Gabapentin and pregabalin to treat aggressivity in dementia: a systematic review and illustrative case report

Abstract

AIMSThe 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. METHODSFollowing 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 À1 alongside other interventions, is presented. RESULTSTwenty-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. CONCLUSIONGabapentin 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.British Journal of Clinical Pharmacology Br J Clin Pharmacol (2019) 85 690-703 690 Gabapentin and pregabalin in dementia treatment Br J Clin Pharmacol (2019) 85 690-703 691 Nomenclature of targets and ligandsKey protein targets and ligands in this article are hyperlinked to corresponding entries in the http://www. guidetopharmacology.org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY [90], and are permanently archived in the Concise Guide to PHARMA-COLOGY 2017/18 [91].

The Hyperactivity–Impulsivity–Irritiability–Disinhibition–Aggression–Agitation Domain in Alzheimer’s Disease: Current Management and Future Directions

“…However, whether the effects of these drugs are helpful for long-term control of HIDA domain symptoms is unclear. The evidence for other pharmacological approaches either does not support their use, as is the case for VPA, or is in its infancy, as is the case for AVP-923 (Fhager et al, 2003; Weiner et al, 2005; Birks, 2006; Howard et al, 2007; Kyomen et al, 2007; Ballard et al, 2009; Ng et al, 2009; Rodda et al, 2009; Sommer et al, 2009; Mowla and Pani, 2010; Lockhart et al, 2011; Gallagher and Herrmann, 2014; Cummings et al, 2015; Suzuki and Gen, 2015; Baillon et al, 2018; Kongpakwattana et al, 2018; Sherman et al, 2018; McShane et al, 2019; Supasitthumrong et al, 2019). Overall, substantial improvement is needed to increase the efficacy and reduce the side effects of pharmacotherapies for HIDA domain symptoms.…”

“…Other antiepileptic drugs are much less well studied, usually having only case reports or small RCTs to support or discourage their use. For instance, gabapentin has a handful of case reports suggesting that it may be effective in treating agitation and aggression in dementia but has no prospective cohorts or RCTs (Supasitthumrong et al, 2019). Lamotrigine similarly has low-quality evidence from a retrospective chart review and open-label clinical trial showing that it may reduce agitation in dementia (Ng et al, 2009; Suzuki and Gen, 2015).…”

Management of Neuropsychiatric Symptoms of Dementia: A Comprehensive Review of the Current Literature

“…In a retrospective design of cases Cooney et al [80] found that low-dose gabapentin could be effective in treatment of aggression in patients with vascular dementia. A recent systematic review by Supasitthumrong et al [81] about evidence of gabapentin and pregabalin in the management of NPS found low-evidence for the use of these medications for that matter. There are case series showing positive results with gabapentin, however there are no randomized controlled trials [71].…”

<p>Pain And The Use Of Gabapentinoids In German Nursing Home Residents - Results From An Analysis Based On Statutory Health Insurance Data</p>

“…Blockade of presynaptic voltage-gated calcium channels containing α2δ1-subunits to reduce excitatory neurotransmitter release has become an increasingly popular pharmacological principle that is employed for a variety of diseases and conditions 1. The gabapentinoids, gabapentin and pregabalin, as the currently clinically available compounds in this class of medications are hence being used or have been trialed for management of for instance anxiety and bipolar disorders, behavioral and psychological symptoms of dementia (BPSD), chronic pruritus, epilepsy, hiccups, hot flashes, refractory cough, restless legs syndrome, spinal muscular atrophy, substance abuse disorders, and tinnitus 2–4. They are particularly popular in pain medicine and are therefore employed for the treatment of fibromyalgia, headaches, osteoarthritis, and post-operative as well as peripheral and central neuropathic pain 2,5,6.…”