Use of Low-Dose Gabapentin for Aggressive Behavior in Vascular and Mixed Vascular/Alzheimer Dementia

The study was a retrospective design of consecutive cases of vascular or mixed vascular/Alzheimer dementia referred to the Department and treated with gabapentin over a 6-month period. (In view of recent concerns of the cerebrovascular side effects of antipsychotic medication in treating BPSD, we decided to use gabapentin in those patients theoretically at greatest risk; that is, those with vascular dementia or mixed dementia.) Seven patients who had been referred to the Department of Old Age Psychiatry Dublin South East were included in the study. All met ICD-10²⁰ criteria for vascular dementia or mixed Alzheimer vascular dementia. Each patient had evidence of vascular risk factors and exhibited severe aggressive behavior creating serious concern for their caregivers.

All patients referred to the Old Age Psychiatry service are screened by the referring doctor for evidence of physical illnesses (e.g., infections, constipation, pain, medication side effects), and the view of the referring and treating doctor was that the aggressive behavior was unrelated to any underlying medical or physical health problem complicating their dementia; four were nursing home residents, and three were living at home with family caregivers. Their ages ranged from 63 to 80 (mean age: 74); there were 6 men, 1 woman. Patients engaged in a range of challenging behaviors, including physical aggression causing soft tissue injury, verbal rage episodes, sexually inappropriate behavior, and aggressive behavior resulting in noncompliance with assistance with ADLs.

The most common antipsychotic medication used to treat behavioral problems in these patients at the time of referral was quetiapine, with 6 of the 7 cases receiving daily doses ranging from 25 mg to 150 mg; 3 patients were on treatment with SSRIs previously for depression (2 on escitalopram, 1 on citalopram), and 1 patient was being treated with both quetiapine and molipaxin 75 mg daily (both for BPSD). No patient was on antiepileptic drug treatment at the time of referral.

All patients (see Table 1) were started on gabapentin at doses of 100 mg twice daily and increased to a total daily dose range from 200 mg daily to 600 mg daily. Antipsychotic medication was discontinued in four patients before treatment with gabapentin (as there was clearly no clinically significant response to it), and it was uneventfully discontinued subsequent to gabapentin treatment in the other three patients. Patients were on gabapentin treatment at the time of review from 3 to 5 months. All patients tolerated gabapentin well, and all patients had a significant response to it, both in terms of clinically significant responses. It was felt in each case that, if the aggressive behavior had continued, patients would have had to be transferred to inpatient care or to alternative specialist long-term care facilities.

A 74-year-old male nursing home resident with a history of vascular dementia was referred by his general practitioner with a several-year history of aggressive behavior, with a recent escalation in assaultive episodes. These episodes of physical aggression appeared to have no obvious precipitant and had resulted in one resident sustaining bruising and soft-tissue injuries. Staff expressed concern that they might not be able to manage the patient in his current setting. On assessment, he had moderate cognitive impairment, with very poor short-term memory and no recall of his behavioral outbursts. Routine investigations were normal, and physical examination revealed no obvious physical cause for his behavior. At the time of his referral, he was on treatment with memantine 20 mg daily, donepezil 10 mg daily, and quetiapine 25 mg daily. After review, he was begun on gabapentin 100 mg bid, which was increased to 200 mg bid after 1 week. Within 2 weeks of starting treatment with gabapentin, there were no further aggressive episodes or sexually-disinhibited behavior, and, as a result of this change, a clinical psychology referral request was deferred and subsequently cancelled. Treatment with quetiapine was gradually discontinued without recurrence of aggressive behavior. The improvement was sustained at review 3 months later. Nursing home staff were satisfied with the intervention and were happy to continue to manage the patient in the nursing home.

A 76-year-old male nursing home resident with a background history of vascular dementia was referred to the Psychiatry of Old Age Service with behavioral difficulties. These included intermittent aggression, agitation, and sexually-inappropriate behavior toward nursing staff and other residents. He had longstanding oppositional and aggressive behavior toward staff assisting him with his personal hygiene, grooming, and dressing.

He had a history of a CVA in 2009, after which he had a carotid endarterectomy. On evaluation, he presented as a thin, elderly gentleman, with an anxious affect. He had severe cognitive impairment, with very poor short-term memory and receptive and expressive aphasia. He had no apparent evidence of delusional thoughts or perceptual abnormalities. His mood was euthymic. Routine investigations were normal, and physical examination revealed no obvious physical cause for his behavior. His medication at the time of assessment included quetiapine 50 mg bid, which he had been on for 8 months, without significant benefit. He had been on citalopram 20 mg for 1 year for treatment of depression. He had also been receiving donepezil 10 mg daily for 1 year. He was begun on gabapentin 100 mg bid, and, within 1 week, his agitation had lessened considerably, and there were no further episodes of aggression or intrusive behavior. Staff were able to attend satisfactorily to his personal hygiene. Gabapentin was well tolerated. The nursing home staff and patient’s family were pleased with the effect of the medication. Follow-up 4 months later revealed that the response to treatment with gabapentin had been maintained. Treatment with quetiapine medication was discontinued gradually and uneventfully.

This patient was an 80-year-old man with a 4-year history of gradually deteriorating memory, referred by his general practitioner, who was concerned about his increasing irritability. He had a history of coronary artery disease, atrial fibrillation, and hypercholesterolemia, and was being treated with warfarin. At clinical review, he had patchy cognitive deficits, with poor short-term memory, nominal dysphasia, and visuospatial impairment. An MRI brain scan revealed deep white-matter ischemic changes. A diagnosis of mixed vascular/Alzheimer dementia was made. He had a history of verbal rage episodes, which were precipitated by relatively minor disagreements with his wife. These episodes resulted in his shouting angrily and making threatening gestures toward his wife. She felt intimidated by him, although he had never been physically aggressive toward her. Full medical review by the Medicine for Older People team had not revealed any obvious physical factors that may have contributed to his rage episodes. An initial trial with memantine had been followed by deterioration in these outbursts, and it was discontinued. He was begun on quetiapine, which was gradually titrated up to 75 mg bid, with only partial control of these episodes. At subsequent review, his wife reported that she could no longer care for him at home if his aggressive behavior could not be managed promptly. Gabapentin was begun at a dose of 100 mg bid and increased after 1 week to 200 mg tid. Within 2 weeks, his wife noted that the rage episodes had diminished significantly. He has remained well on this dose of gabapentin after 3 months, and treatment with quetiapine has been discontinued without further verbal aggression.