Catatonia

Catatonia is a neuropsychiatric behavioral syndrome that is characterized by abnormal movements, immobility, abnormal behaviors, and withdrawal.

Although catatonia has historically been related to schizophrenia (catatonic schizophrenia), catatonia is most often seen in mood disorders. It is now known that catatonic symptoms are nonspecific and may be observed in other mental, neurologic, and medical conditions. Catatonia is not a stand-alone diagnosis (although some experts disagree), and the term is used to describe a feature of the underlying disorder.

The onset of catatonia can be acute or subtle and symptoms can wax, wane, or change during episodes. There are several subtypes of catatonia: retarded catatonia, excited catatonia, malignant catatonia, and other forms.

Recognizing and treating catatonia is very important as failure to do this can lead to poor outcomes and can be potentially fatal. Treatment with benzodiazepines or ECT can lead to remission of catatonia. There is growing evidence of the effectiveness of the NMDA receptor antagonists amantadine and memantine for benzodiazepine-resistant catatonia. Antipsychotics are sometimes employed, but they can worsen symptoms and have serious adverse effects.

History

It was first described in 1874 by Karl Ludwig Kahlbaum as Die Katatonie oder das Spannungsirresein (Catatonia or Tension Insanity).

Etiology/Causes

In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), catatonia is not recognized as a separate disorder. Catatonia is often the result of an underlying disease which can be psychiatric or medical. Furthermore, treatments for these underlying disorders may cause or worsen catatonia.

When catatonic symptoms are present, the cause is usually psychiatric with mood disorders including bipolar disorder and major depressive disorder being the most common culprits. Schizophrenia has been historically associated with catatonia. Other psychiatric associations include schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, and substance-induced psychotic disorder. It appears as the Kahlbaum syndrome (motionless catatonia), malignant catatonia (neuroleptic malignant syndrome, toxic serotonin syndrome), and excited forms (delirious mania, catatonic excitement, oneirophrenia). It also is related to autism spectrum disorders.

Although the cause of catatonia is usually psychiatric in nature, it may also be seen in many medical disorders, including infections (such as encephalitis), autoimmune disorders, meningitis, focal neurological lesions (including strokes), alcohol withdrawal, abrupt or overly rapid benzodiazepine withdrawal, cerebrovascular disease, neoplasms, head injury, and some metabolic conditions (homocystinuria, diabetic ketoacidosis, hepatic encephalopathy, and hypercalcaemia).

Epidemiology

Catatonia has been mostly studied in acutely ill psychiatric patients. Catatonia frequently goes unrecognized, leading to the belief that the syndrome is rare, however, this is not true and prevalence has been reported to be as high as 10% in patients with acute psychiatric illnesses.

Pathogenesis/Mechanism

The pathophysiology that leads to catatonia is still poorly understood and a definite mechanism remains unknown. Neurologic studies have implicated several pathways, however, it remains unclear whether these findings are the cause or the consequence of the disorder.

Abnormalities in GABA, glutamate signaling, serotonin, and dopamine transmission are believed to be implicated in catatonia.

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.

Signs and symptoms

The presentation of a patient with catatonia varies greatly depending on the subtype, underlying cause and it can be acute or subtle.

Because most patient’s with catatonia have an underlying psychiatric illness, most patients will present with worsening depression, mania, or psychosis followed by catatonia symptoms. Catatonia presents as a motor disturbance in which patients will display marked reduction in movement, marked agitation, or a mixture of both despite having the physical capacity to move normally. These patients may be unable to start an action or stop one. Movements and mannerisms may be repetitive, or purposeless.

The most common signs of catatonia are immobility, mutism, withdrawal and refusal to eat, staring, negativism, posturing (rigidity), rigidity, waxy flexibility/catalepsy, stereotypy (purposeless, repetitive movements), echolalia or echopraxia, verbigeration (repeat meaningless phrases). 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.

There are several subtypes of catatonia and they are characterized by the specific movement disturbance and associated features. Although catatonia can be divided into various subtypes, the natural history of catatonia is often fluctuant and different states can exist within the same individual.

Subtypes

Retarded/Withdrawn Catatonia: This form of catatonia is characterized by decreased response to external stimuli, immobility or inhibited movement, mutism, staring, posturing, and negativism. Patients may sit or stand in the same position for hours, may hold odd positions, and may resist movement of their extremities.

Excited Catatonia: Excited catatonia is characterized by odd mannerisms/gestures, performing purposeless or inappropriate actions, excessive motor activity restlessness, stereotypy, impulsivity, agitation, 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. Catatonic excitement is commonly cited as one of the most dangerous mental states in psychiatry.

Malignant Catatonia: Malignant catatonia is a life-threatening condition that that may progress rapidly within a few days. It is characterized by fever, abnormalities in blood pressure, heart rate, respiratory rate, diaphoresis (sweating), and delirium. Certain lab findings are common with this presentation, however, they are nonspecific which means that they are also present in other conditions and do not diagnose 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) and so a careful history, review of medications, and physical exam are critical to properly differentiate these conditions. For example, if the patient has waxy flexibility and holds a position against gravity when passively moved into that position, then it is likely catatonia. If the patient has a “lead-pipe rigidity” then NMS should be the prime suspect.

Diagnosis

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

• stupor: no psycho-motor activity; not actively relating to environment
• catalepsy: passive induction of a posture held against gravity
• waxy flexibility: allowing positioning by examiner and maintaining that position
• mutism: no, or very little, verbal response (exclude if known aphasia)
• negativism: opposition or no response to instructions or external stimuli
• posturing: spontaneous and active maintenance of a posture against gravity
• mannerisms that are odd, circumstantial caricatures of normal actions
• stereotypy: repetitive, abnormally frequent, non-goal-directed movements
• agitation, not influenced by external stimuli
• grimacing: keeping a fixed facial expression
• echolalia: mimicking another's speech
• echopraxia: mimicking another's movements.

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

• Catatonia associated with autism spectrum disorder
• Catatonia associated with schizophrenia spectrum and other psychotic disorders
  • Catatonia associated with brief psychotic disorder
  • Catatonia associated with schizophreniform disorder
  • Catatonia associated with schizoaffective disorder
  • Catatonia associated with substance-induced psychotic disorder
• Catatonia associated with bipolar and related disorders
• Catatonia associated with major depressive disorder
• Catatonic disorder due to another medical condition

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

Rating scale

Various rating scales for catatonia have been developed. The most commonly used scale is the Bush-Francis Catatonia Rating Scale (BFCRS). A diagnosis can be supported by the lorazepam challenge or the zolpidem challenge. While proven useful in the past, barbiturates are no longer commonly used in psychiatry; thus the option of either benzodiazepines or ECT.

Treatment

Initial treatment is aimed at providing symptomatic relief. Benzodiazepines are the first line of treatment, and high doses are often required. A test dose of intramuscular lorazepam will often result in marked improvement within half an hour. In France, zolpidem has also been used in diagnosis, and response may occur within the same time period. Ultimately the underlying cause needs to be treated.

Electroconvulsive therapy (ECT) is an effective treatment for catatonia, however, it has been pointed out that further high quality randomized controlled trials are needed to evaluate the efficacy, tolerance, and protocols of ECT in catatonia.

Antipsychotics should be used with care as they can worsen catatonia and are the cause of neuroleptic malignant syndrome, a dangerous condition that can mimic catatonia and requires immediate discontinuation of the antipsychotic.

Excessive glutamate activity is believed to be involved in catatonia; 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.

Outcomes and Recurrence

Patients who experience an episode of catatonia are more likely to suffer recurrence.

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:

--Neuroleptic malignant syndrome (NMS): Malignant catatonia and NMS are both life-threatening conditions that share many of the same characteristics including fever, autonomic instability, rigidity, and delirium. Lab values of low serum iron, elevated creatine kinase, and white blood cell count are also shared by the two disorders further complicating the diagnosis. Some experts consider NMS a drug-induced form of catatonia, however, it has not been established as a subtype. There are features of malignant catatonia (posturing, impulsivity, etc) that are absent from NSM and the lab results are not as consistent in malignant catatonia as they are in NMS. NMS is a drug-induced condition associated with antipsychotics, particularly, first generation antipsychotics. Therefore, discontinuing antipsychotics and starting benzodiazepines is a treatment for this condition, and similarly it is helpful in catatonia as well.

--Anti-NMDA receptor encephalitis: Anti-NMDA receptor encephalitis is an autoimmune disorder characterized by neuropsychiatric features and the presence of IgG antibodies. The presentation of anti-NMDAR encephalitis has been categorized into 5 phases: prodromal phase, psychotic phase, unresponsive phase, hyperkinetic phase, and recovery phase. The psychotic phase progresses into the unresponsive phase characterized by mutism, decreased motor activity, and catatonia.

--Serotonin syndrome: Both serotonin syndrome and malignant catatonia may present with sings and symptoms of delirium, autonomic instability, hyperthermia, and rigidity. Again, similar to the presentation in NSM. However, patients with Serotonin syndrome have a history of ingestion of serotonergic drugs (Ex: SSRI). These patients will also present with hyperreflexia, myoclonus, nausea, vomiting, and diarrhea.

--Malignant hyperthermia: Malignant hyperthermia and malignant catatonia share features of autonomic instability, hyperthermia, and rigidity. However, malignant hyperthermia is a hereditary disorder of skeletal muscle that makes these patients susceptible to exposure to halogenated anesthetics and/or depolarizing muscle relaxants like succinylcholine. Malignant hyperthermia most commonly occurs in the intraoperative or postoperative periods. Other signs and symptoms of malignant hyperthermia include metabolic and respiratory acidosis, hyperkalemia, and cardiac arrhythmias.

--Akinetic mutism: Akinetic mutism is a neurological disorder characterized by a decrease in goal-directed behavior and motivation, however, the patient has an intact level of consciousness. Patients may present with apathy, and may seem indifferent to pain, hunger, or thirst. Akinetic mutism has been associated with structural damage in a variety of brain areas. Akinetic mutism and catatonia may both manifest with immobility, mutism, and waxy flexibility. Differentiating both disorders is the fact that akinetic mutism does not present with echolalia, echopraxia, or posturing. Furthermore, it is not responsive to benzodiazepines as is the case for catatonia.

--Elective mutism: Elective mutism has an anxious etiology but has also been associated with personality disorders. Patients with this disorder fail to speak with some individuals but will speak with others. Likewise, they may refuse to speak in certain situations, for example, a child who refuses to speak at school but is conversational at home. This disorder is distinguished from catatonia by the absence of any other sings/symptoms.

--Nonconvulsive status epilepticus: Nonconvulsive status epilepticus is seizure activity with no accompanying tonic-clonic movements. It can present with stupor, similar to catatonia, and they both respond to benzodiazepines. Nonconvulsive status epilepticus is diagnosed by the presence of seizure activity seen on electroencephalogram (EEG). Catatonia on the other hand, is associated with normal EEG or diffuse slowing.  

--Delirium: Delirium is characterized by fluctuating disturbed perception and consciousness in the ill individual. It has hypoactive and hyperactive or mixed forms. People with hyperactive delirium present similarly to those with excited catatonia and have symptoms of restlessness, agitation and aggression. Those with hypoactive delirium present with similarly to retarded catatonia, withdrawn and quiet. However, catatonia also includes other distinguishing features including posturing and rigidity as well as a positive response to benzodiazepines.

--Locked-in syndrome: Patients with locked-in syndrome present with immobility and mutism, however, unlike patients with catatonia who are unmotivated to communicate, patients with locked-in syndrome try to communicate with eye movements and blinking. Furthermore, locked-in syndrome is caused by damage to the brainstem.

--Stiff-person syndrome: Catatonia and stiff-person syndrome are similar in that they may both present with rigidity, autonomic instability and a positive response to benzodiazepines. However, stiff-person syndrome may be associated with anti-glutamic acid decarboxylase (anti-GAD) antibodies and other catatonic signs such as mutism and posturing are not part of the syndrome.

--Parkinson's disease: Untreated late-stage Parkinson’s disease may present similarly to retarded catatonia with symptoms of immobility, rigidity, and difficulty speaking. Further complicating the diagnosis is the fact that many patients with Parkinson’s disease will have major depressive disorder which may be the underlying cause of catatonia. Parkinson’s disease can be distinguished from catatonia by a positive response to levodopa. Catatonia on the other hand will show a positive response to benzodiazepines.

See also