Catatonia

Last edited on November 23, 2023

Catatonia is a severe heterogeneous neuropsychiatric and medical syndrome with motor and/or behavioural signs. At times, it can be life-threatening, especially in its malignant form when complicated by fever and autonomic disturbances. Catatonia is not just a psychiatric syndrome and can accompany both psychiatric and medical illnesses.

History

Catatonia was first identified as a syndrome in 1874 by German psychiatrist Karl Ludwig Kahlbaum.^[1]

Epidemiology

Catatonia is typically diagnosed in an inpatient setting, and can occur in up to 35% of individuals with schizophrenia.
The prevalence of catatonia is difficult to estimate.
- There is an estimated prevalence between 2-9% in consultation-liaison settings, between 7-17% in inpatients with psychosis, and 15-31% in individuals with mood disorders.
- It is under-recognized in pediatric and autism populations.^[2]

Prognosis

Patients with hypoactive or decreased psychomotor activity (the most common type of catatonia) can have impaired swallowing, dehydration, malnourishment from lack of eating, and risk of aspiration.
There is also a higher risk for sequelae from immobilization such as DVTs, PEs, contractures, and pressure ulcers.
Although catatonia can be severe and life-threatening, non-malignant catatonia generally has a good prognosis.

Comorbidity

Historically, catatonia was attributed most commonly to psychotic disorders. However, the majority of catatonia actually involve patients with depressive or bipolar disorders. Neurodevelopmental disorders (e.g. - autism) are also common, and up to 10% of individuals with autism spectrum disorders can experience catatonia. ^[3]
More importantly, catatonia is not just a psychiatric syndrome, and can be caused by a variety of other medical conditions such as encephalitis, lupus, and traumatic brain injuries.

Risk Factors

Prior episodes of catatonia, current or past extrapyramidal symptoms, mood disorders with psychomotor changes, autism spectrum disorder, psychotropic medications (antipsychotics, antidepressants), substances (cocaine use, or alcohol/benzodiazepine withdrawal), withdrawal of long-term anticholinergic use, electrolyte disturbances (hyponatremia, hypomagnesemia, and low serum iron) are risk factors for developing catatonia.^[4]
Additional risk factors include central nervous system disease (frontal, basal ganglia, brainstem, pontine, or cerebellar), epilepsy, dehydration, weight loss, and medications that lower seizure threshold.^[5]

Catatonia can be classified under 1 of 3 categories under the DSM-5:

Catatonia Associated With Another Mental Disorder (e.g. - marked psychomotor disturbance in neurodevelopmental, psychotic, bipolar, depressive, or other mental disorder)
Catatonic Disorder Due to Another Medical Condition (e.g. - encephalitis, traumatic brain injury, etc.)
Unspecified Catatonia

Only Criterion A needs to be met to have a diagnosis of Catatonia Associated With Another Mental Disorder (Catatonia Specifier)

Criterion A

The clinical picture is dominated by at least 3 of the following symptoms:

Stupor (i.e. - no psychomotor activity; not actively relating to environment)
Catalepsy (i.e. - passive induction of a posture held against gravity; or muscular rigidity and fixity of posture regardless of external stimuli; catalepsy is a motor symptom of schizophrenia similar to waxy flexibility)
Waxy flexibility (i.e. - slight, even resistance to positioning by examiner; the limb can be placed in an awkward posture and remain fixed in position for long time despite asking the individual to relax)
Mutism (i.e. - no, or very little, verbal response [exclude if known aphasia])
Negativism (i.e. - opposition or no response to instructions or external stimuli; see also Gegenhalten)
Posturing (i.e. - spontaneous and active maintenance of a posture against gravity)
Mannerism (i.e. - odd, circumstantial caricature of normal actions)
Stereotypy (i.e. - repetitive, abnormally frequent, non-goal-directed movements)
Agitation (not influenced by external stimuli)
Grimacing
Echolalia (i.e. - mimicking another’s speech)
Echopraxia (i.e. - mimicking another’s movements)

Mnemonic

The mnemonic WRENCHES can be used to remember the core features of catatonia:

W - Waxy flexibility
R - Rigidity
E - Echopraxia
N - Negativism
C - Catalepsy
H - High level of motor activity
E - Echolalia
S - Stupor, Stereotypy

Criterion A, B, C, D, and E must ALL be met to have a diagnosis of Catatonic Disorder Due to Another Medical Condition

Criterion B

There is evidence from the history, physical examination, or laboratory findings that the disturbance is the direct pathophysiological consequence of another medical condition.

Criterion C

The disturbance is not better explained by another mental disorder (e.g. - a manic episode).

Criterion D

The disturbance does not occur exclusively during the course of a delirium.

Criterion E

The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Memory Aid

If you don't like the WRENCHES mnemonic, catatonia can also be remembered by breaking it down into the categories of decreased, increased, and abnormal psychomotor activity:

Decreased Behaviours
- Stupor
- Negativism
- Mutism
- Posturing
- Catalepsy
Abnormal Behaviours
- Stereotypy
- Mannerism
- Waxy flexibility
- Echolalia
- Echopraxia
Increased Behaviours
- Agitation
- Grimacing

See also: Tandon, R. et al. (2013). Catatonia in DSM-5. Schizophrenia research, 150(1), 26-30.

The DSM-5 lists a total of 12 symptoms of catatonia, but there are actually more than 12 symptoms of catatonia!^[6]
- The Bush-Francis Scale measures the non-DSM criteria, including: verbigeration, withdrawal, mitgehen, gegenhalten, gasp reflex, automatic obedience, ambitendency, autonomic abnormality, and combativeness.
Patients can have various clusters of signs and symptoms including decreased psychomotor activity (mute, staring, immobile), abnormal motor movements (grasp, echolalia phenomena, rigidity) or increased psychomotor activity (agitation, impulsivity, combativeness).
Catatonia can also be periodic with episodes of relapse and remission, with mild residual symptoms.

Three subtypes of catatonia have been categorized: stuporous, excited, and malignant. It should be noted that these subtypes are not recognized in the DSM-5.

Stuporous catatonia is characterized by immobility, staring, mutism, rigidity, withdrawal and refusal to eat, along with more bizarre features such as posturing, grimacing, negativism, waxy flexibility, echophenomena, stereotypy, verbigeration, and automatic obedience.
Excited catatonia is characterized by purposeless and excessive motor activity that includes disorganized pressured speech, flight of ideas, verbigeration, disorientation and/or confusion, and confabulation.
Malignant catatonia is accompanied by fever and dysautonomia, and associated with increased morbidity and mortality (up to 10% mortality). Neuroleptic malignant syndrome is one form of malignant catatonia. Delirious mania is another form of malignant catatonia, and has features of both excited and malignant catatonia.

See also article: Neuroleptic Malignant Syndrome (NMS)

Malignant catatonia is a life threatening form of catatonia and requires rapid treatment with Electroconvulsive Therapy (ECT). Malignant catatonia presents with typical catatonia features along with fever and dysautonomia.
- Neuroleptic Malignant Syndrome (NMS) is thought to be an iatrogenic variant of malignant catatonia.
- Remember again that NMS is caused by excessive dopamine bloackade from dopamine antagonists (typically antipsychotics) or withdrawal of a dopamine agonist or GABA-A agonist.
- The mortality rate for malignant catatonia is close to 10%.
Complications of malignant catatonia include acute renal insufficiency, respiratory distress syndrome, aspiration, pneumonia, bowel pseudo-obstruction, burns, cachexia, cardiac arrest, Cheynes-Stokes breathing, deep vein thrombosis, dehydration, dysphagia, diffuse intravascular coagulation (DIC), gastrointestinal bleeding, hepatocellular damage, hypoglycemia, laryngospasm, myocardial infarction, necrotizing enterocolitis, pneumonia, pulmonary emboli, respiratory arrest, rhabdomyolysis, seizures, sepsis, and urinary retention.

Psychometric Scales for Catatonia

Name	Rater	Description	Download
Bush-Francis Catatonia Rating Scale (BFCRS)	Patient	The screening section marks items #1-14 as either “absent” or “present.” The full scale rates items #1-23 on a scale of 0-3. The ratings are made based on the observed behaviors during the examination, with the exception of completing the items for “withdrawal” and “autonomic abnormality,” which may be based upon either observed behaviours and/or chart documentation. Rate items only if well defined. If uncertain, rate the item as “0”.^[7]	Download BFCRS

Medical Illness

A variety of medical conditions may cause catatonia, especially neurological conditions (e.g. - neoplasms, head trauma, cerebrovascular disease, encephalitis) and metabolic conditions (e.g. - hypercalcemia, hepatic encephalopathy, homocystinuria, diabetic ketoacidosis). The associated physical examination findings, laboratory findings, and patterns of prevalence and onset reflect those of the etiological medical condition.

General medical conditions
- Before the catatonia specifier is used in neurodevelopmental, psychotic, bipolar, depressive, or other mental disorders, a wide variety of other medical conditions need to be ruled out; these conditions include, but are not limited to, medical conditions due to infectious, metabolic, or neurological conditions. Catatonia can also be caused by paraneoplastic and limbic encephalitidies (such as anti-NMDA receptor antibody encephalitis), ictal and post-ictal states, posterior reversible encephalopathy syndrome, and lupus. If all other medical or psychiatric causes are ruled out, catatonia can occur as an isolated syndrome without an obvious underlying cause (idiopathic catatonia).
Substance-induced catatonia
- Substances associated with catatonia include dopamine antagonists, tacrolimus, disulfiram, and phencyclidine.
Medication-related side effect
- Catatonia can also be a side effect of a medication. Because of the seriousness of the complications, particular attention should be paid to the possibility that the catatonia is attributable to neuroleptic malignant syndrome.
Extrapyramidal parkinsonism
- Individuals with parkinsonism will have a distinctive tremor, but it is not negativistic and lacks any unusual catatonic psychomotor symptoms.
Delirium
- A separate diagnosis of catatonic disorder due to another medical condition is not given if the catatonia occurs exclusively during the course of a delirium or neuroleptic malignant syndrome. If the individual is on an antipsychotic medication, consideration should be given to medication-induced movement disorders (e.g. - abnormal positioning may be due to neuroleptic-induced acute dystonia) or neuroleptic malignant syndrome (e.g. - catatonic-like features may be present, along with associated vital sign and/or laboratory abnormalities). Although delirium is explicitly an exclusionary criterion in the DSM-5 criterion, there remains some controversy about the overlap and relationship between delirium and catatonia.^[10]^[11] Some clinicians believe that catatonia may overlap or coexist with a hypoactive delirium, and may assess for catatonia by looking for decreased eye blink, or resistance to eye and mouth opening.^[12]
Locked-in syndrome
- Locked-in syndrome is caused by pontine lesions, and can be distinguished from catatonia because patients will usually try to communicate with their eyes.
Coma/vegetative state
- Patients in a persistent vegetative state may also appear to be catatonic.
Stiff person syndrome
- Stiff person syndrome is an autoimmune disorder that presents during severe stress with intense lower extremity spasmodic stiffness that may look like catatonic posturing. However, these patients can speak and talk about their pain.
Nonconvulsive status epilepticus
- Nonconvulsive status epilepticus can also mimic a catatonic-like state. Thus electroencephalography is essential for a prompt diagnosis and treatment of the seizure.

Low serum iron is associated with progression to malignant catatonia and NMS
Serum creatine kinase

See also: University of Rochester: Bush-Francis Catatonia Rating Scale Training Manual and Coding Guide

Prior to the physical exam, it is important to check the chart for reports from previous 24 hours; check for oral intake, vital signs, any behaviour changes or incidents. A physical examination based on the Bush-Francis Catatonia Rating Scale can help guide the exam for catatonia:

Physical Exam for Catatonia

Sign	Exam	Pathological Response
Posturing	Observe the patient	Patient takes on postures on without any clear purpose
Grimacing	Observe the patient	Grimacing is posturing of muscles of facial expression
Stereotypy	Observe the patient	Excessive repetition of a normally goal-directed behaviour (like buttoning a shirt 30 times an hour)
Mannerisms	Observe the patient	Mannerisms are more purposeless than stereotypy
Verbigeration	Observe the patient	Repeating a certain word or sentence WITHOUT a stimulus
Perseveration	Talk to the patient	Repeating a word or phrase WITH a stimulus (i.e. - repeating something a clinician has said)
Mutism	Observe the patient while trying to engage in conversation	Mute
Grasp reflex	Firmly place two fingers in patient's palm	Tightly grasps your fingers (± even if asked not to)
Opposition (Gegenhalten)	Instruct patient to “keep your arm loose”, move patient's arm horizontally back and forth by the wrist, with varying degrees of lighter and heavier force	Automatically resists movement in each direction, matching your strength with each move (i.e. - the more you push the stronger resistance you get)
Negativism	Ask patient to look at you	Turns away
Echopraxia	Scratch your head or nose in an exaggerated way	Copies (±even if asked not to)
Waxy flexibility	Reposition patient's arm into an unusual (but painless) position	Initial resistance, then allows self to be repositioned and holds the pose (e.g. > 1 minute)
Anglepoise (Mitgehen)	Say, “Don’t let me raise your arm,” then push patient's arm in different directions with just your finger	You can move patient's arm with the lightest touch (“like an anglepoise lamp”)
Automatic obedience	• Reach into your pocket and say: “Stick out your tongue, I need to stick a pin in it”. • Extend your hand, saying, “Please don’t shake my hand	• Sticks tongue out (Don’t actually poke with a pin!) • Shakes your hand (± won’t let go)
Ambitendence	• Extend your hand, saying, “Please don’t shake my hand” • Instruct: “Please walk to the end of the room and back	• Oscillates (e.g. - reaching out then retracting hand repeatedly) • Takes a step away, then back, then away again

German 101

Gegenhalten (from German: to resist or hold against) is a form of hypertonia characterized by involuntary variable resistance during a passive movement (i.e. - a movement without effort). It can be elicited moving a patient’s forearm rapidly from a contracted to a stretched position, after instructing the patient not to resist. It is a primitive reflex, absent in adults, but can occur in association with frontal lobe disorders, generalized degenerative diseases, and catatonia. It is different from cogwheel rigidity, a sign of extrapyramidal syymptoms.
Mitgehen (from German: to take part in)is an extreme form of mitmachen in which very slight pressure leads to movement in any direction, also called the “anglepoise” effect or “anglepoise lamp sign”.
- In mitmachen, one's body can be put into any posture, despite instructions given to resist.

Research on the treatment of catatonia is scarce, but there is overwhelming clinical evidence of the efficacy of benzodiazepines and electroconvulsive therapy.^[13] Unfortunately, studies on the treatment of catatonia remains limited to mostly open-label studies or case reports.^[14]^[15]

Recommendations for treatment of catatonia

1st line	ECT, lorazepam IV, q6-8 hours x 2-3 days (zolpidem could be considered)^[16]
2nd line	Memantine 10mg PO daily, titrate over 3-4 days to 20mg daily Amantadine 100mg PO daily, titrated over 3-4 days to 600mg (in divided doses) (Prescribe the above as monotherapy or in combination with a benzodiazepine)
3rd line	Valproic acid 500-1500mg PO daily Carbamazepine 300-600mg PO daily (May be useful if the catatonia is related to underlying mania)
Last line	Aripiprazole 10-30mg PO daily Olanzapine 2.5-10mg PO daily Clozapine 200-300mg PO Daily There is the potential to worsen catatonia or cause conversion to a malignant catatonia.

A lorazepam 2mg intravenous (IV) challenge can be a helpful diagnostic test for catatonia. While a negative response does not rule out catatonia, many patients will show improvement with even a single dose.^[17]
Patients with catatonia usually respond within 30 minutes (range 3 to 24 hours).
Around 70% of patients with catatonia will respond to lorazepam.
- One study suggested that up to 85% of patients will have complete resolution of catatonic features within 3 hours of receiving 1 to 3 mg of IM or sublingual lorazepam.^[18]
After the challenge, a standing dose of lorazepam 2 mg q4-6 hours is a usual treatment.
- Some patients might even require titration up to 30 mg daily, especially in cases with malignant symptoms.
- Doses should only be held if there is concern about respiratory depression due to over-sedation, and not for sedation alone.
- This is because regular dosing with lorazepam is important to fully remit the symptoms of catatonia.
IV lorazepam is preferred over other routes such as (PO) or others benzodiazepines due to its quick onset, preference for the GABA-A receptor, and longer duration of effect.
- IM administration can also be considered if IV is not available.

Electroconvulsive Therapy (ECT) is the definitive treatment for cases where catatonia persists for more than 2 to 3 days or if there are malignant features.
ECT works synergistically with benzodiazepines, typical response rates reach 80%. Bitemporal (PT) ECT is recommended, 3 times per week for at least a total of 6 sessions.
ECT is thought to treat catatonia by increasing cerebral blood flow to the orbitofrontal and parietal cortex, increasing GABA activity and GABA receptor expression.
The increased release of dopamine and modulation of dopamine receptors is another mechanism thought to improve symptoms.

Mood stabilizers may be useful if the catatonia is related to underlying mania.

Antipsychotics are a last line treatment because of their potential to worsen catatonia or cause conversion to a malignant catatonia. Aripiprazole may have the lowest risk due to its partial-agonist activity. Antipsychotics should always be given with a benzodiazepine, and low-potency atypicals are recommended. If the catatonia occurs in the setting of clozapine withdrawal, re-initiation of clozapine should be a first-line strategy.

In addition to treatment of the catatonic symptoms using the above treatments, the full resolution of symptoms often requires treatment of the underlying etiology of the catatonia. This can be challenging in cases of psychosis, which may require a careful balance of antipsychotics and benzodiazepines.

Thromboprophylaxis for DVT risk (due to immobility), swallowing assessments, and physiotherapy for mobility/contractures is important for part of supportive care.