Memantine Treatment of Aggressive Behavior

David L. Ginsberg, MD

Director of Outpatient Services, Tisch Hospital’s Department of Psychiatry, New York University Medical Center

The NMDA receptor may be involved in the pathophysiology of several neuropsychiatric diseases, including schizophrenia, mood disorders, obsessive-compulsive disorder, and autism (Goff et al. 2001; Carlsson 1998). Memantine is an N-methyl-D-aspartic acid (NMDA) receptor antagonist approved for moderate to severe Alzheimer’s disease. Now comes a report of an adult with autistic disorder whose disruptive behavior in the workplace improved during a trial of memantine (Erickson et al. 2006).

A 23 year-old man was diagnosed with autistic disorder at age 2. He was initially referred for evaluation in 2004 following the loss of 2 jobs due to reported harassing and intrusive behavior. Intense interest in coworkers had led to physically intimidating behavior and angry responses to supervisory intervention. This aggressive behavior was the result, at least in part, of the patient’s difficulty in understanding what was being asked of him and of his impaired social skills and language. As a young child, the patient had undergone a brief trial of psychostimulants but otherwise had no prior courses of psychotropic medications. Neuropsychological testing revealed his cognitive abilities to be in the low-normal range. The patient’s medical history was significant for ulcerative colitis, for which he was prescribed stable doses of mesalamine, azathioprine, and folic acid. His last flare-up of ulcerative colitis had occurred approximately 8 months previously.

After a disruptive argument with supervisors on a new job, the patient was prescribed memantine 5 mg at bedtime for 2 weeks, which was subsequently increased to 5 mg twice daily. At a follow-up visit the patient complained that his morning dose was making him tired so the morning dose was changed to 10 mg at bedtime. Moreover, he reported that he felt calm at work, and that he had had no further work-related conflicts. His improved demeanor and behavior were corroborated by his job coach and by his parents. In addition, the patient also demonstrated decreased impulsivity and social withdrawal. These improvements were sustained at his last follow-up visit after 8 months of memantine treatment.

While this appears to be the first published report on the use of memantine for aggressive behavior in pervasive developmental disorders, the drug has been used successfully in children and adolescents with this condition for improving motor planning, attention, language, and repetitive behaviors (Chez et al. 2004). Furthermore, based on a single-blind, placebo-controlled pilot study in autistic children and young adults, D-Cycloserine, a partial agonist at the glycine site of the NMDA glutamate receptor, has shown efficacy for social withdrawal (Posey et al. 2004). Given recent reports associating adverse reactions such as psychosis (Huey et al. 2005) and seizures (Peltz et al. 2005) with memantine, additional controlled studies are indicated to confirm these preliminary findings.

References

Goff DC , Coyle JT. The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry 2001; 158:1367-1377.

Carlsson ML. Hypothesis: is infantile autism a hypoglutamatergic disorder? Relevance of glutamate-serotonin interactions for pharmacotherapy. J Neural Transm 1998; 105:525-535.

Erickson CA, Chambers JE. Memantine for disruptive behavior in autistic disorder (letter). J Clin Psychiatry 2006; 67:1000.

Chez MG, Hung PC, Chin K, et al. Memantine experience in children and adolescents with autism spectrum disorders (abstract). Ann Neurol 2004; 56:C-10.

Posey DJ, Kem DL, Swiezy NB, et al. A pilot study of D-cycloserine in autistic disorder. Am J Psychiatry 2004; 161:2115-2117.

Huey ED, Dustin IH, Overman GP, et al. Development of subtle psychotic symptoms with Memantine: a case report. J Clin Psychiatry 2005; 66:658-659.

Peltz G, Pacific DM, Joviasky JA, et al. Seizures associated with memantine use. Am J Health Syst Pharm 2005; 62:420-421.