Psychosomatics 48:534-536, November-December 2007
doi: 10.1176/appi.psy.48.6.534
© 2007 Academy of Psychosomatic Medicine
Treatment of Catatonia With Olanzapine and Amantadine
Parker W. Babington, B.A., and
David R. Spiegel, M.D.
Received August 14, 2006; revised October 29, 2006; accepted November 1, 2006. From Eastern Virginia Medical School Dept. of Psychiatry and Behavioral Sciences, Norfolk, VA. Send correspondence and reprint requests to David R. Spiegel, M.D., Eastern Virginia Medical School Dept. of Psychiatry and Behavioral Sciences, 825 Fairfax Ave., Norfolk, VA 23507. e-mail: spiegedr{at}evms.edu
© 2007 The Academy of Psychosomatic Medicine
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ABSTRACT
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Catatonia is a disorder characterized by mutism, posturing, echophenomena, and negativism. The preferred treatment for non-malignant catatonia is benzodiazepines, which often produce a reduction in symptoms within 24 hours. Presented here is a case report of a 19-year-old woman appearing in a catatonic state that did not respond to lorazepam. On the basis of emerging evidence that atypical antipsychotics and weak N-Methyl-D-Aspartate (NMDA) receptor-antagonists may effectively treat catatonia, we treated our patient with olanzapine and amantadine, which resulted in a dramatic reduction in her catatonic symptoms.
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INTRODUCTION
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Catatonia, as described by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM–IV), has a limited role as a subtype of schizophrenia.1 However, the scientific literature reveals many cases of catatonia independent of schizophrenia. These cases are seen in a wide spectrum of patients, and there is some debate as to the best method of treatment to resolve the various catatonic symptoms that occur. Some reports estimate that catatonic features are present in 10% of acutely hospitalized psychiatric patients.2 The symptoms of catatonia include mutism, negativism, posturing, stereotypy, echophenomena, and passive obedience.3
The exact pathophysiology of catatonia is not known, but several hypotheses regarding neurotransmitter dysfunction have been proposed. Decreased gamma-aminobutyric acid (GABA) activity has been observed in some patients with catatonia. This finding may explain the positive response that many catatonic patients show to benzodiazepines, which are GABAA agonists.3–5 Agents that block dopamine-2 (D2) receptors, such as typical antipsychotics, can induce catatonia in some patients; however, the scientific literature suggests that atypical antipsychotics may be effective in treating catatonia. These findings suggest that regulation of dopamine may be integral to the treatment of catatonia.6,7 Similarly, NMDA receptor-antagonists, such as ketamine, have been associated with the onset of catatonia. However, amantadine, a weaker NMDA receptor-antagonist, has been reported to improve catatonia. In cases that have not responded to benzodiazepines, atypical antipsychotics, amantadine, and anticonvulsants have all been shown to be effective in treating catatonia.8–11
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Case Report
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"Ms. F" is a 19-year-old African American young woman whom the Consultation–Liaison Service at our teaching hospital was asked to evaluate after she presented with altered mental status and abnormal new behaviors. The chief complaint regarding Ms. F was that during the past 3 weeks she had been sleeping poorly, had lost urinary continence, showed decreased communication, and was not taking care of herself. Because of Ms. F’s lack of communication, all history was provided by her mother. Ms. F is autistic but has recently graduated from high school. She had been able to perform her activities of daily living with minor assistance. There was no significant medical history. She does not use alcohol, tobacco, or illicit drugs. There is a family history of diabetes and hypertension. Her brother is autistic, and her grandmother was diagnosed with schizophrenia.
At presentation to the hospital, Ms. F was not oriented to time, person, or place. She exhibited a blunted affect, with significant speech impairment. All speech was limited to sentences of one or two words. Initial management included a computed tomography (CT) of the head, electroencephalogram (EEG), and battery of lab tests to rule out a nonpsychiatric etiology for her altered mental status.
Ms. F’s CBC, urinalysis, basic metabolic profile, ammonia, vitamin B12, and thyroid function tests were normal. Copper, lead, porphyrin, ceruloplasmin, and drug and alcohol tests were negative. Her aspartate aminotransferase and alanine aminotransferase were elevated, but decreased each day of hospitalization, normalizing by the time of discharge. The CT showed small focal outpouchings of cerebrospinal fluid in the right ventricle, but this was determined to be an old finding and not significant for the current situation. The EEG showed generalized background disorganization, with no signs of seizure activity. The lack of evidence for a medical etiology of Ms. F’s mental status change led us to consider psychiatric causes.
On mental status exam, we found Ms. F supine in bed, wearing a hospital gown. She was awake and oriented to person. She was not oriented to place or time. She was continuously drooling and spitting into a towel on her chest. We felt this to be indicative of stereotypy. Ms. F had paucity of speech, answering questions in one- or two-word sentences. She had a blunted affect and could not describe her mood. She had a poor attention span, and exhibited poor short-term memory. She showed motor perseveration and echophenomena. When her arm was tested for rigidity, she continued this motion after the test ended, and did not stop until her arm was grasped and placed back at her side, indicative of motor perseveration. She answered some questions by counting from 1 to 10 repeatedly until told to stop. We felt this to be consistent with verbigeration, although this could also be interpreted as pallalia. When her arms were raised or moved to positions other than resting on the bed, Ms. F held that position until her arms were taken and placed back onto the bed (i.e., she showed posturing). She showed passive obedience, allowing her arm to be raised after being instructed to resist the movement. She was able to perform rapid alternating movements bilaterally but was unable to follow instructions for finger-to-nose testing. Ms. F was able to walk and stand on her toes, but had a slightly wide-based gait. She scored a 29 on the Bush-Francis Catatonia Rating Scale.
A dose of 2 mg intramuscular (IM) lorazepam was administered, but no reversal of symptoms was noted. Lorazepam was discontinued because of her mother’s complaints that it was too sedating. Ms. F was then placed on 100 mg amantadine orally and 5 mg IM olanzapine. On the following day, we noted dramatic improvement in Ms. F’s catatonic symptoms. She was oriented to person and place, and was able to communicate in longer sentences. Her mutism was significantly reduced. Stereotypy and verbigeration were no longer present. Although still showing motor perseveration, she stopped these movements on her own after a few seconds. When postured, Ms. F slowly brought her arms back to resting position instead of holding them up as she had before. Her mother stated that Ms. F was much improved. She now scored a 5 on the Bush-Francis Catatonia Rating Scale. We recommended that Ms. F be placed in an inpatient psychiatric unit of the hospital for further treatment and recovery. Her mother refused this recommendation, and Ms. F was discharged with a follow-up appointment at a hospital near her home.
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Discussion
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This case represents a clinical picture of catatonia with its etiology including new-onset schizophrenia and as a manifestation of autism. Traditionally, catatonia is treated with benzodiazepines. Benzodiazepines’ stimulation of GABAA receptors is believed to be the reason for their efficacy in the treatment of catatonia.4,5 The recent scientific literature has shown that in addition to benzodiazepines, atypical antipsychotics and weak NMDA receptor-antagonists may be effective in treating catatonia.6–10 Because our patient did not respond to lorazepam, we treated her with olanzapine and amantadine. Evidence indicates that classical antipsychotics may aggravate catatonia; however there are indications that atypical antipsychotics may be efficacious in nonmalignant catatonia.7 Pharmacodynamic properties of olanzapine include D2 blockade, weak GABA-agonism, and serotonin (5HT2) antagonism, which may help explain why it proved to be effective. A stronger GABA-agonist, lorazepam, did not attenuate symptoms in our patient. Thus, the effectiveness of olanzapine in the patient did not appear to be secondary to its GABA-agonism. Northoff reports that altered GABA transmission down-regulates subcortical dopamine transmission.11 Thus, as a 5HT2-antagonist, olanzapine could increase dopaminergic transmission subcortically and improve rigidity associated with catatonia. Also, 5HT2 antagonism results in increased dopaminergic transmission in the prefrontal cortex. Behavioral and affective catatonic symptoms correlate with reduced orbitofrontal activity. Thus, the increased dopaminergic transmission frontally could explain improvement in catatonic symptoms.11 Amantadine is a weak NMDA receptor-antagonist, and it has been shown in several case studies to treat the symptoms of catatonia.12 The results of this case, as well as others in the literature, suggest that when benzodiazepines are ineffective in treating catatonia, atypical antipsychotics and amantadine may be useful alternatives.
Although encouraged by our results, we still recognize uncertainties in our interpretations. It is possible that our patient’s delayed response to therapy could have been secondary to treatment with IM lorazepam; however, Huang13 reports that in 86% of patients given IM lorazepam, response is seen within 2 hours. Also, the response of catatonia to lorazepam typically does not occur until dosing reaches the range of 6 mg–12 mg/day.13 It is also possible that our patient did not respond to lorazepam because intravenous (IV) administration might be more efficacious than IM. However, according to Wermeling et al.,14 both IV and IM lorazepam have a bioavailability of 100%. Although amantadine has been reported to improve symptoms of catatonia within 4 to 6 hours, that was reported via the IV route of administration.14 Unfortunately, we were unable to find out how quickly a response could be expected through oral dosing. Finally, although our patient did have residual symptoms of catatonia at discharge, electroconvulsive therapy has also been reported to be a useful modality in the treatment of catatonia.2 However, our patient refused this modality. On the basis of our case report, we propose that further studies testing the treatment of catatonia with both olanzapine and amantadine or monotherapy with olanzapine are warranted.
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ACKNOWLEDGMENTS
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The Mood Disorders section (295.20) in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, text revision (DSM–IV-TR); Washington, DC, American Psychiatric Association, 2000, was used as a reference throughout the article.
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REFERENCES
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- Taylor MA, Fink M: Catatonia in psychiatric classification: a home of its own. Am J Psychiatry 2003; 160:1233–1241[Abstract/Free Full Text]
- Fink M, Taylor MA: Catatonia: A Clinician’s Guide to Diagnosis and Treatment. Cambridge, UK, Cambridge University Press, 2003
- Rosebush PI, Mazurek MF: A consideration of the mechanisms by which lorazepam might treat catatonia. J Clin Psychiatry 1991; 52:187–188
- Salam SA, Pillai AK, Beresford TP: Lorazepam for psychogenic catatonia. Am J Psychiatry 1987; 144:1082–1083[Abstract/Free Full Text]
- Cook EH, Olson K, Pliskin N: Response of organic catatonia to risperidone. Arch Gen Psychiatry 1996; 53:82–83[Abstract/Free Full Text]
- Van Den Eede F, Van Hecke J, Van Dalfsen A, et al: The use of atypical antipsychotics in the treatment of catatonia. Eur Psychiatry 2005; 20:422–429[CrossRef][Medline]
- Northoff G, Lins H, Boker H, et al: Therapeutic efficacy of N–methyl D-aspartate antagonist amantadine in febrile catatonia. J Clin Psychopharmacol 1999; 19:484–486[CrossRef][Medline]
- Carroll BT, Thomas C, Kameshwari J, et al: Treating persistent catatonia when benzodiazepines fail. Curr Psychiatry Online 2005; vol. 4, no. 3
- Muir KW, Grosset DG, Lees KR: Clinical pharmacology of CNS 1102 in volunteers. Ann N Y Acad Sci 1995; 765:279–289[CrossRef][Medline]
- McDaniel WW, Spiegel DR, Sahota AK: Topiramate effect in catatonia: a case series. J Neuropsychiatry Clin Neurosci 2006; 18:234–238[Abstract/Free Full Text]
- Northoff Georg: Neuroimaging and neurophysiology, in Catatonia: From Psychopathology to Neurobiology. Edited by Caroff SN, Mann SC, Francis A, et al. Washington, DC, American Psychiatric Publishing, 2004, pp 77-91
- Northoff G, Eckert J, Fritze J: Glutamatergic dysfunction in catatonia? successful treatment of three acute akinetic catatonic patients with the NMDA antagonist amantadine. J Neurol Neurosurg Psychiatry 1997; 62:404–406[Abstract/Free Full Text]
- Huang TL: Lorazepam and diazepam rapidly relieve catatonic signs in patients with schizophrenia. Psychiatry Clin Neurosci 2005; 59:52–55[Medline]
- Wermeling DP, Miller JL, Archer SM, et al: Bioavailability and pharmacokinetics of lorazepam after intranasal, intravenous, and intramuscular administration. J Clin Pharmacol 2001; 41:1225–1231[Abstract]
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ABSTRACT
INTRODUCTION
