Continuing Education Activity

Catatonic schizophrenia is one of the classical clinical subtypes of schizophrenia. The concept of catatonic symptoms in schizophrenia has changed throughout the years, with relevant implications in the treatment approach and prognosis. This activity reviews the evaluation and management of catatonic schizophrenia and highlights the role of the healthcare team in the care of patients with this condition.

Objectives:

• Identify the pathophysiology of catatonic schizophrenia.
• Review the physical exam findings associated with catatonic schizophrenia.
• Summarize management considerations for patients with catatonic schizophrenia and compare with treatment for catatonia secondary to mood or neurological disorders.
• Outline the importance of improving care coordination amongst the interprofessional team to improve outcomes for patients with catatonic schizophrenia.

Introduction

Schizophrenia was divided into five subtypes, including disorganized schizophrenia, paranoid schizophrenia, residual schizophrenia, undifferentiated schizophrenia, and catatonic schizophrenia per the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). In 2013 the American Psychiatric Association (APA) combined all the subtypes under the general category of schizophrenia. "Catatonia" is a word that has undergone multiple definitions and loosely is associated with multiple psychomotor abnormalities and behavioral dysregulation.[1] 

Features of catatonia had been described since the 1800s by prominent physicians such as Kahlbaum and even Kraepelin, who defined catatonia within the larger definition of dementia praecox.[2] There exist many suggested theories elucidating the etiology of catatonia. Kahlbaum has ultimately been credited with the understanding that symptoms such as stupor and catalepsy were part of a larger syndrome of psychomotor abnormalities, which he termed as "catatonia." This can be a part of a larger schizophrenic illness or even a bipolar affective illness or medical illness.[3][4]

The advent of DSM-V has placed catatonia in its own category with schizophrenia as a specifier. Further, there are three types of catatonia that have been classified, including akinetic, hyperkinetic, and malignant catatonia.[5]

Etiology

The etiology of catatonia is multifactorial. One theory is that GABAergic (gamma-aminobutyric acid) neurotransmitters, which regulate both emotional and cognitive functions, become disrupted, leading to catatonic symptoms.[6] This theory postulates that severe negative emotions can cause "tonic immobility," leading to a lack of inhibition at the orbitofrontal cortex (OFC) and hence dysregulation between the ventromedial prefrontal cortex (VMPFC) and the dorsolateral prefrontal cortex (DLPFC), which can cause catatonic symptoms. The DLPFC helps with the cognitive understanding of negative emotions.

Epidemiology

The epidemiology of catatonic schizophrenia can be multivariate. It is said that about 10% of patients in psychiatric inpatient services have catatonic features.[7] On the one hand, the older school of psychiatry associated schizophrenia with catatonia, while newer epidemiological studies show that 20% of patients with catatonia have schizophrenia, and about 45% have symptoms of mood disorders and medical illness.[8] 

One prospective study showed that 7.6% of persons diagnosed with schizophrenia have catatonia.[9] Other studies show that 10%-25% of patients with schizophrenia in the inpatient services can be classified into catatonic schizophrenia, especially when screening tools are used. This can be present at any point-first presentation schizophrenia in someone with lifelong schizophrenia with multiple prior episodes.[10]

Pathophysiology

Dopamine has been cited as a cause of immobility and stupor, and the initial studies researched the role of dopamine in catatonia. However, these studies have been found to be inconclusive.[11]

The N-methyl D-aspartate (NMDA) receptor has been studied extensively both clinically and in mice studies. NMDA encephalitis can produce catatonia-like symptoms.[12] Given that, there have been reports of the use of anti-NMDA agents like amantadine in the treatment of catatonia.[13] The neurotransmitter that is most associated with catatonia is GABA (gamma-amino-butyric acid), and it has been studied extensively. There is decreased GABAergic activity that has been detected in the left sensorimotor cortex via positron emission tomography (PET) imaging.[14] More importantly, GABAergic drugs are the most effective in treating catatonia.[13]

History and Physical

Catatonia again is a complex combination of psychomotor abnormalities and mood and thought processes. There are at least forty different signs and symptoms that have been associated with catatonia. The Diagnostic and Statistical Manual V has criteria for catatonia with specifiers, including that for schizophrenia. Three of the twelve symptoms must be present.[15]

1. Catalepsy (i.e., passive induction of posture held against gravity)
2. Waxy flexibility (i.e., slight and even resistance to positioning)
3. Stupor (no psychomotor activity; not actively relating to the environment)
4. Agitation, not influenced by external stimuli
5. Mutism (i.e., no or little, verbal response but this is not applicable if there is established aphasia)
6. Negativism (i.e., opposing or not responding to external stimuli)
7. Posturing (i.e., spontaneous and active maintenance of a posture against gravity)
8. Mannerisms (i.e., odd caricature of normal actions)
9. Stereotypies (i.e., repetitive, abnormally frequent, non-goal-directed movements)
10. Grimacing
11. Echolalia (i.e., mimicking another's speech)
12. Echopraxia (i.e., mimicking another's movements)

Walter's paper categorizes the symptoms into four major categories: 1. Motor signs (such as immobility) 2. Behavioral signs (negativism) 3. Autonomic instability (tachycardia, hyperthermia) 4. Inability to suppress motor functions (stereotypy, echolalia, echopraxia).[16]

A complete psychiatric history, along with collateral information and a complete neurological examination is key to diagnosing catatonia in a person with schizophrenia. The onset and duration of symptom onset are key to understanding catatonia.

Evaluation

There is now more importance placed now on neuroimaging in cases of catatonia as there has been a noted decrease in functioning in the motor regions of the parietal and frontal cortexes of the cerebrum. Blood chemistries, blood count, serum iron, and even lumbar puncture for autoimmune antibodies for more severe cases of catatonia may be indicated.

The best way to evaluate for symptoms of catatonia is via the Bush Francis Catatonia Rating Scale (BCFRS).[17] This is a 23 item scale, the first 14 are screening items, and two of these 14 need to be present for a positive diagnosis. The severity and description and schema are detailed.[18] The first 14 items described as screeners include excitement, immobility/stupor, staring, posturing, grimacing, stereotypy, echopraxia/echolalia, withdrawal, mannerisms, verbigeration, rigidity, negativism, and waxy flexibility. Additional items that can be evaluated are impulsivity, automatic obedience, mitgehen, gegenhalten, ambitendency, grasp reflex, perseveration, combativeness, and autonomic abnormality.

A benzodiazepine challenge is warranted to reveal a positive diagnosis. Often 2 mg of lorazepam is given PO or IV to a patient, and remission of symptoms can be seen in 10 minutes. Studies have shown at least a 60% change in symptom presentation.[13]

Treatment / Management

The initial management includes supportive measures such as IV fluids and even nasogastric tubes given that patients with catatonia are susceptible to malnutrition, dehydration, pneumonia, etc. The key is early identification of catatonia in a patient with schizophrenia and initiation of treatment.[13]

If a patient is on anti-psychotic medication, this should be stopped immediately, as this may contribute to catatonia in schizophrenia.

The treatment of catatonia in schizophrenia is with benzodiazepines as the first line of treatment and then electroconvulsive therapy (ECT). The Bush-Francis group has conducted a study where they have shown a reduction in the BCFRS by 60% by administrating 2 mg of lorazepam in 10 minutes.[17][18] Multiple case reports, studies, and clinical evidence now points towards the use of benzodiazepines as the standard of treatment of catatonia.[13][19]

In a study of 107 people, it has been seen that two-thirds of patients studied responded adequately to the use of lorazepam. Only one-third were in remission.[20] A large proportion of these were patients with a chronic psychotic disorder (49%), and they were trialed between 3 to 6 mg/day IV of lorazepam. The theory that benzodiazepines are partially effective in catatonic schizophrenia has been replicated on multiple clinical trials by other groups with a larger sample size as well.[19][21] Most studies advocate for doses of lorazepam between 8 to 24 mg/day without causing oversedation. [22] Patients with catatonia can take between 3 to 7 days to respond.

ECT is to be used for patients that have failed an adequate trial of benzodiazepines. ECT is also used for rapid and malignant catatonia with autonomic dysfunction. Specifically, in catatonic schizophrenia, ECT is the treatment of choice. There have been large-scale trials conducted for patients with schizophrenia with intractable catatonia.[23] Results have shown ECT to be effective in about 100% of persons with schizophrenia; however, there is relapse within one year. The largest reviews for catatonic schizophrenia and treatment via ECT have been the chart review study conducted in Iowa.[24] Results of the study show about 53% of persons with catatonic schizophrenia respond to ECT.

Other agents such as zolpidem have been studied for schizophrenia but not for catatonic schizophrenia. However, anti-NMDA agents like amantadine and memantine have been studied in single cases of catatonic schizophrenia and have shown some efficacy.[25]

Lithium has also been studied but has not been studied exclusively for catatonic schizophrenia. Rather its efficacy is seen in cases of recurrent catatonia mostly associated with mood disorders.[26]

Differential Diagnosis

• Neuroleptic malignant syndrome
• Serotonin syndrome
• Malignant hyperthermia
• Akinetic mutism
• Epilepsy (nonconvulsive status epilepticus)
• Locked-in syndrome
• Stiff-person syndrome
• Parkinson disease
• Stroke
• Delirium
• Dementia
• Elective mutism
• Encephalitis

Prognosis

The prognosis of catatonia is favorable if detected early and treated. It is more favorable if catatonia is associated with mood or anxiety disorders. Catatonic schizophrenia carries a poorer prognosis. Most clinical studies that have focused on the use of lorazepam in the treatment of catatonic schizophrenia show poor results.[19]

Another acclaimed study also studied the effects of lorazepam on patients with catatonic schizophrenia and catatonia secondary to other disorders, and importantly patients with catatonic schizophrenia showed only partial remission while the others showed full remission.[27]

The use of ECT is encouraged in catatonia that does not respond to benzodiazepines. However, studies continue to show that catatonic schizophrenia also responds more poorly to ECT compared to catatonia secondary to mood disorders.[28] Several theories propose that catatonic schizophrenia is "phenomenologically different" and hence does not respond as well to the use of benzodiazepines or ECT.[29]

The group lead by Gabor S.Ungvari discusses the psychomotor symptoms that are seen in chronic schizophrenia and underdiagnosis and recognition of the same. Chronic patients may display more stereotypes, automatic mannerisms, and bizarre postures.[29] This carries a worse prognosis in chronic schizophrenia.[30] Gabor S.Ungvari's group has studied catatonic schizophrenia in the four main domains of motor symptoms, including negative/withdrawn phenomena, automatic phenomena, repetitive phenomena, and agitated phenomena. There are associations between sex, younger age, parkinsonism, and negative symptoms of schizophrenia with catatonia.[10][30] 

This group focuses on the presence of psychomotor symptoms in both acute and chronic schizophrenia and the recognition of catatonia within this phenomenon.

Complications

Given that acute catatonia can have its origin with medical or neurological illnesses, initial monitoring with vitals signs notation and treatment with intravenous fluids and nasogastric tubes are warranted. Complications can include aspiration pneumonia, dehydration, embolisms, pressure ulcers, and malnutrition. This can be life-threatening.[31]

Deterrence and Patient Education

The most important aspect includes early detection and treatment. When schizophrenia is traditionally discussed, the focus is usually on the positive symptoms of schizophrenia and less on the negative symptoms. Catatonic schizophrenia is a small percentage of the larger spectrum of a chronic psychotic disorder. However, given its poor prognosis, patients and families would benefit from understanding the nature of symptoms such as stereotypy, automated mannerisms, and immobility to better identify its manifestations.

Pearls and Other Issues

• Catatonia was traditionally associated with schizophrenia. In the latest version of the DSM V (Diagnostic and Statistical Manual V), it has its own category.
• When prominent negative symptoms and psychomotor symptoms are noted in a patient with schizophrenia, consider catatonic schizophrenia.
• Catatonic schizophrenia can be a medical emergency; the BFCRS must be used for early detection. Medical support is often warranted and necessary. Underlying medical and neurological causes must be ruled out.
• Treat medical complications first.
• A benzodiazepine challenge is warranted. Treat aggressively with IV benzodiazepines for at least 3-7 days. Clinical trials have shown the use of up to 24 mg IV lorazepam.
• Catatonic schizophrenia has a poor response to benzodiazepines and often responds better to ECT.
• These patients have a poor prognosis, and relapse and remission of symptoms are usually seen. Maintenance ECT is considered helpful.

Enhancing Healthcare Team Outcomes

One way of enhancing health care outcomes is by collaborating with both medical and neurological staff as catatonic schizophrenia can present as an emergency with life-threatening medical complications and autonomic instability. It is important to understand that underlying delirium or medical or neurological conditions can precipitate a catatonic state.

An interprofessional team consisting of a psychiatrist, hospitalist, nursing services, nutritional, and peer counselor would be effective in providing round-the-clock care to the patient with catatonic schizophrenia. Often extensive psychoeducation with an emphasis on prognosis is helpful for the family of the patient. The hospital stays are longer than regular, and patients often require months-long treatment in an inpatient service. In the outpatient setting, the benzodiazepine must be tapered off slowly to prevent relapse. It is important for both inpatient and outpatient teams to collaborate on care to prevent relapse of symptoms.