Catatonia: recognition, management, and prevention of complications.
Previously stable on paliperidone palmitate, 234 mg IM monthly, Mr. W has refused his past 3 injections. Past psychotropics include clozapine, 250 mg at bedtime (discontinued because Mr. W was repeatedly nonadherent to blood draws), risperidone long-acting injection, 25 mg every 2 weeks, as well as olanzapine, quetiapine, lurasidone, asenapine, lithium, fluoxetine, citalopram, mirtazapine (doses unknown). Previously, electroconvulsive therapy (ECT) was used to successfully treat his catatonia.
On the inpatient psychiatry unit, Mr. W continues to be mute, staying in bed except to use the bathroom. He refuses all food and fluids. The team initiates subcutaneous enoxaparin for deep vein thrombosis (DVT) prophylaxis and IV fluids for hydration. Mr. W receives a benzodiazepine challenge with lorazepam, 2 mg IM. Within 1 hour of receiving lorazepam, he is walking in the hall, speaking to staff, and eating.Therefore, lorazepam, 2 mg IM, 3 times a day, is continued, but the response is unsustained. Ultimately, ECT is initiated.
Catatonia may be present in 10% to 20% of psychiatric inpatients. (1,2) Both stuporous and hyperexcitable catatonia have been described. Catatonia can be associated with schizophrenia, mood disorders, autism spectrum disorders, delirium, or medical comorbidities, and it can be secondary to benzodiazepine withdrawal or clozapine withdrawal. (1-3) Neuroleptic malignant syndrome (NMS) should be ruled out patients with suspected catatonia because some NMS symptoms are similar to catatonic symptoms. The Woodbury Stages of NMS suggest Stage II drug-induced catatonia is a precursor to NMS. (4) Malignant (lethal) catatonia also closely resembles NMS, and some consider NMS a variant of malignant catatonia or drug-induced catatonia. (2,5) Malignant features include fever, tachycardia, elevated blood pressure, and autonomic instability, which can be life-threatening. (1,2,5) Tools such as the Bush-Francis Catatonia Rating Scale (6) or the Northoff Catatonia Scale are useful in evaluating symptoms of catatonia. (2,6) Table 1 (3-6) (page 47) outlines the symptoms and diagnosis of catatonia.
Medical complications can be fatal
Catatonia is associated with multiple medical complications that can result in death if unrecognized or unmanaged (Table 2, (1,2,7) page 48). Lack of movement increases the risk of thromboembolism, contractures, and pressure ulcers. Additionally, limited food and fluid intake increases the risk of dehydration, electrolyte disturbances, and weight loss. Prophylaxis against these complications include IV fluids, DVT prophylaxis with heparin or low-molecular weight heparin, or initiation of a feeding tube if indicated.
Treatment usually starts with lorazepam
Benzodiazepines are a first-line option for the management of catatonia. (2,5) Controversy exists as to effectiveness of different routes of administration. Generally, IV lorazepam is preferred due to its ease of administration, fast onset, and longer duration of action. (1) Some inpatient psychiatric units are unable to administer IV benzodiazepines; in these scenarios, IM administration is preferred to oral benzodiazepines.
The initial lorazepam challenge dose should be 2 mg. A positive response to the lorazepam challenge often confirms the catatonia diagnosis. (2,7) This challenge should be followed by maintenance doses ranging from 6 to 8 mg/d in divided doses (3 or 4 times a day). Higher doses (up to 24 mg/d) are sometimes used. (2,5,8) A recent case report described catatonia remission using lorazepam, 28 mg/d, after unsuccessful ECT. (9) The lorazepam dose prior to ECT was 8 mg/d. (9) Response is usually seen within 3 to 7 days of an adequate dose. (2,8) Parenteral lorazepam typically is continued for several days before converting to oral lorazepam. (1) Approximately 70% to 80% of patients with catatonia will show improvement in symptoms with lorazepam. (2,7,8)
The optimal duration of benzodiazepine treatment is unclear. (2) In some cases, once remission of the underlying illness is achieved, benzodiazepines are discontinued. (2) However, in other cases, symptoms of catatonia may emerge when lorazepam is tapered, therefore suggesting the need for a longer duration of treatment. (2) Despite this high rate of improvement, many patients ultimately receive ECT due to unsustained response or to prevent future episodes of catatonia.
A recent review of 60 Turkish patients with catatonia found 91.7% (n = 55) received oral lorazepam (up to 15 mg/d) as the first-line therapy. (7) Improvement was seen in 23.7% (n = 13) of patients treated with lorazepam, yet 70% (n = 42) showed either no response or partial response, and ultimately received ECT in combination with lorazepam. (7) The lower improvement rate seen in this review may be secondary to the use of oral lorazepam instead of parenteral, or may highlight the frequency in which patients ultimately go on to receive ECT.
ECT. If high doses of benzodiazepines are not effective within 48 to 72 hours, ECT should be considered. (1,7) ECT should be considered sooner for patients with life-threatening catatonia or those who present with excited features or malignant catatonia. (1,2,7) In patients with catatonia, ECT response rates range from 80% to 100%. (2,7) Unal et al (7) reported a 100% response rate if ECT was used as the first-line treatment (n = 5), and a 92.9% (n = 39) response rate after adding ECT to lorazepam. Lorazepam may interfere with the seizure threshold, but if indicated, this medication can be continued. (2) A minimum of 6 ECT treatments are suggested; however, as many as 20 treatments have been needed. (1) Mr. W required a total of 18 ECT treatments. In some cases, maintenance ECT may be required. (2)
Antipsychotics. Discontinuation of antipsychotics is generally encouraged in patients presenting with catatonia. (2,7,8) Antipsychotics carry a risk of potentially worsening catatonia, conversion to malignant catatonia, or precipitation of NMS; therefore, carefully weigh the risks vs benefits. (1,2) If catatonia is secondary to psychosis, as in Mr. W's case, antipsychotics may be considered once catatonia improves. (2) If an antipsychotic is warranted, consider aripiprazole (because of its D2 partial agonist activity) or low-dose olanzapine. (1,2) If catatonia is secondary to clozapine withdrawal, the initial therapy should be clozapine re-initiation. (1) Although high-potency agents, such as haloperidol and risperidone, typically are not preferred, risperidone was restarted for Mr. W because of his history of response to and tolerability of this medication during a previous catatonic episode.
Other treatments. In a recent review, Beach et al (1) described the use of additional agents, mostly in a small number of positive case reports, for managing catatonia. These included:
* Zolpidem (Zolpidem 10 mg as a challenge test, and doses of [less than or equal to] 40 mg/d)
* the N-methyl-D-aspartic acid antagonists amantadine (100 to 600 mg/d) or memantine (5 to 20 mg/d)
* antiepileptics (eg, carbamazepine, topiramate, and divalproex sodium)
* anticholinergics. (1-2)
Lithium has been used in attempts to prevent recurrent catatonia with limited success. (2) There are also a few reports of using transcranial magnetic stimulation (TMS) to manage catatonia. (1)
Beach et al (1) proposed a treatment algorithm in which IV lorazepam (Step 1) and ECT (Step 2) remain the preferred treatments. Next, for Step 3 consider a glutamate antagonist (amantadine or memantine), followed by an antiepileptic (Step 4), and lastly an atypical antipsychotic (aripiprazole, olanzapine, or clozapine) in combination with lorazepam (Step 5).
When indicated, don't delay ECT
Initial management of catatonia is with a benzodiazepine challenge. Ultimately, the gold-standard treatment of catatonia that does not improve with benzodiazepines is ECT, and ECT should be implemented as soon as it is clear that pharmacotherapy is less than fully effective. Consider ECT initially in life-threatening cases and for patients with malignant catatonia. Although additional agents and TMS have been explored, these should be reserved for patients who fail to respond to, or who are not candidates for, benzodiazepines or ECT.
After 5 ECT treatments, Mr. W says a few words, but he communicates primarily with gestures (primarily waving people away). After 10 to 12 ECT treatments, Mr. W becomes more interactive and conversant, and his nutrition improves; however, he still exhibits symptoms of catatonia and is not at baseline. He undergoes a total of 18 ECT treatments. Antipsychotics were initially discontinued; however, given Mr. W's improvement with ECT and the presence of auditory hallucinations, oral risperidone is restarted and titrated to 2 mg, 2 times a day, and he is transitioned back to paliperidone palmitate before he is discharged. Lorazepam is tapered and discontinued. Mr. W is discharged back to his nursing home and is interactive (laughing and joking with family) and attending to his activities of daily living. Unfortunately, Mr. W did not followup with the recommendation for maintenance ECT, and adherence to paliperidone palmitate injections is unknown. Mr. W presented to our facility again 6 months later with symptoms of catatonia and ultimately transferred to a state hospital.
Ericka L. Crouse, PharmD, BCPP, BCGP, and Joel B. Moran, MD
Dr. Crouse is Associate Professor, College of Pharmacy, Clinical Associate Professor, Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia. Dr. Moran is Director, Emergency Psychiatry, Director, Schizophrenia Team, Inpatient Psychiatry Division, Department of Psychiatry, Virginia Commonwealth University Medical Center, Richmond, Virginia.
The authors report no financial relationships with any company whose products are mentioned in this article, or with manufacturers of competing products.
* Initiate appropriate measures to reduce the risk of medical complications from catatonia, such as deep vein thrombosis and dehydration.
* A parenteral lorazepam challenge is considered first-line therapy for catatonia and is useful in confirming the diagnosis.
* Implement electroconvulsive therapy as soon as it is clear that pharmacotherapy is less than fully effective.
Vicki L. Ellingrod, PharmD, FCCP Department Editor
Savvy Psychopharmacology is produced in partnership with the College of Psychiatric and Neurologic Pharmacists cpnp.org.mhc.cpnp.org (journal)
* Fink M, Taylor MA. Catatonia: A clinician's guide to diagnosis and treatment. New York, NY: Cambridge University Press; 2006.
* Carroll BT, Spiegel DR. Catatonia on the consultation liaison service and other clinical settings. Hauppauge, NY: Nova Science Pub Inc.; 2016.
* Benarous X, Raffin M, Ferrafiat V, et al. Catatonia in children and adolescents: new perspectives. Schizophr Res. 2018;200:56-67.
* Malignant Hyperthermia Association of the United States. What is NMSIS? http://www.mhaus.org/nmsis/about-us/what-is-nmsis/.
Drug Brand Names
Amantadine * Symmetrel
Aripiprazole * Ability
Asenapine * Saphris
"Carbamazepine * Carbatrol," Tegretol
Carbidopa/Levodopa * Sinemet
Citalopram * Celexa
Clozapine * Clozaril
Divalproex Sodium * Depakote
Enoxaparin * Lovenox
Fluoxetine * Prozac
Haloperidol * Haldol
"Lithium * Eskalith, Lithobid"
Lorazepam * Ativan
Lurasidone * Latuda
Memantine * Namenda
"Methylphenidate * Concerta," Ritalin
Mirtazapine * Remeron
Olanzapine * Zyprexa
Paliperidone palmitate * Invega Sustenna
Quetiapine * Seroquel
Risperidone * Risperdal
Risperidone long-acting injection * Risperdal Consta
Topiramate * Topamax
Zolpidem * Ambien
Benzodiazepines are a first-line option for the management of catatonia
If high doses of benzodiazepines are not effective within 48 to 72 hours, ECT should be considered
Antipsychotics carry a risk of potentially worsening catatonia
Consider ECT initially in life-threatening cases and for patients with malignant catatonia
(1.) Beach SR, Gomez-Bernal F, Huffman JC, et al. Alternative treatment strategies for catatonia: a systematic review. Gen Hosp Psychiatry. 2017;48:1-19.
(2.) Sienaert P, Dhossche DM, Vancampfort D, et al. A clinical review of the treatment of catatonia. Front Psychiatry. 2014p: 1-6.
(3.) Diagnostic and statistical manual of mental disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
(4.) Pileggi DJ, Cook AM. Neuroleptic malignant syndrome: focus on treatment and rechallenge. Ann Pharmacother. 2016;50(11):973-981.
(5.) Ohi K, Kuwata A, Shi ma da T, et al. Response to benzodiazepines and clinical course in malignant catatonia associated with schizophrenia: a case report. Medicine (Baltimore). 2017,-96(16):e6566. doi: 10.1097/MD.0000000000006566.
(6.) Bush G, Fink M, Petrides G, et al. Catatonia I. Rating scale and standardized examination. Acta Psychiatr Scand. 1996,-93(2):129-136.
(7.) Unal A, Altindag A, Demir B, et al. The use of lorazepam and electroconvulsive therapy in the treatment of catatonia: treatment characteristics and outcomes in 60 patients. J ECT. 201733(4):290-293.
(8.) Fink M, Taylor MA. Neuroleptic malignant syndrome is malignant catatonia, warranting treatments efficacious for catatonia. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(6):1182-1183.
(9.) van der Markt A, Heller HM, van Exel E. A woman with catatonia, what to do after ECT fails: a case report. J ECT. 2016;32(3):e6-7. doi: 10.1097/YCT.0000000000000290.
Table 1 Diagnosis and symptoms of catatonia Primary diagnostic symptoms DSM-5 diagnosis requires 3 (or more) of the following 12 symptoms Stupor * No psychomotor activity; not actively relating to environment Catalepsy * Passive induction of a posture held against gravity Waxy flexibility Slight, even resistance to positioning by examiner; often will remain in the new 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 Mannerism * Odd, circumstantial caricature of normal actions Stereotypy * Repetitive, abnormally frequent, non-goal-directed movements Agitation Agitation does not appear to be influenced by external stimuli Grimacing * Contortion of facial features Echolalia * Mimicking another's speech Echopraxia * Mimicking another's movements Stuporous catatonia: Other signs, occasionally present but not required for diagnosis Ambitendency * Alternating between cooperation and opposition; appears "stuck" motorically Anorexia Decreased or absent oral intake Automatic obedience * Exaggerated cooperation with examiner's inappropriate requests Gegenhalten * Oppositional paratonia (ie, resistance to examiner's motoric examination with force) equal to that applied by examiner Grasp reflex * A frontal release sign where the patient reflexively grasps examiner's finger when placed in their palm Mitgehen * Extreme form of facilitatory paratonia (ie, exaggerated assistance with examiner's motoric examination, when lightly pressed the patient may continue to raise arm even when examination complete ["anglepoise lamp sign"]) Mitmachen Facilitatory paratonia (ie, exaggerated assistance with examiner's motoric examination; when arm lightly pressed patient's movement is exaggerated, may return arm to normal position when examination complete) Palilalia Repetition of words or phrases with increasing speed but decreasing audibility Purposeless activity Seemingly senseless behavior not intended to achieve intelligible goals Psychological pillow Elevation of one's head while supine as if a pillow was present Rigidity * Generally, of lead-pipe variety, reflective of oppositional negativism Staring * Avoidance of eye contact, a reflection of inability to interact with environment Verbigeration * Perseverative repetition of meaningless words or phrases Withdrawal * Retreat from interpersonal contact or social involvement Excitable catatonia: While any of the signs associated with stuporous catatonia may also be present, these additional signs are suggestive of the excitable catatonia subtype Autonomic Vacillation of any vital sign abnormalities * above or below normal range Combativeness * Hostile behaviors, including spontaneous physical aggression Excitement * Motor unrest, state of agitation and hyperactivity, often hyperkinetic but purposeless in nature Impulsivity * Behaviors that are often spontaneous and/or reactive without prior deliberation Psychosis Presence of hallucinations and/or delusions Sources: References 3,6 * Items screened on the Bush-Francis Catatonia Rating Scale Table 2 Medical complications of catatonia Aspiration Dehydration Nutritional deficiency Electrolyte abnormalities Weight loss Venous thromboembolism (ie, pulmonary emboli or deep vein thromboembolism) Acute renal failure Muscle contractures Pressure ulcers Urinary tract infection Cardiac arrest Death Sources: References (1,2,7)
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|Title Annotation:||Savvy Psychopharmacology|
|Author:||Crouse, Ericka L.; Moran, Joel B.|
|Date:||Dec 1, 2018|
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