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Letter to the Editor   |    
Memantine and Catatonic Schizophrenia
CHRISTOPHER THOMAS, Pharm.D., B.C.P.P.
Am J Psychiatry 2005;162:626-626. doi:10.1176/appi.ajp.162.3.626

To the Editor: The use of typical and atypical antipsychotics has provided marked improvement for many schizophrenic patients. Numerous patients, however, do not achieve full remission of symptoms, often having recurrent episodes. Several adjunctive therapies have been researched targeting the N-methyl-d-aspartic acid (NMDA) receptor (1). To our knowledge, this is the only case showing improvement in a patient with schizophrenia possessing catatonic symptoms in which the use of memantine has shown benefit.

Mr. A, a 56-year-old man with schizophrenia, was admitted after police discovered him wandering the streets responding to auditory hallucinations. His symptoms included mutism, staring, posturing, perseveration, stupor, and stereotypy (retrospectively assessed with the Bush Francis Catatonia Rating Scale, score=16) (2). His hospital course was prolonged because of partial response to olanzapine, haloperidol, ziprasidone, and risperidone. There were several psychotic relapses with polydipsia, staring, mutism, immobility, and somatic delusions. He was transferred several times between the acute care and extended care units.

Memantine, 5 mg/day, was started, ziprasidone was discontinued, and clozapine was initiated. The next day, Mr. A’s symptoms improved greatly. He spoke more freely, and a feeling of his head being warm had subsided, as well as his preoccupation with drenching himself in baptismal fashion. His memantine and clozapine doses were titrated to 10 mg b.i.d. and 300 mg/day, respectively. His clozapine level was measured at 509 ng/ml.

Uncertainty as to the efficacy of memantine promoted its discontinuation 9 days after initiation. Mr. A’s condition subsequently worsened, with a return of staring and soaking himself. Memantine was restarted, and his symptoms again significantly improved. Clozapine and memantine were continued, and his Bush Francis Catatonia Rating Scale score was 3, with automatic obedience.

Memantine is an NMDA receptor antagonist that is approved for use in moderate to severe Alzheimer’s disease. Its potential efficacy in schizophrenia may be due to blockade of hyperglutamatergic excitotoxicity in neurons. It is hypothesized that because of a pathological process in the brain, excess glutamate is produced (3). Excess glutamate causes hyperexcitation of glutamate receptors, allowing calcium channels to stay open for prolonged periods. Excessive calcium influx causes free radical damage to the neuron, eventually progressing to neuronal death.

A case report demonstrated the effectiveness of amantadine, an NMDA receptor antagonist with a structure similar to that of memantine, in a patient with schizoaffective psychosis and a Bush Francis Catatonia Rating Scale score of 31 (4). Based upon the effectiveness shown in this patient, memantine may be a useful adjunctive therapy for schizophrenic patients with catatonic symptoms.

Goff DC, Coyle JT: The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry  2001; 158:1367–1377
[PubMed]
[CrossRef]
 
Bush G, Fink M, Petrides, Dowling F, Francis A: Catatonia, I: rating scale and standardized examination. Acta Psychiatr Scand  1996; 93:129–136
[PubMed]
[CrossRef]
 
Northoff G: What catatonia can tell us about "top-down modulation": a neuropsychiatric hypothesis. Behav Brain Sci  2002; 25:555–604
[PubMed]
 
Northoff G, Lins H, Boker H, Danos P, Bogerts B: Therapeutic efficacy of N-methyl D-aspartate antagonist amantadine in febrile catatonia. J Clin Psychopharmacol  1999; 19:484–486
[PubMed]
[CrossRef]
 
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References

Goff DC, Coyle JT: The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry  2001; 158:1367–1377
[PubMed]
[CrossRef]
 
Bush G, Fink M, Petrides, Dowling F, Francis A: Catatonia, I: rating scale and standardized examination. Acta Psychiatr Scand  1996; 93:129–136
[PubMed]
[CrossRef]
 
Northoff G: What catatonia can tell us about "top-down modulation": a neuropsychiatric hypothesis. Behav Brain Sci  2002; 25:555–604
[PubMed]
 
Northoff G, Lins H, Boker H, Danos P, Bogerts B: Therapeutic efficacy of N-methyl D-aspartate antagonist amantadine in febrile catatonia. J Clin Psychopharmacol  1999; 19:484–486
[PubMed]
[CrossRef]
 
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