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Letter to the Editor   |    
Aggression in Dementia With Lamotrigine Treatment
SIVAKUMARAN DEVARAJAN , M.D., M.R.C.PSYCH., F.R.C.P.C.; SERDAR M. DURSUN , M.D., PH.D., F.R.C.P.C.
Am J Psychiatry 2000;157:1178-1178. doi:10.1176/appi.ajp.157.7.1178

Frontal lobe dementia is a presenile condition with an insidious onset; it usually appears with deterioration of personality and behavior. The prominent initial symptoms of frontal lobe dementia are apathy, socially inappropriate behavior, impulsivity, aggression, and disinhibition with relative preservation of memory. It may be difficult to control such symptoms, although a variety of medications have been tried, including β blockers, benzodiazepines, antipsychotics, and mood stabilizers, including lithium and divalproex sodium, at a cost of further deterioration in cognition and other side effects (1, 2). We present a case of frontal lobe dementia with various symptoms in a patient who responded well to lamotrigine but not to other treatments.

Ms. A was a 65-year-old woman with a 12-year history of chronic recurrent episodes of major depression. Before that she had excellent premorbid functioning and worked in accounting. After her husband’s suicide when she was 40 years old, she managed to bring up her two sons alone. Treatment of her depression included a variety of antidepressants, which resulted in some improvement that was not sustained. Her last admission was after a 3-month history of repeatedly asking the same questions, picking her nose until it bled, and being verbally and physically aggressive. The episodes of aggression were characterized by hitting, punching, biting, tearing clothes, grunting, barking, screaming, and grimacing—all of which appeared to come on suddenly and involuntarily and were puzzling to her. She had been treated with fluvoxamine, buspirone, lorazepam, vitamin E, thiamine, loxapine, risperidone, and divalproex sodium with little or no improvement.

On admission, in addition to the ongoing problems just listed, Ms. A appeared extremely aggressive and disinhibited, with moderate deterioration in concentration and cognition. Her medications at admission included 1500 mg/day of divalproex sodium (in therapeutic blood concentrations), 2 mg/day of risperidone, and 2–4 mg/day of lorazepam. Preventive measures for aggressive behaviors were applied. However, she convinced the psychiatric trainees and other members of the staff that she would not harm them. The staff believed her, but when approached within an arm’s length, she hit two psychiatric residents, a psychiatrist, and a neurologist and left some with facial bruises and black eyes. After neurological examinations, brain scans (computerized tomography and single photon emission computed tomography), and neuropsychological testing, Ms. A was diagnosed with frontal lobe dementia.

There is evidence that excitotoxic damage, apoptotic signals in synapse loss, and neuronal death in neurodegenerative processes involve excessive activation of glutamate receptors and glutamatergic hyperactivity (3, 4). Lamotrigine, an anticonvulsant and possible mood stabilizer, inhibits presynaptic glutamate release, in addition to its other actions (5).

Therefore, Ms. A was initially treated with a dose of 12.5 mg/day of lamotrigine, which was gradually increased to 100 mg/day over 4 weeks, according to clinical response. All of her symptoms dramatically improved, and she was back to her pleasant premorbid mood. She was maintained with this dose of lamotrigine over 6 months with no relapse. No dermatologic or other side effects were reported.

Lamotrigine is suggested for cases such as this. In addition, preventive measures and pharmacological interventions should be considered. This observation has the limitations of a case report. Controlled studies are necessary.

Anderson IM, Scott K, Harborne G: Serotonin and depression in frontal lobe dementia (letter). Am J Psychiatry  1995; 152:645
 
Bowden CL: Anticonvulsants in bipolar elderly, in Geriatric Psychopharmacology. Edited by Nelson JC. New York, Marcel Dekker, 1998, pp 285–299
 
Harrison PJ, Eastwood SL: Preferential involvement of excitatory neurons in medial temporal lobe in schizophrenia. Lancet 1998; 352:1669–  1673
 
Mattson MP, Keller JN, Begley JG: Evidence for synaptic apoptosis. Exp Neurol  1998; 153:33–48
 
Messenheimer J: Lamotrigine. Epilepsia 1995; 36(suppl 2):S87–S94
 
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References

Anderson IM, Scott K, Harborne G: Serotonin and depression in frontal lobe dementia (letter). Am J Psychiatry  1995; 152:645
 
Bowden CL: Anticonvulsants in bipolar elderly, in Geriatric Psychopharmacology. Edited by Nelson JC. New York, Marcel Dekker, 1998, pp 285–299
 
Harrison PJ, Eastwood SL: Preferential involvement of excitatory neurons in medial temporal lobe in schizophrenia. Lancet 1998; 352:1669–  1673
 
Mattson MP, Keller JN, Begley JG: Evidence for synaptic apoptosis. Exp Neurol  1998; 153:33–48
 
Messenheimer J: Lamotrigine. Epilepsia 1995; 36(suppl 2):S87–S94
 
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