Gabapentin and Pregabalin to Treat Aggressivity in Dementia: a Systematic Review and Illustrative Case Report

Aims: The prevalence of dementia is rising as life expectancy increases globally. Behavioural and psychological symptoms of dementia (BPSD), including agitation and aggression, are common, presenting a challenge to clinicians and caregivers.

Methods: Following PRISMA guidelines, we systematically reviewed evidence for gabapentin and pregabalin against BPSD symptoms of agitation or aggression in any dementia, using six databases (Pubmed, CINHL, PsychINFO, HealthStar, Embase, and Web of Science). Complementing this formal systematic review, an illustrative case of a patient with BPSD in mixed Alzheimer's/vascular dementia, who appeared to derive benefits in terms of symptom control and functioning from the introduction of gabapentin titrated up to 3600 mg day alongside other interventions, is presented.

Results: Twenty-four relevant articles were identified in the systematic review. There were no randomized trials. Fifteen papers were original case series/case reports of patients treated with these compounds, encompassing 87 patients given gabapentin and six given pregabalin. In 12 of 15 papers, drug treatment was effective in the majority of cases. The remaining nine papers were solely reviews, of which two were described as systematic but predated PRISMA guidelines. Preliminary low-grade evidence based on case series and case reviews suggests possible benefit of gabapentin and pregabalin in patients with BPSD in Alzheimer's disease. These benefits cannot be confirmed until well-powered randomized controlled trials are undertaken. Evidence in frontotemporal dementia is lacking.

Conclusion: Gabapentin and pregabalin could be considered for BPSD when medications having stronger evidence bases (risperidone, other antipsychotics, carbamazepine and citalopram) have been ineffective or present unacceptable risks of adverse outcomes.