Evidence-Based Reviews

Treating persistent catatonia when benzodiazepines fail

Current Psychiatry. 2005 March;4(3):56-64

References

1. Taylor MA, Fink M. Catatonia in psychiatric classification: a home of its own. Am J Psychiatry 2003;160:1233-41.

2. Bush G, Fink M, Petrides G, et al. Catatonia I: Rating scale and standardized examination. Acta Psychiatr Scand 1996;93:129-36.

3. Northoff G. What catatonia can tell us about “top-down” modulation:” a neuropsychiatric hypothesis. Brain Behav Sci 2002;25:555-604.

4. Carroll BT. The universal field hypothesis of catatonia and neuroleptic malignant syndrome. CNS Spectrums 2000;5(7):26-33.

5. Carroll BT. Catatonia is the rosetta stone of psychosis (poster presentation). New York: American Psychiatric Association annual meeting, 2004.

6. Barnes MP, Saunders M, Walls TJ, et al. The syndrome of Karl Ludwig Kahlbaum. J Neurol Neurosurg Psychiatry 1986;49:991-6.

7. Carroll BT, Anfinson TJ, Kennedy JC, et al. Catatonic disorder due to general medical conditions. J Neuropsychiatry Clin Neurosci 1994;6:122-33.

8. Hawkins JM, Archer KJ, Strakowski SM, Keck PE. Somatic treatments of catatonia. Int J Psychiatry Med 1995;25:345-69.

9. Rosebush PI, Hildebrand AM, Furlong BG, Mazurek MF. Catatonic syndrome in a general psychiatric inpatient population: frequency, clinical presentation, and response to lorazepam. J Clin Psychiatry 1990;51:357-62.

10. Dose M. Neuroleptic-induced pseudo-catatonia. Pharmacopsychiatry 2001;34:262-4.

11. Keck PE, Jr, Pope HG, Jr, Cohen BM, et al. Risk factors for neuroleptic malignant syndrome. Arch Gen Psychiatry 1989;46:914-18.

12. White DAC. 17 catatonic patients diagnosed as neuroleptic malignant syndrome. CNS Spectrums 2000;5:58-65.

13. Levy WO, Nunez CY. Use of ziprasidone to treat bipolar-associated catatonia. Bipolar Disord 2004;6:166-7.

14. Hesslinger B, Walden J, Normann C. Acute and long-term treatment of catatonia with risperidone. Pharmacopsychiatry 2001;34:25-6.

15. Kruger S, Braunig P. Intravenous valproic acid in the treatment of severe catatonia. J Neuropsychiatry Clin Neurosci 2001;13:303-4.

16. Kritzinger PR, Jordaan GP. Catatonia: an open prospective series with carbamazepine. Int J Neuropsychopharmacol 2001;4:251-7.

17. 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;62:404-6.

18. Namenda (memantine) Package labeling. Forest Laboratories, 2004.

19. Ungvari GS, Chie HFK, Chow LY, et al. Lorazepam for chronic catatonia: a random, double-blind, placebo-controlled, cross-over study. Psychopharmacol 1999;142:393-8.

20. Mobius HJ. Pharmacologic rationale for memantine in chronic cerebral hypoperfusion, especially vascular dementia. Alz Dis Assoc Disord 1999;13(suppl 3):172-8.

CASE CONTINUED: PERSISTENT SYMPTOMS

After three 1-mg doses of lorazepam, Mr. C became more alert and oriented but his catatonia symptoms persisted, as indicated by a Bush-Francis score of 23, significant grasp reflex, and gegenhalten (automatic rather than willful resistance to passive limb movement in proportion to the strength of the stimulus). An attempt to gradually increase lorazepam to 2 mg tid produced delirium. He remained confused even when lorazepam was reduced to 0.5 mg tid, so the drug was discontinued.

Mr. C’s neurologist added amantadine, 100 mg tid, and carbidopa/levodopa, 10/100 mg tid, to treat his parkinsonian rigidity.

WHAT NEXT? OTHER OPTIONS

Antipsychotics have been investigated as a possible treatment for catatonia. The literature suggests that conventional antipsychotics may cause catatonia and atypical antipsychotics may improve it. Conventional antipsychotics are best avoided in catatonia because they:

appear less effective than other treatments in resolving catatonic symptoms^8,10
are associated with catatonic-like side effects, such as rigidity, akinesia, and staring¹⁰
appear to increase NMS risk in patients with catatonic symptoms.^11,12

Atypicals appear more effective in treating catatonia and less likely to cause NMS. Case reports^13,14 indicate many of these agents can be effective and well tolerated in treating catatonic symptoms, although this was not the case for Mr. C.

Anticonvulsants such as valproate¹⁵ and carbamazepine, 600 to 1200 mg/d,¹⁶ may take longer to work than lorazepam but may be options for patients who do not respond to benzodiazepines.^8,9

Amantadine, an N-methyl-D-aspartate (NMDA) antagonist, has been used with some success for catatonia that does not unrespond to lorazepam.¹⁷ However, amantidine’s dopamine agonist activity could worsen underlying psychosis.

Memantine—another NMDA antagonist—differs from amantadine despite having a similar chemical structure. Memantine is a noncompetitive antagonist at the NMDA receptor, without affinity for dopamine, norepinephrine, serotonin, or muscarinic receptors.¹⁸

Although no published data support using memantine in patients with catatonia, it might be considered for those who are not candidates for lorazepam or ECT. For instance, a double-blind, placebo-controlled study found that lorazepam was not effective for catatonic schizophrenia.¹⁹ We have found memantine to help in some patients with catatonic schizophrenia.

CASE CONTINUED: TRIAL OF MEMANTINE

Mr. C remained in a catatonic stupor, but we decided against ECT because he resumed eating and drinking and was not medically at risk. Quetiapine, 100 to 300 mg/d, was tried to address his dementia symptoms, confusion, and poor mentation. This trial was discontinued after Mr. C fell and was readmitted to the medical unit. We then added memantine, 5 mg bid.

In the first week after beginning memantine, Mr. C’s MMSE score was 21, consistent with vascular dementia, but he remained immobile and staring. Motor signs also persisted, including automatic obedience, ambitendency, and a grasp reflex.

The next week, we increased memantine to 10 mg bid. Mr. C was oriented to person, place, and time, and his affect was blunted. His MMSE score increased to 25, showing improved cognition and memory. His Bush-Francis scale score was 6, showing reduced catatonic signs, with remaining mild immobility, bradykinesia, speech-prompt mutism, staring, and grasp reflex.

He maintained this improvement on carbidopa/levodopa, 10/100 tid; amantadine, 100 mg tid; and memantine, 10 mg bid, and was discharged from the nursing home unit.

IMPROVEMENT WITH MEMANTINE

Memantine may reduce excess glutamate at the NMDA receptor in the parietal-SMA-frontal cortical circuit. It may help to increase GABA and dopamine, which are deficient in catatonia. Our patient with vascular dementia had a severe ischemic deficit in the posterior parietal area, as seen on SPECT.

Amantadine, another NMDA receptor antagonist, acts on dopamine neurons and may have anticholinergic-like side effects, whereas memantine does not. Although both drugs share antagonism at the NMDA glutamate receptor, noncompetitive binding is weak for amantadine and moderate for memantine. Memantine has some serotonin (5-HT3) antagonism, but neither agent has direct GABA activity.

Memantine can improve function in vascular dementia.²⁰ Thus, Mr. C’s improvement may have been caused by the drug’s effect on his vascular dementia, the primary neuropsychiatric illness. However, his catatonic signs improved without antipsychotics, cholinesterase inhibitors, benzodiazepines, or ECT. No anticoagulation treatment or cerebral perfusion procedures account for his improved mental status.

CASE CONCLUSION

Mr. C went to live with his son’s family. Although he has problems with calculation, he shows good selfcare. When asked why he did not respond during his catatonic stupor, Mr. C stated that he believed the physician was an Internal Revenue Service agent asking him about serious tax problems. Upon reflection, he said he no longer believes this.

Related resources

Fink M, Taylor MA. Catatonia: a clinician’s guide to diagnosis and treatment. Cambridge, UK: Cambridge University Press, 2003.
Caroff SN, Mann SC, Francis A, Fricchione GE. Catatonia: from psychopathology to neurobiology. Washington, DC: American Psychiatric Publishing, 2004.
Mann SC, Caroff SN, Keck PE Jr, Lazarus A. Neuroleptic malignant syndrome and related conditions (2nd ed). Washington, DC: American Psychiatric Publishing, 2003.
Neuroleptic Malignant Syndrome Information Service. www.NMSIS.org.