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Objectives: To examine the association between central nervous system (CNS)-active medication use and the risk of fall-related injury in community-dwelling older adults following dementia onset. Further, to evaluate increased risk at higher doses or with a greater number of CNS-active medication classes., Methods: Participants included community-dwelling older adults aged 65 years and older with a dementia diagnosis participating in the Adult Changes in Thought Study. From automated pharmacy data, a time-varying composite measure of CNS-active medication use was created. Central nervous system-active medication use was classified as current (use within prior 30 days), recent (prior 31-90 days), past (prior 91-365 days), and nonuse (no exposure in prior year). For current users, standardized daily doses (SDDs) were calculated for each CNS-active medication and summed across medications, and the number of CNS-active medication classes used was also measured. The outcome was fall-related injury based on emergency department, inpatient, and outpatient International Classification of Diseases, Ninth Revision (ICD-9) and external cause of injury (E) codes., Results: Among 793 subjects, 303 fall-related injuries occurred over a mean follow-up of 3.7 years (2907 total person-years). Relative to nonuse, fall risk was significantly higher for current use (adjusted hazard ratio [HR] 1.59, 95% confidence internal [CI] 1.19-2.12) but not for past or recent use. Among current users, increased risk was seen across SDD levels: HRs (95% CI): 1.77 (1.19-2.62), 1.79 (1.25-2.56), and 1.35 (0.96-1.92) for less than 1 SDD, 1 to less than 2 SDDs, and 2 or more SDDs, respectively (trend test, p=0.14). A trend was seen for increasing risk with a greater number of CNS-active medication classes; however, this was not statistically significant (trend test, p=0.084)., Conclusions: Current use of CNS-active medications was associated with fall-related injury in community-dwelling older adults followed from time of dementia onset, with increased risk even with use of low doses., (© 2019 Pharmacotherapy Publications, Inc.)

Background: Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in patients with dementia. Both pharmacological and non-pharmacological strategies are commonly used to treat these symptoms, but their comparative safety and efficacy is unknown., Methods: We will conduct a systematic review of the published and unpublished literature to retrieve all articles pertaining to outcomes of safety and efficacy associated with pharmacological and non-pharmacological treatments of BPSD for patients living in the community and institutionalized care settings. Our primary outcome of efficacy is a change in aggression. Our primary outcome of safety will be risk of fracture. These primary outcomes were chosen by stakeholders involved in the care of patients experiencing BPSD. Possible secondary outcomes of efficacy will include a change in agitation, depressive symptoms, and night-time behaviors. Possible secondary outcomes of safety will include the risk of stroke, falls, and mortality. All article screening, data abstraction, and risk of bias appraisal will be completed independently by two reviewers. If the assumption of transitivity is valid and the evidence forms a connected network, Bayesian random-effects pairwise and network meta-analyses (NMAs) will be conducted. Relative treatment rankings will be reported with mean ranks and the surface under the cumulative ranking curve., Discussion: We will identify the safest and most efficacious treatment strategies for patients with BPSD from among our most highly ranked treatments. The results of this study will be used to guide decision-making and improve patient care., Systematic Review Registration: PROSPERO registry number CRD42017050130.

Background: Delirium is a very common and distressing neuropsychiatric syndrome in palliative care. Increasing age, the presence of dementia and advanced cancer are well-known predisposing risk factors for delirium development. Sleep-wake cycle disturbance is frequently seen during delirium and melatonin has a pivotal role in the regulation of circadian rhythms. Current evidence across various settings suggests a potential preventative role for melatonin in patients at risk of delirium, but no studies are currently reported in patients with advanced cancer. The aim of this article is to describe the design of a feasibility study that is being conducted to inform a larger randomized, placebo-controlled, double-blind trial (RCT) to evaluate the role of exogenously administered melatonin in preventing delirium in patients with advanced cancer., Methods/design: Adult patients with a cancer diagnosis who are admitted to the palliative care unit will be randomized into a treatment or placebo group. The pharmacological intervention consists of a single daily dose of immediate-release melatonin (3 mg) at 21:00 ± 1 h, from day 1 to day 28 of admission. The primary objective of this initial study is to assess the feasibility of conducting the proposed RCT by testing recruitment and retention rates, appropriateness of study outcome measures, acceptability of study procedures and effectiveness of the blinding process. The primary outcome measure of the proposed larger RCT is time to first inpatient incident episode of delirium. We also plan to collect data on incident rates of delirium and patient-days of delirium, adjusting for length of admission., Discussion: The outcomes of this feasibility study will provide information on recruitment and retention rates, protocol violation frequency, effectiveness of the blinding process, acceptability of the study procedures, and safety of the proposed intervention. This will inform the design of a fully powered randomized controlled trial to evaluate the preventative role of melatonin administration in patients with advanced cancer., Trial Registration: Registered with ClinicalTrials.gov: NCT02200172 Registered on 21 July 2014. Health Canada protocol number: BRI-MELAT-2013 (Final approved protocol version (Version 3): 18 June 2014) (Notice of Amended Authorization (NOA) received 14 November 2014).

Background: Older adults, especially those with cognitive impairment or dementia, frequently consume drugs with potential xerostomic effects that impair their quality of life and oral health., Objectives: The objective of this study was to determine the prevalence and analyze the possible pharmacological etiology of xerostomia in older people with or without cognitive impairment., Methods: Individuals with cognitive impairment were recruited from patients diagnosed using standardized criteria in two neurology departments in Southern Spain. A comparison group was recruited from healthcare centers in the same city after ruling out cognitive impairment. Data on oral health, xerostomia, and drug consumption were recorded in both groups. Dry mouth was evaluated using a 1-item questionnaire and recording clinical signs of oral dryness. All drugs consumed by the participants were recorded, including memantine, anticholinesterases, antipsychotics, antidepressants, and anxiolytics., Results: The final sample comprised 200 individuals with mild cognitive impairment or dementia and 156 without. Xerostomia was present in 70.5 % of participants with cognitive impairment versus 36.5 % of those without, regardless of the drug consumed. Memantine consumption was the only variable significantly related to xerostomia in the multivariate model (OR 3.1; 95 % CI 1.1-8.7), and this relationship persisted after adjusting for possible confounders and forcing the inclusion of drugs with xerostomic potential., Conclusions: More than 70 % of participants diagnosed with cognitive impairment or dementia had xerostomia. Anticholinesterases and memantine were both associated with the presence of xerostomia. In the case of memantine, this association was independent of the consumption of the other drugs considered.

The descriptive term behavioral and psychological symptoms of dementia (BPSD) is used to cover a range of noncognitive disturbances including anxiety, depression, irritability, aggression, agitation, eating disorders, and inappropriate social or sexual behaviors. Behavioral and psychological symptoms of dementia are seen in about 90% of patients with dementia. We aimed to compare the efficacy and tolerability of risperidone, yokukansan, and fluvoxamine used for BPSD in elderly patients with dementia. Ninety inpatients with dementia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria were investigated in Sato Hospital, Koutokukai. We conducted an 8-week, rater-blinded, randomized trial, administering flexibly dosed risperidone, yokukansan, or fluvoxamine. Primary outcome measures were Neuropsychiatric Inventory in Nursing Home Version total score and its items. Secondary outcome measures were cognitive function measured by Mini-Mental State Examination and daily life function measured by Functional Independence Measure (FIM). Neurological adverse effects were measured by the Drug-Induced Extra-Pyramidal Symptoms Scale. At the end of the study, we analyzed 76 patients (92.7%). Mean Neuropsychiatric Inventory in Nursing Home Version total score decreased in all 3 drug groups, with no significant between-group differences. Mini-Mental State Examination and Functional Independence Measure scores did not change significantly. Drug-Induced Extra-Pyramidal Symptoms Scale scores did not change in the yokukansan and fluvoxamine groups, but increased significantly in the risperidone group. Risperidone, yokukansan, and fluvoxamine were equally effective in the treatment of BPSD in elderly patients. However, yokukansan or fluvoxamine for BPSD showed a more favorable profile in tolerability compared with risperidone. This trial is registered at UMIN Clinical Trials Registry (identifier: UMIN000006146).

Purpose: Concomitant use of anti-dementia drugs with psychotropic drugs is potentially problematic in patients with dementia. The aim of this study was to investigate how frequently patients in Norway use anti-dementia drugs concomitantly with psychotropic drugs., Methods: Analyses are based on data from the Norwegian Prescription Database. All patients who had an anti-dementia drug (ATC-code N06D) dispensed from a Norwegian pharmacy between January 2004 and July 2009 were included., Results: A total of 33,816 individuals received anti-dementia drugs at some time during this period. The total concomitant use of anti-dementia drugs with psychotropic drugs was 57.4% in men and 65.8% in women. Compared with men, a significantly higher percentage of women used antidepressants (35.8% versus 27.2%), mild hypnotics (28.8% versus 23.6%), benzodiazepines (25.4% versus 20.8%) and opioids (22.8% versus 17.4%) concomitantly with anti-dementia drugs. Concomitant use of antipsychotics with anti-dementia drugs was about 16% for both male and female patients. Of the total sample, 11.9% of the women and 11.7% of the men used acetylcholinesterase inhibitor (AChEI) anti-dementia drugs concomitantly with an interacting psychotropic drug., Conclusion: The concomitant use of psychotropic drugs with anti-dementia drugs was extensive, especially among women. Co-medication with potentially interacting drugs occurred at a rate of one in 10. The concomitant use of anti-dementia drugs with psychotropic drugs identified in this study may inform the ongoing clinical debate about drug use in this patient group., (Copyright © 2011 John Wiley & Sons, Ltd.)

Neuropsychiatric symptoms are frequent and troublesome in people with dementia and present a major treatment challenge for clinicians. Most good practice guidelines suggest non-pharmacological treatments as the first-line therapy and there is emerging evidence, including randomized controlled trials, that a variety of psychological and training interventions, including social interaction and person-centred care training, are effective. There is evidence from meta-analyses that some atypical antipsychotic drugs, specifically risperidone and aripiprazole, confer benefit in the treatment of aggression in people with Alzheimer's disease over a period of up to 12 weeks. However, these benefits have to be considered in the context of significant adverse events, including extrapyramidal symptoms, accelerated cognitive decline, stroke and death. In addition, the limited evidence available does not indicate ongoing treatment benefits over longer periods of therapy. The evidence is limited for other pharmacological treatment approaches, but the best evidence is probably for carbamazepine, memantine and citalopram. There is very limited evidence for any therapies in non-Alzheimer dementias. In conclusion, it is important in most situations to limit the use of antipsychotic medication to short-term treatment (up to 12 weeks) of severe neuropsychiatric symptoms to limit harm. Non-pharmacological therapies offer a viable and effective alternative in many situations. Adequately powered randomized controlled trials for the treatment of clinically significant agitation are urgently needed to explore alternative pharmacological therapies.

Purpose: Old people in general, and particularly those with dementia, are more sensitive to adverse drug effects than younger people. Despite this, the use of central nervous system (CNS) drugs among old people is common. The aim of the present study was to compare the use of central nervous system drugs and analgesics among people aged 85 years or older, with and without dementia., Methods: One half of all people aged 85 years old and all those aged 90, 95 and above in Umeå, Sweden and Vaasa and Mustasaari, Finland, were asked to participate in this part of the GERDA/Umeå 85+ study. Both those living in their own homes and those in institutions were included. Trained investigators performed structured interviews and assessments. Medication data were obtained from the participants and medical records. Dementia disorders were diagnosed according to DSM-IV., Results: Dementia was diagnosed in 247/546 participants (45.2%). A higher proportion of the participants with dementia used paracetamol (50.6% compared to 21.4%, p < 0.001), antipsychotics (22.3% and 2.7%, p < 0.001), antidepressants (33.6% and 11.4%, p < 0.001) and anxiolytics (19.0% and 8.0%, p < 0.001). There were no differences in the use of opioid analgesics, anticonvulsants and hypnotics., Conclusions: The use of CNS drugs and analgesics was common among this population of very old people. Furthermore, the prescription of CNS drugs was more common among people with dementia. The use of antipsychotics in people with dementia should arouse particular concern, because of the high risk of severe adverse events and the limited evidence of positive effects.

There are no Food and Drug Administration (FDA)-approved medications for the medical management of frontotemporal dementia and its related disorders, so all management recommendations are necessarily off-label and borrowed from experience with Alzheimer's disease, psychiatric disease, and related medical illnesses. Six areas of pharmacotherapeutic consideration are prevention (primary and secondary), intellectual decline, behavioral disorders (such as depression, anxiety, and psychosis), sleep disorders, frequently associated disorders (including motor neuron disease), and abrupt decline. In addition to pharmacotherapy, important lifestyle issues confronting the clinician include driving cessation, securing any weapons maintained at home, assisted living, and caregiver burnout.

Few recent studies have investigated the prevalence and outcomes for central nervous system (CNS)-active medication use in older persons with dementia (PWD) who live in the community. Thus, the purpose of this study was to describe the health outcomes and patterns of use of CNS-active drugs in PWD living in the community. Using a retrospective study design from a southeastern managed care organization (MCO), claims data were collected for three years on all identified cases with dementia and included age, gender, medical diagnoses for each claim (International Classification of Disease [ICD-9 code]) and prescription drugs (National Drug Code [NDC]). Individuals (N = 960) were selected who were continuously enrolled and had prescription drug coverage. Over 79% of PWD in this sample were on a CNS-active medication during the three-year period and 35% were on a benzodiazepine. The highest number of drug-related problems (DRPs) within 45 days after receiving a CNS drug prescription were for syncope, fatigue, altered level of consciousness, delirium, constipation, falls and fractures. This study illustrates the need to further examine inappropriate CNS-active medication use in PWD and to test non-pharmacologic therapies for the clinical problems that initiate their use in PWD.

Nefiracetam (DM-9384) is a cerebral metabolic product under development by Daiichi for the potential treatment of the after-effects of cerebrovascular disorders. By September 1999, nefiracetam was In phase II trials in the US for the treatment of mental symptoms associated with sequelae of stroke and Alzheimer's type dementia. By August 2000, clinical trials in China had been completed in preparation for an NDA filing In November 2000, the companypredicted a launch in 2002. Modified phase III trials of the compound were being repeated in Japan in preparation for re-filing of an NDA. The protocol for the initial Japanese phase III retrial in patients with sequelae of cerebral infarction was approved at the end of July 1999, with completion of the trial expected by the end of 2000. However, in February 2002 Daiichi withdrew its Japanese NDA due to insufficient efficacy in the revised trial. In December 2001, analysts at Morgan Stanley predicted that nefiracetam would be submitted for approval in Japan in 2002, with its approval/launch taking place in late 2002 or 2003. Estimated sales in Japan of yen 3 billon in 2002, rising to yen 13 billion in 2005 and peak sales of yen 20 to 30 billion are predicted.

Pharmacological treatment strategies for the treatment in dementia disorders were described. A selection of the 15 different classes described by Fröstl and Maitre was made. In the paper there were included and described in detail the following classes: piracetam-type compounds, co-dergocrine-type compounds, vasodilators and haemorheological agents, cholinesterase inhibitors, ACTH and vasopressin analogs and angiotensin II and angiotensin converting enzyme inhibitors. Some compounds e.g. propentofylline, vincamine, THA and RA-octil were described in more detail.