LAUSR

Introduction Memantine is a non-competitive N-methyl-d-aspartate receptor antagonist approved for the treatment of moderate to severe Alzheimer's disease(AD). There is a dearth of literature about the emergence of a major neurocognitive disorder in older individuals with developmental delay/mental retardation as well as comorbid inappropriate sexual behavior (ISB). In this population, the development of a major neurocognitive disorder is suspected in the context of new onset cognitive impairment, behavior disturbance and a functional decline. Methods A male with developmental delay who manifested novel, ISB at age 67 which was not controlled by various pharmacologic agents, resolved with the initiation of memantine 10?mg BID. When a recurrence of ISB occurred after 2?years, it resolved when the dose of memantine was increased to 25?mg (administered in two divided doses), which was well tolerated. The patient had been treated in psychiatry for many years for intermittent agitation and anxiety. Results A 67 year-old, single white male with developmental delay, hypertension, diabetes type 2 and hyperlipidemia had long term treatment in psychiatry for intermittent agitation and anxiety. He had been in special education classes through 12th grade. He lived by himself, went to a day program and had caregivers until 5:30pm. There was no history of substance abuse. He was stabilized on paroxetine 50?mg and gabapentin 300?mg TID. Paroxetine was subsequently replaced with citalopram 40?mg to help with symptoms. About a year and a half ago, he developed new onset of ISB towards men who were members of his program, and were mostly under 40. His family stated that the patient had not previously engaged in a homosexual or heterosexual relationship. Incidents of ISB occurred in public bathrooms and other public places. When risperidone 0.25?mg BID was added, this behavior subsided temporarily but resumed. Subsequently, with the gradual increase in gabapentin to 600?mg TID, on 3/28/17 and risperidone to 0.5?mg BID on 3/25/17, in combination with citalopram 40?mg, the undesirable behavior decreased and then subsided. However, as the family was skeptical and keen on starting leuprolide injections, patient was seen by this writer for a second opinion on 4/27/2017. As he was stable, had not had ISB for the past three weeks, I advised against leuprolide. MOCA was 16/30 (with some preservation of executive function as in clock drawing, his short term recall was 3/5 words). Creatinine was 1.28, fasting glucose was 129, vitamin B12 was 291 and B1 was 75. Vitamin B1 and B12 supplements were recommended. Methylmalonate and other labs on 4/29/17 were normal. MRI brain (6/21/17) was unremarkable. The patient was seen again on 6/27/17 due to the family's concern about short term memory impairment (was losing his train of thought, could not figure out how to push his car seat back etc). His gait was unsteady. ISB had ceased about 2 months ago. The family thought that after gabapentin was increased to 600?mg TID, he had become more confused, forgetful and unsteady. The patient was taking risperidone 0.5?mg BID, gabapentin 600?mg TID and citalopram 40?mg daily. MMSE at this visit was 17/30. Memantine was initiated at 5?mg daily to be gradually increased to 10?mg BID. A tapering regimen for gabapentin with 300?mg BID and 600?mg at pm was recommended. On 7/30/17, he became lethargic, had slurred speech and sustained falls. Subsequently, the dose of gabapentin was decreased to 600mg daily and later to 300?mg daily. On 8/22/17, the patient was noted to be doing very well with improved cognition and resolution of ISB. He was taking memantine 10?mg in am 20?mg in the evening. As a higher than recommended dose was being administered mistakenly by care providers, memantine was decreased to 10?mg BID. After two years of stability, a recurrence of ISB was reported. The patient began pursuing a gentleman from his program somewhat obsessively in a sexual manner. When he was examined on 4/9/19, there was no change in his MOCA score (16/30). Recent creatinine was 1.27, fasting blood glucose was 121. Memantine was increased to 10?mg in am and 15?mg at pm to target ISB. On 4/30/19, given its high dose, citalopram 40?mg was replaced with escitalopram 15?mg daily. At follow up visit on 5/21/19, there had not been any ISB after the dose of memantine was increased to 25?mg daily. However, there remained a concern about patient's intermittent belligerence. It was noted that he had been taking a lower dose of risperidone at 0.25?mg twice daily. This was subsequently increased to 0.5?mg twice daily. On 6/12/19, the patient's family reported continued remittance of ISB with the increased dose of memantine as well as resolution of intermittent agitation at the higher dose of risperidone. This patient is stable to date with no further intervention. Conclusions Resolution of ISB in a patient with developmental delay comorbid with major neurocognitive disorder is a previously unreported therapeutic effect of memantine. This patient's ISB was controlled with the addition memantine 20?mg daily after multiple failed trials of various classes of psychotropics. Two years later, the reemergence of ISB was adequately controlled with the increased dose of 25?mg which is a higher than recommended dose of this medication, and was well tolerated. Memantine could be a promising medication for the control of ISB in this challenging population when used as an adjunct. Further studies could be considered to determine whether memantine would be helpful as monotherapy for ISB in major neurocognitive as this measure was not possible in this patient, given that he was already on a medication regimen that had stabilized his other psychiatric manifestations over the years. This research was funded by: NA