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Catatonia: recognition, management, and prevention of complications.

Mr. W, age 50, who has been diagnosed with hypertension and catatonia associated with schizophrenia, is brought to the emergency department by his case manager for evaluation of increasing disorganization, inability to function, and nonadherence to medications. He has not been bathing, eating, or drinking. During the admission interview, he is mute, and is noted to have purposeless activity, alternating between rocking from leg to leg to pacing in circles. At times Mr. W holds a rigid, prayer-type posture with his arms. Negativism is present, primarily opposition to interviewer requests.

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)

* carbidopa/levodopa

* methylphenidate

* 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.

CASE CONTINUED

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.

Disclosures

The authors report no financial relationships with any company whose products are mentioned in this article, or with manufacturers of competing products.

Practice Points

* 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)

Related Resources

* 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

Clinical Point

Benzodiazepines are a first-line option for the management of catatonia

Clinical Point

If high doses of benzodiazepines are not effective within 48 to 72 hours, ECT should be considered

Clinical Point

Antipsychotics carry a risk of potentially worsening catatonia

Clinical Point

Consider ECT initially in life-threatening cases and for patients with malignant catatonia

References

(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.
Publication:Current Psychiatry
Date:Dec 1, 2018
Words:2573
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