Is there evidence for using anticonvulsants in the prevention and/or treatment of delirium among older adults?

OBJECTIVE: This systematic review aims to identify published randomized controlled trials (RCTs) that evaluated the use of anticonvulsants for the prevention and/or treatment of delirium among older adults. METHODS: A comprehensive search of databases: MEDLINE ALL (Ovid), Embase (Ovid), PsycINFO (Ovid), Web of Science Core Collection and Cochrane Central Register of Controlled was conducted. RESULTS: The search identified four RCTs that evaluated the use of anticonvulsants among older adults with delirium. One RCT evaluated the perioperative use of gabapentin among individuals undergoing spinal surgery and the development of postoperative delirium. One RCT evaluated the relationship between the use of perioperative gabapentin and the development of postoperative delirium among individuals undergoing spinal surgery and hip and knee arthroplasty. Two post-hoc analyses of RCTs evaluated the use of gabapentin and pregabalin among individuals undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA). The perioperative use of gabapentin reduced the incidence of postoperative delirium among older adults undergoing spinal surgery. The perioperative use of gabapentin did not reduce the rates, severity or duration of postoperative delirium among older adults who were undergoing spine and hip and knee arthroplasty. The perioperative use of gabapentin did not reduce the incidence or duration of postoperative delirium among older adults undergoing elective TKA. The perioperative use of pregabalin did not reduce the incidence of postoperative delirium among older adults undergoing elective THA. Gabapentin and pregabalin were well tolerated among the individuals enrolled in these trials. There were no RCTs identified that evaluated the use of other anticonvulsants for the prevention and/or treatment of delirium among older adults. CONCLUSIONS: Based on current evidence, the routine use of anticonvulsants for the prevention and/or treatment of delirium among older adults cannot be recommended.

Systematic review of benzodiazepines for anxiety disorders in late life.

BACKGROUND: Benzodiazepines are currently the most commonly prescribed medication for the treatment of anxiety in older adults, although there is a dearth of good-quality data on this subject. The aim of this review was to systematically review studies examining the efficacy and tolerability of benzodiazepines for the treatment of anxiety disorders among older adults. METHODS: The authors conducted a systematic review, searching PubMed, Ovid MEDLINE, Ovid Embase, Web of Science, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. All searches were limited to English-language articles. The quality of each study was appraised using criteria developed by the Centre for Evidence-Based Medicine for randomized controlled trials. RESULTS: A total of 8,785 citations were retrieved and pooled in EndNote and de-duplicated to 3,753. This set was uploaded to Covidence for screening. Two separate screeners (AG and SAF) evaluated the titles, abstracts, and full text of the eligible articles. Five studies met the inclusion criteria. Across all studies, benzodiazepines were associated with decreased anxiety at the end of the study period. The limited tolerability data show mild adverse effects from the benzodiazepines studied. Limitations of the trials included limited data on the long-term use of benzodiazepines for anxiety and a preponderance of trials examining generalized anxiety disorder, with relatively less data on other anxiety disorders. CONCLUSIONS: Benzodiazepines are effective for treating anxiety disorders in late life, at least in the short term, but more data is needed to establish tolerability and their long-term benefits.

Sexuality and the Older Adult.

PURPOSE OF REVIEW: This paper provides an overview of biopsychosocial components of sexuality in older adults, sexual expression in older LGBTQ and cognitively impaired adults, and inappropriate sexual behaviors (ISBs) in dementia. RECENT FINDINGS: Sexual expression of older adults is influenced by diverse psychosocial and biologic determinants including ageist beliefs. Although the prevalence of sexual dysfunction increases with age, studies of sexual satisfaction reveal that only a minority experience significant distress. Stigma against sexual expression in LGBTQ older adults may cause concealment of sexual orientation from family or care providers due to fears of rejection. Cognitive impairment affects frequency of and satisfaction with sexual activity, as well as capacity to consent. Staff biases about sexuality can negatively impact sexual expression in healthcare settings. Dementia-related inappropriate sexual behaviors (ISBs) are common and distressing. Recent research has focused on early identification and prevention of ISB, in addition to management through non-pharmacologic and pharmacologic approaches. Sexuality remains integral to quality of life for many older adults and informed consideration of their needs is critical to healthcare delivery and institutional service planning. A comprehensive understanding of older adults' sexuality can enhance education, research, policy, and clinical care for this growing population.

Citalopram, QTc Prolongation, and Torsades de Pointes.

OBJECTIVES: The aim of this systematic review is to identify case reports of citalopram use resulting in QTc prolongation, torsades de pointes, or both, in the medical literature. METHODS: A literature search was conducted of PubMed, MEDLINE, EMBASE, Scopus, and PsycINFO databases for case reports published in any language that reported the relationship between citalopram use and the development of QTc prolongation or torsades de pointes or both. In addition, bibliographic databases of published articles were searched for additional cases. RESULTS: A total of 18 case reports of citalopram use resulting in QTc prolongation were identified. Of these, 10 cases were also associated with the development of torsades de pointes. A total of 14 cases occurred in women and 4 in men. There were 7 cases involving an overdose with citalopram. Of the 18 cases, 12 occurred in individuals who were aged <60 years and 6 were in individuals aged >60 years. In 8 of the 18 cases, the individuals were taking a dose between 20 and 60mg of citalopram in a day. Hypertension was the most common comorbid medical condition, as seen in 5 of the cases. CONCLUSIONS: QTc prolongation or torsades de pointes are infrequently reported adverse effects associated with citalopram use.

Substance Use Disorders in the Elderly.

The population of elderly in the United States with substance use disorders (SUDs) is growing appreciably. SUDs among the elderly are often associated with poor outcomes and are frequently underdiagnosed. The current diagnostic criteria are less sensitive in identifying SUDs among the elderly. Routine screening with validated screening tools may improve the diagnosis of SUDs among the elderly. There is a dearth of data from controlled studies on SUDs among the elderly and the use of pharmacologic agents for treatment, although data indicate that older adults with SUDs respond well to treatments that are specifically designed for this age group.

Prazosin for the management of behavioural and psychological symptoms of dementia.

Prazosin, a centrally acting α1 adrenoceptor antagonist, has been included in two published algorithms amongst the list of medications that may be used in the management of behavioural and psychological symptoms of dementia (BPSD). However, a review of PubMed, Ovid and Cochrane Collaboration found that there was only one small published randomized controlled trial (RCT) that evaluated the use of prazosin amongst individuals with BPSD. Evidence from this good quality RCT indicates that prazosin appears to benefit individuals with agitation and aggression amongst individuals with BPSD and this medication is well tolerated. When compared to other treatments for BPSD, including atypical antipsychotics, antidepressants, acetylcholinesterase inhibitors, memantine, repetitive transcranial magnetic stimulation and electroconvulsive therapy, where there are multiple studies for each of these treatment modalities, the data for the use of prazosin for BPSD are limited to just one good quality RCT. Given the limitations in available data, the routine use of prazosin for the treatment of BPSD cannot be recommended at this time. However, prazosin may be used for the management of agitation and aggression amongst individuals with dementia when other medication classes, like acetylcholinesterase inhibitors, memantine, antidepressants and/or atypical antipsychotics, have been ineffective or not tolerated.

Propranolol for the management of behavioural and psychological symptoms of dementia.

Propranolol is a ß-adrenergic antagonist used in the management of hypertension, cardiac arrhythmia, and angina pectoris. There is some evidence that propranolol may benefit individuals with behavioural and psychological symptoms of dementia (BPSD). A total of three case series, one randomized controlled trial and one case report were identified (from a literature search of three major databases: PubMed, Ovid, and Cochrane collaboration) that assessed the use of propranolol for the management of BPSD. From these studies, it appears that propranolol improves BPSD, including agitation and aggression. Propranolol is also well tolerated with no significant bradycardia or hypotension noted in these studies. Current data on the use of propranolol for the management of BPSD are limited in comparison to other pharmacological agents (atypical antipsychotics, antidepressants, acetylcholinesterase inhibitors, memantine, and cannabinoids) and treatment modalities (repetitive transcranial magnetic stimulation and electroconvulsive therapy). The efficacy and safety of these treatments among individuals with BPSD has been evaluated in multiple controlled studies. In clinical practice, the routine use of propranolol among people with BPSD cannot be recommended at this time given the limited data. However, propranolol can be trialled among individuals with BPSD when symptoms have not responded adequately to other medications. Propranolol may also be used prior to embarking on trials of repetitive transcranial magnetic stimulation and electroconvulsive therapy among people with BPSD given the greater acceptance of this medication in the general population.

Evidence for using dextromethorphan-quinidine for the treatment of agitation in dementia.

Behavioral and psychological symptoms including agitation are common in dementia, and are associated with decreased quality of life, increased risk of institutionalization, and greater patient and caregiver distress. Pharmacological agents used for management of behavioral and psychological symptoms of dementia are limited by their tolerability, prompting a need for identifying efficacious and safe pharmacological treatments for managing agitation in dementia. The combination of dextromethorphan and quinidine sulfate is approved for pseudobulbar affect, and may be effective in managing agitation in dementia. A review of literature found only one randomized controlled trial that evaluated the use of dextromethorphan-quinidine for the management of agitation in dementia when compared to placebo. Data from this trial demonstrated that dextromethorphan-quinidine decreased agitation in dementia, and was well tolerated. Although promising, further research is needed before dextromethorphan-quinidine combination can be accepted as a standard treatment for agitation in dementia.

Psychotic disorders in late life: a narrative review.

Psychotic disorders are not uncommon in late life. These disorders often have varied etiologies, different clinical presentations, and are associated with significant morbidity and mortality among the older adult population. Psychotic disorders in late life develop due to the complex interaction between various biological, psychological, social, and environmental factors. Given the significant morbidity and mortality associated with psychotic disorders in late life, a comprehensive work-up should be conducted when they are encountered. The assessment should not only identify the potential etiologies for the psychotic disorders, but also recognize factors that predicts possible outcomes for these disorders. Treatment approaches for psychotic disorders in late life should include a combination of nonpharmacological management strategies with the judicious use of psychotropic medications. When antipsychotic medications are necessary, they should be used cautiously with the goal of optimizing outcomes with regular monitoring of their efficacy and adverse effects.

Personality and the risk factors for developing behavioral and psychological symptoms of dementia: a narrative review.

Premorbid personality traits have been implicated as risk factors for the development of behavioral and psychological symptoms of dementia (BPSD), although there is a paucity of studies investigating this relationship. In this narrative review, a number of studies found that premorbid neuroticism has consistently been observed to have a significant association with the development of BPSD symptoms while premorbid conscientiousness, extraversion, openness and agreeableness may be protective factors against future BPSD symptoms. In conclusion, premorbid personality traits appear to affect the risk of BPSD symptoms among individuals with dementia.

Evidence for using pimavanserin for the treatment of Parkinson's disease psychosis.

The aim of this editorial is to evaluate the evidence for using pimavanserin for the treatment of Parkinson's disease psychosis (PDP) from randomized controlled trials (RCTs). We only identified two published trials that evaluated the use of pimavanserin among individuals with PDP. Both studies found that pimavanserin improved psychotic symptoms among individuals with PDP when compared to placebo. Pimavanserin was fairly well tolerated in both studies and did not appear to cause significant sedation or worsen motor symptoms among individuals with PDP. However, given the limited data, additional confirmatory studies are required before pimavanserin can be considered as a first line agent for the treatment of psychotic symptoms among individuals with PD.

Suvorexant for insomnia in older adults: a perspective review.

The aim of this review was to identify published randomized control trials (RCTs) that evaluated the efficacy and tolerability of suvorexant for the treatment of insomnia among older adults (≥65 years). A literature search was conducted of PubMed, MEDLINE, EMBASE, PsycINFO and Cochrane collaboration databases for RCTs in any language evaluating suvorexant for the treatment of insomnia in older adults. Additionally, references of full-text articles that were included in this review were searched for further studies. Data from three RCTs of suvorexant were included in this review. All the three studies fulfilled the criteria for being of good quality based on the items listed by the Center for Evidence Based Medicine (CEBM) for the assessment of RCTs. None of the three studies were conducted exclusively among older adults. However, they also included older individuals diagnosed with primary insomnia. These studies included a total of 1298 participants aged ≥65 years in age. Trial durations ranged from 3 months to 1 year. Available data from these studies indicate that suvorexant improves multiple subjective and polysomnographic sleep parameters for sleep onset and maintenance among older individuals with a diagnosis of primary insomnia and is generally well tolerated. Current evidence, although limited, indicates that suvorexant benefits older adults with primary insomnia and is generally well tolerated.

Analgesics in the management of behavioral and psychological symptoms of dementia: a perspective review.

The objective of this review was to assess the efficacy and tolerability of analgesics in reducing behavioral and psychological symptoms of dementia (BPSD) among older adults from published randomized controlled trials (RCTs). A literature search was conducted of PubMed, MEDLINE, SCOPUS, PsycINFO, and Cochrane collaboration databases for RCTs in the English language that evaluated the use of analgesics in reducing the severity of BPSD among older adults. Additionally, references of full-text articles that were included in this review were searched for extra studies. We identified a total of three unique RCTs that evaluated the use of analgesics among individuals with BPSD. One of the identified RCTs resulted in a total of three additional published papers in the literature, resulting in a total of six papers to be included in this review. All three RCTs identified some benefit for the use of analgesics in reducing BPSD. The analgesics appeared to be well tolerated in the included studies. Major study limitations include the use of data exclusively from published RCTs and limiting the search to English language publications. Additionally, we did not utilize statistical methods to evaluate the treatment outcomes including tolerability. In conclusion, available evidence although limited indicates that analgesics may reduce BPSD among some individuals with dementia living in nursing homes and are well tolerated.

Oxytocin for frontotemporal dementia: a systematic review.

BACKGROUND: The aim of this systematic review is to identify published randomized controlled trials (RCTs) that evaluated the use of oxytocin in individuals with frontotemporal dementia (FTD). METHODS: A literature search was conducted of PubMed, MEDLINE, EMBASE, PsycINFO and Cochrane collaboration databases for RCTs in any language that evaluated the use of oxytocin in individuals with FTD. Bibliographic databases of published articles were also searched for additional studies. RESULTS: A total of two RCTs that evaluated the use of oxytocin in individuals with FTD were identified. In one study, the use of oxytocin in individuals with FTD produced a reduction in identification of negative facial expressions (anger and fear) which can be hypothesized to improve trust and increase cooperation in these individuals. Both studies noted oxytocin was well tolerated and showed short term benefits on behavioral symptoms in individuals with FTD. CONCLUSIONS: Oxytocin appears to improve social aspects of cognition and behavioral symptoms in individuals with FTD and is well tolerated. However, positive data from larger and longer duration RCTs are needed before the routine use of oxytocin in individuals with FTD can be recommended.

Acetylcholinesterase Inhibitors for Delirium in Older Adults.

OBJECTIVES: The aim of this systematic review is to identify published randomized controlled trials (RCTs) that evaluated the use of acetylcholinesterase inhibitors for delirium in older adults (≥60 years). METHODS: A literature search was conducted of PubMed, MEDLINE, EMBASE, PsycINFO, and Cochrane collaboration databases for RCTs in any language that evaluated the use of acetylcholinesterase inhibitors for delirium in older adults (≥60 years). Also, bibliographic databases of the published articles were searched for additional studies. RESULTS: A total of 7 RCTs that evaluated the use of acetylcholinesterase inhibitors for delirium in older adults (≥60 years) were identified. In 5 of the 7 studies, there was no benefit for the acetylcholinesterase inhibitor in either the prevention or the management of delirium. In one study, there was a trend toward benefit for the active drug group on the incidence of delirium and the length of hospital stay, but both outcomes did not attain statistical significance. One study found a longer duration of delirium and a longer length of hospital stay in the active drug group when compared to the placebo group. The acetylcholinesterase inhibitors were well tolerated in 4 of the 7 studies. In 1 study, the mortality rate was found to be almost 3 times higher in the group receiving haloperidol and rivastigmine when compared to the group receiving haloperidol and placebo. CONCLUSION: Current evidence does not suggest efficacy of acetylcholinesterase inhibitors for the prevention or management of delirium in older adults.

Antipsychotic use in dementia: a systematic review of benefits and risks from meta-analyses.

BACKGROUND: The purpose of this review is to evaluate the data on the use of antipsychotics in individuals with dementia from meta-analyses. METHODS: We performed a literature search of PubMed, MEDLINE, EMBASE, PsycINFO and Cochrane collaboration databases through 30 November, 2015 using the following keywords: 'antipsychotics', 'dementia' and 'meta-analysis'. The search was not restricted by the age of the patients or the language of the study. However, in the final analysis we only included studies involving patients that were published in English language journals or had official English translations. In addition, we reviewed the bibliographic databases of published articles for additional studies. RESULTS: This systematic review of the literature identified a total of 16 meta-analyses that evaluated the use of antipsychotics in individuals with dementia. Overall, 12 meta-analyses evaluated the efficacy of antipsychotics among individuals with dementia. Of these, eight also assessed adverse effects. A further two studies evaluated the adverse effects of antipsychotics (i.e. death). A total of two meta-analyses evaluated the discontinuation of antipsychotics in individuals with dementia. Overall, three meta-analyses were conducted in individuals with Alzheimer's disease (AD) whereas one focused on individuals with Lewy Body Dementia (LBD). The rest of the 12 meta-analyses included individuals with dementia. CONCLUSIONS: Antipsychotics have demonstrated modest efficacy in treating psychosis, aggression and agitation in individuals with dementia. Their use in individuals with dementia is often limited by their adverse effect profile. The use of antipsychotics should be reserved for severe symptoms that have failed to respond adequately to nonpharmacological management strategies.

Melatonin and melatonin agonist for delirium in the elderly patients.

The objective of this review is to summarize the available data on the use of melatonin and melatonin agonist for the prevention and management of delirium in the elderly patients from randomized controlled trials (RCTs). A systematic search of 5 major databases PubMed, MEDLINE, PsychINFO, Embase, and Cochrane Library was conducted. This search yielded a total of 2 RCTs for melatonin. One study compared melatonin to midazolam, clonidine, and control groups for the prevention and management of delirium in individuals who were pre- and posthip post-hip arthroplasty. The other study compared melatonin to placebo for the prevention of delirium in older adults admitted to an inpatient internal medicine service. Data from these 2 studies indicate that melatonin may have some benefit in the prevention and management of delirium in older adults. However, there is no evidence that melatonin reduces the severity of delirium or has any effect on behaviors or functions in these individuals. Melatonin was well tolerated in these 2 studies. The search for a melatonin agonist for delirium in the elderly patients yielded 1 study of ramelteon. In this study, ramelteon was found to be beneficial in preventing delirium in medically ill individuals when compared to placebo. Ramelteon was well tolerated in this study.

Efficacy and tolerability of benzodiazepines for the treatment of behavioral and psychological symptoms of dementia: a systematic review of randomized controlled trials.

The objective of this review is to summarize the available data on the use of benzodiazepines for the treatment of behavioral and psychological symptoms of dementia (BPSD) from randomized controlled trials (RCTs). A systematic search of 5 major databases, PubMed, MEDLINE, PsychINFO, EMBASE, and Cochrane Collaboration, yielded a total of 5 RCTs. One study compared diazepam to thioridazine, 1 trial compared oxazepam to haloperidol and diphenhydramine, 1 trial compared alprazolam to lorazepam, 1 trial compared lorazepam to haloperidol, and 1 trial compared intramuscular (IM) lorazepam to IM olanzapine and placebo. The data indicates that in 4 of the 5 studies, there was no significant difference in efficacy between the active drugs to treat the symptoms of BPSD. One study indicated that thioridazine may have better efficacy than diazepam for treating symptoms of BPSD. In 1 study, the active drugs had greater efficacy in treating BPSD when compared to placebo. There was no significant difference between the active drugs in terms of tolerability. However, in 2 of the 5 studies, about a third of the patients were noted to have dropped out of the studies. Available data, although limited, do not support the routine use of benzodiazepines for the treatment of BPSD. But these drugs may be used in certain circumstances where other psychotropic medications are unsafe for use in individuals with BPSD or when there are significant medication allergies or tolerability issues with certain classes of psychotropic medications.