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].

AimsThis review and meta-analysis aim to estimate the cumulative incidence of clozapine induced agranulocytosis and leukopenia the impact of the associated factors such as dose of clozapine, duration of follow-up, gender and race on the cumulative incidence.BackgroundClozapine is the only medication licensed for treatment-resistant schizophrenia. There has been a renewed interest in the role of Clozapine in the treatment of Schizophrenia based on strong evidence that favours its efficacy and safety. Despite the evidence that Clozapine has superior efficacy and has been recommended for treatment-resistant cases by the national guidelines, the drug is underutilised.MethodWe included all studies in which clozapine was used for a psychotic illness. We included studies which provided data on two primary indices; Leucopenia or agranulocytosis and neutropenia; defined according to the cut off used by CPMS for total WBC and neutrophil count. Additionally we included studies reporting another blood dyscrasia or death due to agranulocytosis. Studies were identified by searching AMED, BIOSIS, CINAHL, EMBASE, MEDLINE, PsycINFO, PubMed, and registries of Clinical Trials and their monthly updates, hand searches, gray literature, and conference proceedings from the first available date until 2nd February, 2015. The search was updated on 15th March, 2017. The Protocol was initiated and then registered with PROSPERO International prospective register of systematic reviews University of York, Centre for Reviews and Dissemination.ResultThe cumulative incidence of the agranulocytosis in all studies was 00.32 % (CI 00.1-0.63). The cumulative incidence in all studies for different types of blood dyscrasia were following: leucopenia 00.96 % (CI 0.39-1.70), neutropenia 2.93 % (CI 1.49-4.72), other blood dyscrasias 4.64% (CI 2.34-7.52) and any blood dyscrasia was 2.23 (CI 1.46-3.12).ConclusionThe limitations of this review are mainly due to the nature of evidence from the included studies. We adopted a broad inclusion criteria to include all the available evidence. Number of patients started on Clozapine may be withdrawn from the Clozapine on the earliest signs of blood dyscrasias since the introduction of Clozapine monitoring services. This means that the true incidence of agranulocytosis and neutropenia may be higher and this may be a major bias in finding the true incidence of Clozapine induced neutropenia.

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