Disorder5-10%
Medical Conditions~20%

History

Ancient History

There have been reports of stupor-like and catatonia-like states in people throughout the history of psychiatry.[82] In ancient Greece, the first physician to document stupor-like or catatonia-like states was Hippocrates, in his Aphorisms.[83] He never defined the syndrome, but seemingly observed these states in people he was treating for melancholia. In ancient China, the first descriptions of people that appear in the Huangdi Neijing (The Yellow Emperor's Inner Canon),[84] which the book which forms the basis of Traditional Chinese Medicine. It is thought to have been compiled by many people over the course of centuries during the Warring States Period (475-221 BCE) and the early Han Dynasty (206 BCE-220 CE).

Modern History

The term “catatonia” was first used by, German psychiatrist, Karl Ludwig Kahlbaum in 1874, in his book Die Katatonie oder das Spannungsirresein, which translates to "Catatonia or Tension Insanity".[85] He viewed catatonia as its own illness, which would get worse over time in stages of mania, depression, and psychosis leading to dementia. This work heavily influenced another German psychiatrist, Emil Kraeplin, who was the first to classify catatonia as a syndrome. Kraeplin associated catatonia with a psychotic disorder called dementia praecox, which is no longer used as a diagnosis, but heavily informed the development of the concept of schizophrenia.

Kraeplin’s work influenced two other notable German psychiatrists Karl Leonhard and Max Fink and their colleagues to expand the concept of catatonia as a syndrome which could occur in the setting of many mental illnesses not just psychotic disorders. They also laid the groundwork to describe different subtypes of catatonia still used today, including Stuporous Catatonia, Excited Catatonia, Malignant Catatonia, and Periodic Catatonia. Additionally, Leonhard and his colleagues categorized catatonia as either systematic or unsystematic, based on whether or not symptoms happened according to consistent and predictable patterns. These ways of thinking shaped the way that psychologists and psychiatrists thought of catatonia well into the 20th century. In fact, catatonia was a subtype of schizophrenia as recently as the DSM-III, and wasn't revised to be able to be applied to mood disorders until 1994 with the release of the DSM-IV.

In the latter half of the 20th century, clinicians observed that catatonia occurred in various psychiatric and medical conditions, not exclusively in schizophrenia. Max Fink and colleagues advocated for recognizing catatonia as an independent syndrome, highlighting its frequent association with mood disorders and responsiveness to treatments like benzodiazepines and ECT.

Society and Culture

Popular Conceptions and Origins

Catatonia, historically misunderstood, has been subject to shifting perceptions in society. As discussed previously, since the 19th century it was often linked exclusively to schizophrenia, perpetuating misconceptions. These historical misunderstandings have shaped the public opinions on catatonia. This has contributed to a lack of understanding about catatonia and its broader association with other mental disorders and medical conditions.

Popular culture and media have played a significant role in shaping societal perceptions of catatonia. In many cases, media portrayals reduce it to a stereotypical "frozen state," similar to a coma, failing to capture the complexity of symptoms like stupor, agitation, and mutism. Such oversimplifications contribute to public misperceptions and get in the way of people receiving the care they need.

See also

External links

Notes and References

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