Rajesh R. Tampi

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.

Frontotemporal dementia: latest evidence and clinical implications:

Background: Frontotemporal dementia (FTD) describes a cluster of neurocognitive syndromes that present with impairment of executive functioning, changes in behavior, and a decrease in language proficiency. FTD is the second most common form of dementia in those younger than 65 years and is expected to increase in prevalence as the population ages. This goal in our review is to describe advances in the understanding of neurobiological pathology, classification, assessment, and treatment of FTD syndromes. Methods: PubMed was searched to obtain reviews and studies that pertain to advancements in genetics, neurobiology, neuroimaging, classification, and treatment of FTD syndromes. Articles were chosen with a predilection to more recent preclinical/clinical trials and systematic reviews. Results: Recent reviews and trials indicate a significant advancement in the understanding of molecular and neurobiological clinical correlates to variants of FTD. Genetic and histopathologic markers have only recently been discovered in the past decade. Current therapeutic modalities are limited, with most studies reporting improvement in symptoms with nonpharmacological interventions. However, a small number of studies have reported improvement of behavioral symptoms with selective serotonin reuptake inhibitor (SSRI) treatment. Stimulants may help with disinhibition, apathy, and risk-taking behavior. Memantine and cholinesterase inhibitors have not demonstrated efficacy in ameliorating FTD symptoms. Antipsychotics have been used to treat agitation and psychosis, but safety concerns and side effect profiles limit utilization in the general FTD population. Nevertheless, recent breakthroughs in the understanding of FTD pathology have led to developments in pharmacological interventions that focus on producing treatments with autoimmune, genetic, and molecular targets. Conclusion: FTD is an underdiagnosed group of neurological syndromes comprising multiple variants with distinct neurobiological profiles and presentations. Recent advances suggest there is an array of potential novel therapeutic targets, although data concerning their effectiveness are still preliminary or preclinical. Further studies are required to develop pharmacological interventions, as there are currently no US Food and Drug administration approved treatments to manage FTD syndromes.

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.

Antipsychotics, Antidepressants, Anticonvulsants, Melatonin, and Benzodiazepines for Behavioral and Psychological Symptoms of Dementia: a Systematic Review of Meta-analyses

Opinion statementThe purpose of this systematic review is to evaluate the data on the use of antipsychotics, antidepressants, anticonvulsants, melatonin, and benzodiazepines for the treatment of behavioral and psychological symptoms of dementia (BPSD) from meta-analyses. We performed a literature search of PubMed, MEDLINE, EMBASE, PsycINFO, and Cochrane collaboration databases through August 31, 2016 using the following keywords: dementia, meta-analysis, antipsychotics, antidepressants, anticonvulsants, melatonin, and benzodiazepines. We found a total of 24 meta-analyses that assessed the use of antipsychotics, antidepressants, anticonvulsants, melatonin, and benzodiazepines among individuals with dementia. Sixteen of these meta-analyses evaluated the use of antipsychotics among individuals with dementia. One of the 16 meta-analyses not only evaluated the use of antipsychotics but also antidepressants and mood stabilizers for BPSD. A total of three meta-analyses assessed the use of antidepressants among individuals with dementia, two meta-analyses evaluated the use of mood stabilizers, two meta-analyses evaluated the use of melatonin, and one meta-analysis evaluated the use of melatonin, trazodone, and ramelteon for sleep disturbances among individuals with dementia. There was no meta-analysis for the use of benzodiazepines among individuals with dementia. Data from this systematic review indicates that antipsychotics demonstrate modest efficacy in the treatment of BPSD. Antidepressants appear to improve symptoms of depression among individuals with dementia and may improve some behavioral symptoms among these individuals. Anticonvulsants appear to have no beneficial effects when used in individuals with dementia. Melatonin appears to improve some sleep parameters and some behavioral symptoms among these individuals. Trazodone appears to improve some sleep parameters among individuals with dementia but has not demonstrated efficacy in managing BPSD. The use of antipsychotics and anticonvulsants in this population is limited by their adverse effect profile.

The Treatment of Behavioral and Psychological Symptoms of Dementia: Weighing Benefits and Risks

Behavioral and psychological symptoms of dementia (BPSD) are common among patients with dementia. BPSD have significant implications on outcomes for patients and caregivers. Available literature for pharmacological approaches to BPSD is sparse and at times inconsistent. There are no FDA-approved medications for the management of BPSD, and the use of available medications is associated with significant adverse effects among aged populations with dementia. This review outlines the assessment of BPSD, discusses general principles of management, and examines current evidence for non-pharmacologic and pharmacologic treatment strategies as well as associated risks.

Pharmacotherapy for Late-Life Depression with Psychotic Features: A Review of Literature of Randomized Control Trials

Depression in not uncommon in late life. Psychotic depression, a more severe form of depression is more common in late life than younger patients. Data indicate that approximately 25% of patients with depression in late life present with psychotic symptoms. In this review, we systematically searched four main databases; EMBASE, PsychINFO, Medline and Cochrane Collaboration on the pharmacotherapy of late life depression with psychotic features. Data for the treatment of psychotic depression in late life are scares although available evidence indicates efficacy for antidepressants, antipsychotic medications and mifepristone and electroconvulsive therapy. Based on the available evidence, we have provided a guideline for the appropriate treatment of this important disorder thus preventing undue suffering to the patients and their families.

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.

Prazosin in Children and Adolescents With Posttraumatic Stress Disorder Who Have Nightmares: A Systematic Review.

Background The aim of this systematic review was to identify published articles that evaluated the use of prazosin for treating nightmares in children and adolescents who have posttraumatic stress disorder (PTSD). Procedures A literature search was conducted of PubMed, MEDLINE, EMBASE, Cochrane Collaboration, and PsycINFO databases for published articles in any language that evaluated the use of prazosin for treating nightmares in the context of PTSD in children and adolescents using the following key words: PTSD, nightmares, prazosin, children, adolescents, trauma, and sleep. Results A total of 9 published articles related to the use of prazosin for treatment of nightmares in PTSD in children and adolescents were identified. Six of the 9 articles that met our inclusion criteria were case reports. All of these 6 case reports showed marked improvement in nightmares when prazosin was used, although at a generally lower dose when compared with its use in adults, with dosing ranging from 1 to 4 mg/d. Conclusions Prazosin has shown promising outcomes in treating nightmares associated with PTSD in children and adolescents, although this has not been well studied. Future placebo-controlled trials are needed to assess the efficacy and safety of prazosin in treating PTSD-related nightmares in children and adolescents.

Management of Delirium in the Elderly Patients: A Review of Evidence

Delirium is a common neuropsychiatric disorder in the elderly. Delirium often has multifactorial etiologies and the condition emerges due to the interaction between the different predisposing and precipitating factors. If delirium is left untreated, it can lead to significantly higher rates of morbidity and mortality. Unfortunately, many cases of delirium in the elderly are missed or this condition is misdiagnosed as a depressive or a neurocognitive disorder. Emerging data indicates that a significant number of cases of delirium can be prevented. Evidence indicates that both non-pharmacological and pharmacological treatment methods have shown benefit in reducing the incidence of delirium, mitigating its severity, decreasing the duration of the episode and also shortening the length of hospital stay. In this review, we discuss the evidence based prevention and the management of delirium in the elderly.

Pharmacology and Psychopharmacology

Up-to-date knowledge of pathophysiological changes associated with aging and psychopharmacology are essential skills for clinicians caring for older adults with psychiatric disorders. This knowledge enables clinicians to make optimal use of psychotropic medications to treat psychiatric disorders in the older adult population. Maximizing the effectiveness of psychotropic medications and minimizing their adverse effect profile will enable older adults to have better treatment outcomes. This optimization of treatment will reduce the financial burden on an already stretched healthcare system. In this chapter we review essential aspects of geriatric pharmacology and psychopharmacology that will enable clinicians to optimize the treatment of older adults with psychiatric disorders.