CATATONIA

Presented by
Kristine H. Nguyen
Doctor of Pharmacy Candidate
Chapman University School of Pharmacy C/O 2022
 Table of Contents
Chapter 1. Introduction: General Information About Catatonia
◦ Catatonia Definition
◦ Pathophysiology
◦ Differential Diagnosis
◦ Epidemiology
◦ Catatonia Subtypes
◦ Complications of Catatonia
Chapter 2. Treatment Options
◦ Pharmacological Options
◦ Non-Pharmacological Options
Chapter 3. References
CHAPTER 1
Introduction to Catatonia
 What is Catatonia?
A behavioral syndrome marked by immobility commonly associated with various disturbed mental states:
◦ Schizophrenia
◦ Bipolar Disorder with psychotic features (schizoaffective)
◦ Autism Spectrum Disorder
◦ Major Depressive Disorder
Catatonia can be drug-induced as well.

Psychotropic Drugs Non-Psychotropic Drugs

fluphenazine, haloperidol, risperidone, steroids, disulfran, ciprofloxacin, Some
clozapine benzodiazepines, phencyclidine,
cannabis, mescaline, lysergic acid
diethylamide (LSD), cocaine, ecstasy
What is Catatonia?
Other relevant conditions associated with catatonia:
◦ Seizures

(continued)
◦ Brain infections
◦ Intracranial mass lesions
◦ Delirium (Encephalopathy)
Common Signs
and Symptoms of
Catatonia:

◦ Immobility
◦ Rigidity
◦ Mutism
◦ Posturing
◦ Excessive motor activity
◦ Stupor
◦ Negativism
◦ Staring
◦ Echolalia

Source:
https://www.verywellmind.com/what-is-catatonic-schizophrenia-2794979 
 Pathophysiology of Catatonia
Pathophysiology remains unclear. However, there are several hypotheses.

1. Alterations in the pathway that connects the basal ganglia and thalamus
2. Alterations in the prefrontal, orbitofrontal, and parietal cortices
3. Deficits in the visual-spatial abilities that involves the right parietal cortex
function
4. Decreased activity at gamma-butyric acid A (GABA)
5. Decreased activity in dopamine a receptors
6. Increased activity at N-methyl-D-aspartate receptors

https://en.wikipedia.org/wiki/Basal_ganglia
 Epidemiology of Catatonia
Catatonia is more common in patients
◦ Patients over the age of 65
◦ Patients with major depression or bipolar disorder
◦ Patients who are females compared to males
◦ Patients with older aged mothers (35+)*
◦ Patients in the lower socioeconomic class*
◦ Patients with at least one parent diagnosed with schizophrenia*

Source: Kleinhaus et. Al.

* In the context of patients diagnosed with catatonia associated with schizophrenia in comparison to “other” schizophrenia
 Catatonia Subtypes
◦ There are two major catatonia
subgroups: Subtypes Common Symptoms
◦ Nonmalignant subgroup Retarded Mutism, inhibited movement,
◦ Retarded posturing, rigidity, negativism,
staring
◦ Excited
Excited Excessive motor activity,
◦ Malignant subgroup restlessness, impulsivity,
◦ Malignant frenzy, agitation, combativeness
Malignant Fever, autonomic instability,
Why do we care about these delirium, rigidity
subtypes?
DIFFERENTIA
L DIAGNOSIS
The symptoms of catatonia are
not specific to catatonia.
Parkinson’s Disease
Advance Dementia
Serotonin Syndrome
Neuroleptic Malignant Syndrome
 So, Why Do We Care?
◦ Due to the nature of the catatonia symptoms, if left untreated, chronic catatonia can cause
◦ Aspiration Pneumonia
◦ Deep-vein thrombosis (DVT)/ Pulmonary Embolism (PE)
◦ Urinary Retention
◦ Ulcers
◦ Constipation with Impaction
◦ Malnutrition
◦ Death
In addition to these complications, patient’s underlying psychiatric conditions may not be appropriately
treated due to lack of propere response.
 CHAPTER 2
Pharmacological and Non-Pharmacological Options
 Important Considerations
◦ Regardless of catatonia subtype, proper management and preventative treatments should be considered for
◦ Dehydration and malnutrition
◦ DVT and PE
◦ Contractures
◦ Ulcers

In addition to those mentioned above, management for symptoms more specific to malignant catatonia
should be considered
◦ Hyperthermia
◦ Hypertension
◦ Cardiopulmonary instability
Goal of
Treatment
Outline of pharmacological
options:
1. Benzodiazepines
2. Antipsychotics
1. First-generation
antipsychotics
2. Second-generation
antipsychotics
3. Mood stabilizers
4. Other
1. NMDA-Receptor
Antagonists
2. Dopamine Agonists
 Benzodiazepines
◦ Mechanism of Action: Enhances the gamma-aminobutyric acid (GABA)
◦ Benzodiazepines found in practice for catatonia:
◦ Lorazepam
◦ Diazepam
◦ In Huang, 2 out of the 14 schizophrenic patients with catatonia responded to diazepam after having failed to respond to 2 consecutive doses
of lorazepam.
◦ Midazolam
◦ In Raymond et.al., a 65-year-old man with no history of psychiatric illness nor substance abuse or any use of psychotropic drugs diagnosed
with catatonia was treated with Midazolam 1 mg SC.
◦ Clonazepam

Lorazepam is the most common benzodiazepine for both treatment and diagnosis of catatonia. Why?
1. Available in various formulations (IV, IM, PO, Sublingual)
2. Metabolized by glucuronidation (non-CYP450)
3. Most studied benzodiazepine for both treatment and diagnosis
 More on Lorazepam
◦ For diagnosis
◦ Lorazepam IV: 1 to 2 mg once; if no response within 5 to 10 minutes, repeat dose once
◦ Lorazepam IM, Oral (IR), Sublingual: 2 mg once; may administer up to 2 additional doses at 3-hour
intervals as needed

◦ For treatment
◦ Lorazepam IM, IV, Oral (IR): Initial with 1 to 2 mg TID; may increase based on response in
increments of 3 mg every 1 to 2 days (max dose of 30 mg/day)
◦ Maintenance therapy may be continued for 3 to 6 months to prevent refractory cases
 Lorazepam for
Chronic Catatonia?
◦ In Ungvari et. al, the randomized, double-
blind, placebo-controlled cross-over study
tested 18 clinically stable schizophrenic
patients who presented with catatonia’s
response to 6mg/day of Lorazepam for 6
weeks (total duration 12 weeks)
◦ Patients were given either 6 mg/day
lorazepam than placebo or placebo than
6mg/day lorazepam
◦ A 4-week washout period in between (1
Source: Ungvari et. al. week of titrating down followed by 3
weeks of drug-free) ensued
Lorazepam for Assessment Category Scales 
Chronic Psychopathology •Brief Psychiatric Rating Scale
Catatonia? •Hamilton Depression Rating Scale
•Global Assessment Scale
◦ These patients’ •Clinical Global Impression 
psychopathology, drug- •Nurses’ Observation Scale for inpatient
induced motor-symptoms, Evaluation 
and catatonia were
assessed through various
scales. Drug-induced motor symptoms •Abnormal Involuntary Movement Scale
•Simpson-Angus Scale
•Barnes Akathisia Scale 
•Van Putten Akinesia Scale 

Catatonia •Bush-Francois Catatonia Rating Scale 

•Modified Rogers Scale 
 Lorazepam for Chronic Catatonia?

Source. Ungvari et. al.

BPRS (Brief Psychiatric Rating Scale); HRDS (Hamilton Depression Rating Scale); SANS (Scale for the Assessment of Negative Symptoms); GAS
(Global Assessment Scale); NOSIE (Nurses’ Observation Scale for Inpatient Evaluation); MRS (Modified Rogers Scale); SAS (Simpson-Angus Scale);
AIMS (Abnormal Involuntary Movement Scale)
 Antipsychotics
◦ Antipsychotics used for the treatment of catatonia can cause
◦ Possible exacerbation or perseveration of the catatonic state
◦ Possible development of the catatonic state to neuroleptic malignant syndrome
While first-generation antipsychotics are generally not recommended, certain studies on specific second-generation antipsychotics
have shown some efficacy towards managing catatonia:
◦ Olanzapine
◦ In Martenyi et.al., 35 schizophrenic patients with catatonic symptoms that were selected from 7 open-label and double-blind
clinical trials showed that the PANSS (Positive and Negative Syndrome Scale) and the composite score of catatonic signs and
symptoms (posturing, mannerism, excitement, and motor retardation) from a priori defined criteria of catatonic signs and
symptoms (pulled from PANSS) improved. 
◦ Clozapine
◦ Risperidone
◦ In Girish et.al., a double-blind trial of 14 patients with catatonia who was non-responsive to lorazepam were randomly given either bilateral
electroconvulsive therapy and placebo or fake electroconvulsive therapy and risperidone 4-6mg/day. The PANSS and the BFCRS scores were
significantly reduced in the ECT and placebo compared to the fake ECT and risperidone.
◦ Quetiapine
 Mood Stabilizers
◦ Valproic Acid
◦ In Kruger et. al., a case report detailing a 38-year-old-man who was diagnosed with catatonic schizophrenia
at the age of 18 who was given a combination of initial valproic acid followed by lorazepam showed a 90%
symptom reduction. Following this, patient was maintained on Valproate 900mg/day and since then, no
admissions for acute catatonic symptoms for 6 months.
◦ Topiramate
◦ Carbamazepine
◦ Lithium
◦ In Petursson, a case report whereby a patient with long-standing periodic catatonic was treated with lithium
and for 9 years since, the patient had remained asymptomatic. However, due to lithium intoxication, the
lithium treatment had to be discontinued and it was observed that patient’s catatonic symptoms reappeared.
Other Available
Pharmacological Options
◦ Dopamine Agonists
◦ Bromocriptine
◦ Mostly used in combination with other treatments such as
benzodiazepines and ECT in malignant catatonia

◦ NMDA-Receptor Antagonists
◦ Memantine
◦ Amantadine
 Electroconvulsive Therapy
◦ Bitemporal electrode placement with brief pulse current deliverance is preferred
◦ However, there are studies that show unilateral ECT could be efficacious with less side effects

◦ Duration of treatment:
◦ At least 6 ECT treatments are given to catatonic patients regardless of the subtypes; however,
up to 20 treatments may be needed to prevent relapse
◦ Generally, a patient would receive ECT daily for up to 5 days followed by three times weekly until
maintained symptom control

◦ Risks associated with ECT

◦ Nausea
◦ Headache
◦ Fatigue
◦ Confusion
◦ Slight memory loss
◦ Aspiration pneumonia
◦ Fracture
◦ Dental and tongue injuries

Source: https://www.nejm.org/doi/full/10.1056/nejmct075234 
Treatment
Algorithm
◦ Malignant Catatonia
◦ First-line treatment
options
◦ Electroconvulsive
therapy with
concurrent
administration of
benzodiazepine

◦ Non-malignant Catatonia
◦ First-line treatment
options
◦ Benzodiazepine
References
THANK YOU!
QUESTIONS?