Update on Cognitive Enhancers Among the Older Adult Population: A Clinical Review.

PURPOSE OF REVIEW: The purpose of this review is to identify key classes of medications that are used for the treatment of older adults with neurocognitive disorders. RECENT FINDINGS: Clinical factors play a critical role in the prescribing of these medication classes for the treatment of dementia. The variation in prescribing trends is determined by the presence of medical and psychiatric comorbidities commonly occurring in older adults and is based on the consideration of potential interactions between pharmacotherapies for the comorbidities and for the dementia. Six medication classes currently exist to address the neurocognitive aspect of dementia, with varying pharmacokinetic and pharmacodynamic profiles. We review these six classes in this report and provide a provision of clinical insights regarding the use of these agents. While literature exists on the safety and efficacy of individual medication options for the treatment of dementia in the older adult population, further research is needed to provide clearer guidance regarding the specific use of these agents in clinical practice.

Should Antipsychotics' Risks Be Accepted by Clinicians on Behalf of Patients to Achieve Benefits of Mitigating Older Adults' Behavioral Symptoms in Short-Staffed Units?

This commentary on a case considers risks and benefits of pharmacological and nonpharmacological management of agitation in patients with dementia. Specifically, it considers beneficence and nonmaleficence in treatment decisions that affect both patients and staff as well as autonomy and surrogate decision making.

World Psychiatric Association-Asian Journal of Psychiatry Commission on Psychiatric Education in the 21st century.

Psychiatric practice faces many challenges in the first quarter of 21st century. Society has transformed, as have training requirements and patient expectations, underlining an urgent need to look at educational programmes. Meanwhile, awareness has grown around psychiatric disorders and there are evolving workforce trends, with more women going to medical school and specialising in psychiatry. Trainee psychiatrists carry different expectations for work-life balance and are increasingly becoming conscious of their own mental health. A tendency to see health as a commodity and the litigious nature of society has elicited additional pressures for healthcare professionals. Cartesian mind-body dualism has created further complexity and this can often be frustrating for patients and care-partners alike. In many cultures across Asia and beyond, patients can present with physical symptoms to express underlying psychological distress with increasing physical investigations. Simultaneously, in various countries, a shift from asylums to community-based interventions and then home treatments have changed psychiatric care in remarkable ways. These changes have added to pressures faced by mental healthcare professionals. However, trainees and other mental healthcare professionals continue to receive similar training as they did a generation ago. The tensions and differences in ideology/orientation between different branches of psychiatry have made responses to patient needs challenging. Recognising that it is difficult to predict the future, this World Psychiatric Association-Asian Journal of Psychiatry Commission makes recommendations that could help institutions and individuals enhance psychiatric education. This Commission draws from existing resources and recent developments to propose a training framework for future psychiatrists.

Suicidal Ideation and Suicide-Attempt-Related Hospitalizations among People with Alzheimer's Disease (AD) and AD-Related Dementias in the United States during 2016-2018.

People living with Alzheimer's disease (AD) and AD-related dementias (ADRDs) are at a higher risk of suicidal behaviors given intersecting risk factors. Previous studies generally only focused on AD, small clinical samples, or grouped all dementia subtypes together, limiting insights for other ADRD subtypes. The objective of this study was to generate evidence related to the relative burden of suicidal behaviors (suicidal ideation and suicide attempt) among people with AD and ADRDs. This retrospective cross-sectional study identified hospitalizations related to suicidal behaviors (suicidal ideation and suicide attempt) for patients with Alzheimer's disease (AD) and AD-related dementias using ICD-10-CM codes from the Nationwide Readmissions Database (NRD). A logistic regression model was estimated to assess associations between AD/ADRD subtype and patient characteristics, and the risk for a suicidal-behavior-related hospitalization and modes of harm were reported. During 2016-2018, there were 12,538 hospitalizations related to suicidal behaviors for people with AD/ADRDs. The overall prevalence of suicidal-behavior-related hospitalizations was lowest for AD (0.8%) and highest for frontotemporal dementia (2.6%). Among hospitalizations for suicide attempts, the most common mode of harm was medications or drugs (89.2% of all attempts), followed by weapons (17.7%). We found that there was a difference in the frequency of suicidal-behavior-related hospitalizations among AD/ADRD hospitalized patients across dementia subtypes.

Psychosis.

PURPOSE OF REVIEW: Psychosis can manifest in primary psychotic disorders, neurologic diseases, and medical conditions. This article reviews the definition of psychotic symptoms and the evaluation and management of psychosis in primary psychiatric and neurologic disorders frequently seen in neurologic practice. RECENT FINDINGS: Emerging evidence supports significant connections between psychosis and structural and functional brain changes in both primary psychotic and neurologic disorders. In addition to antidopaminergic activity, the mechanism of new-generation antipsychotics shifts to act on serotonin receptors, which potentially contributes to their benefits in the treatment of negative symptoms of psychosis and a lesser frequency of extrapyramidal side effects compared with typical antipsychotics. This is also helpful in the treatment of psychosis in patients who have neurodegenerative diseases and are vulnerable to developing extrapyramidal side effects from typical antipsychotics. SUMMARY: Even with significant overlap, management of psychosis in primary psychotic disorders differs from the approach of psychosis in neurologic diseases. This article helps clinicians learn how to practically evaluate psychosis from both psychiatric and neurologic perspectives.

Mood Disorders.

PURPOSE OF REVIEW: This comprehensive review of mood disorders brings together the past and current literature on the diagnosis, evaluation, and treatment of the depressive and bipolar disorders. It highlights the primary mood disorders and secondary neurologic causes of mood disorders that are commonly encountered in a clinical setting. As the literature and our understanding evolve, recent additions to the current literature are important to bring forth to the readers. RECENT FINDINGS: Advancements in clinical medicine have strengthened our understanding of the associations of neurologic and psychiatric diseases. This article highlights the medications frequently used with newly identified mood disorders and the common side effects of these medications. A paradigm shift has moved toward newer treatment modalities, such as the use of ketamine, repetitive transcranial magnetic stimulation, and complementary and alternative medicine. The risks and benefits of such therapies, along with medications, are reviewed in this article. SUMMARY: Mood disorders are extraordinarily complex disorders with significant association with many neurologic disorders. Early identification of these mood disorders can prevent significant morbidity and mortality associated with them. With further expansion of pharmacologic options, more targeted therapy is possible in improving quality of life for patients.

Training hospital inpatient nursing to know (THINK) delirium: A nursing educational program.

BACKGROUND/OBJECTIVES: Recognition and documentation of delirium is a challenge in the hospital. Education programs lack standardized screening tools. The presence of dementia or depression contribute to poor recognition of delirium. Many front-line healthcare workers attribute delirium to dementia, often misidentifying or delaying a correct diagnosis and in turn, treatment. Unrecognized and untreated delirium is costly. Non-pharmacologic interventions improve patient outcomes and decrease costs. Without delirium education, nurses are vulnerable to injury and low job satisfaction when caring for delirious patients. We describe an education program improving recognition and attitudes towards patients experiencing delirium. DESIGN: An education program about screening, documenting, and treating delirium. SETTING: A large Veterans Health System Hospital. PARTICIPANTS: Healthcare professionals(n = 389) participated in the education program. 355 Nurses and patient-care assistants took the pre and post-test, and 43 returned the post program follow-up survey. A delirium education program with three steps; 1) self-directed online module; 2) dementia simulation experience; and 3) a multi-station delirium skills fair. Pre and post-tests were conducted after step 2, as well as a four-month follow-up survey. MEASUREMENTS: Changes in attitude toward patients with cognitive impairment and their abilities. Self-assessment of attitudes toward patients with delirium. RESULTS: Statistically significant differences in pre and post-testing suggested increased understanding of the experience and abilities of people experiencing cognitive impairment . The four-month follow-up survey showed a continued understanding of the importance of recognizing, documenting, and treating delirium. CONCLUSION: Nursing Education about delirium that includes instruction on a standardized screening tool, documentation, and non-pharmacologic interventions improved knowledge and recognition of delirium and may have changed attitudes surrounding delirium in the hospital.

Are Patients With Schizophrenia Better Off With Lifetime Antipsychotic Medication?: Replication of a Naturalistic, Long-Term, Follow-Up Study of Antipsychotic Treatment.

PURPOSE/BACKGROUND: The question of whether people with schizophrenia should be treated with antipsychotics for life has been debated for decades. We recently reported results of 2 retrospective long-term naturalistic studies examining the association of medication adherence and global outcomes in different demographic samples. In both, we found that patients with a history of better adherence to antipsychotic medication had better quality of life outcomes. Using similar methodology, here we present such associations for a very different sample-patients with chronic schizophrenia with a long past history of antipsychotic treatment that had been treated for 19 to 53 years in a Veterans Affairs clinic. METHODS: This is a retrospective, naturalistic, longitudinal 19- to 53-year (mean average, 33.5 years) lifetime follow-up of a consecutive series of patients with schizophrenia, who had at least 8 years of antipsychotic treatment. Lifetime data were collected on (1) their medication adherence, (2) long-term global outcome, and (3) life satisfaction. Outcomes were rated by 2 different clinicians, one with information on medication adherence (nonblind rater) and one without (blind rater). Linear regression models, adjusted for age, family support, substance use disorder, race, marital status, and number of years in treatment were used to estimate the association between adherence and each outcome. RESULTS: A total of 20 patients were assessed. Medication adherence was positively associated with the blind clinician's rating of global outcome (P = 0.049) and the Global Assessment of Functioning (P = 0.021). In the nonblinded clinician's rating, medication adherence was positively related to global outcome (P = 0.001) and to the patient's report of life satisfaction (P = 0.028). IMPLICATIONS/CONCLUSIONS: This replication study, together with our previous 2 studies, is consistent with the recommendation for continuous, long-term treatment for chronic schizophrenia over many years of a patient's lifetime unless medically contraindicated.

When you hear hoofbeats, think horses and zebras: The importance of a wide differential when it comes to frontotemporal lobar degeneration.

Frontotemporal lobar degeneration (Frontotemporal dementia in DSM 4/FTD) is a progressive brain disease which frequently presents with neuropsychiatric symptoms. Prevalence of FTD is low, however the prognosis is poor. Early identification of FTD may improve quality of life, minimize behavioral disturbances and help with end of life planning. Diagnosis of FTD is often a diagnostic challenge as it has wide differentials. Authors discuss three clinical cases with their initial clinical presentation, diagnostic complexity and subsequent management.

Pharmacotherapy for the treatment of tardive dyskinesia in schizophrenia patients.

INTRODUCTION: Tardive dyskinesia (TD) is an iatrogenic movement disorder most commonly observed in patients with psychotic disorders who are treated with dopamine blocking antipsychotic medications. Treatment options are limited, and recommendations for treatment are based on a relative scarcity of evidence. Areas covered: After briefly highlighting current mechanistic theories of TD, this review will discuss the evidence for a number of medications of several different classes that have been studied for the treatment of TD since the 1970s with an emphasis on placebo controlled trials when possible. We used a Pubmed search of primary studies, reviews, and metaanalyses on the topic of TD treatment in order to cover this topic. Expert opinion: Treatment of TD is difficult given limited data and incomplete understanding of the mechanism. Treatment of TD must be evaluated on an individual basis with careful weight given to severity of symptoms. We suggest the use of atypical versus conventional antipsychotics whenever possible and would recommend trials with one or more of a number of additional agents starting with valbenazine.

Pros and Cons of Medical Cannabis use by People with Chronic Brain Disorders.

BACKGROUND: Cannabis is the most widely used illicit drug in the world and there is growing concern about the mental health effects of cannabis use. These concerns are at least partly due to the strong increase in recreational and medical cannabis use and the rise in tetrahydrocannabinol (THC) levels. Cannabis is widely used to self-medicate by older people and people with brain disorders such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), bipolar disorder, and schizophrenia. OBJECTIVE: This review provides an overview of the perceived benefits and adverse mental health effects of cannabis use in people with ALS, MS, AD, PD, bipolar disorder, and schizophrenia. RESULTS: The reviewed studies indicate that cannabis use diminishes some symptoms associated with these disorders. Cannabis use decreases pain and spasticity in people with MS, decreases tremor, rigidity, and pain in people with PD, and improves the quality of life of ALS patients by improving appetite, and decreasing pain and spasticity. Cannabis use is more common among people with schizophrenia than healthy controls. Cannabis use is a risk factor for schizophrenia which increases positive symptoms in schizophrenia patients and diminishes negative symptoms. Cannabis use worsens bipolar disorder and there is no evidence that bipolar patients derive any benefit from cannabis. In late stage Alzheimer's patients, cannabis products may improve food intake, sleep quality, and diminish agitation. CONCLUSION: Cannabis use diminishes some of the adverse effects of neurological and psychiatric disorders. However, chronic cannabis use may lead to cognitive impairments and dependence.

Transcranial Direct Current Stimulation Use in the Treatment of Neuropsychiatric Disorders: A Brief Review.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has grown in popularity over the past two decades as an alternative treatment option for various neuropsychiatric disorders. tDCS modulates cortical excitability through the application of a weak direct current to the scalp via electrodes placed over cortical regions of interest. It has been shown to be a promising and relatively safe treatment tool with few adverse events. In this article, we will briefly review the efficacy of tDCS in depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder. We will also discuss biomarkers of tDCS efficacy in depression, as it is the most studied neuropsychiatric disorder using tDCS application. We will then offer suggestions for future directions. Although efficacy results show promise, more studies with larger samples and longer treatment periods are needed to better understand the benefits of using tDCS as an alternative treatment option for neuropsychiatric disorders.

Lurasidone in the treatment of schizophrenia: a critical evaluation.

INTRODUCTION: Antipsychotic medications are the foundation of the pharmacological treatment of schizophrenia and lurasidone is the most recent of the 65 agents around the world to become available. In order to use it optimally, it is important to understand its pharmacological and clinical nature and its comparative effectiveness to other antipsychotic agents in the treatment of schizophrenia. AREAS COVERED: Following a comprehensive review of the literature, this article summarizes current information about the pharmacology of lurasidone, data about its short- and long-term efficacy and safety/tolerability in the treatment of schizophrenia, its comparative effectiveness to other antipsychotic agents, and guidance about its optimal use in the treatment of individuals with schizophrenia. EXPERT OPINION: Lurasidone is a benzoisothiazole with potent dopamine D2 and serotonin 5HT2A antagonist and serotonin 5HT1A partial agonist properties (like other second-generation antipsychotic agents) with additional potent 5HT7 and alpha2C noradrenergic antagonism. It has little or no activity at the alpha1 and alpha2A noradrenergic, 5HT2C serotonergic, histaminergic and cholinergic receptors. Available only in an oral formulation, it is effective in once-daily dosing (40 - 160 mg/day) and its absorption is affected by food. There is an extensive clinical trial database with short-term and long-term placebo- and antipsychotic-controlled clinical trials evaluating the efficacy and safety/tolerability of lurasidone in the treatment of schizophrenia. It has been found to be efficacious with comparable efficacy to other agents in the treatment of acute psychosis and prevention of relapse in individuals with schizophrenia. The greater antidepressant and cognitive benefits suggested by its receptor profile need substantiation in robust clinical trials. It is less likely to cause metabolic and cardiac adverse effects than most other second-generation agents and is associated with a modest risk of extrapyramidal side-effects, akathisia, and prolactin elevation.

Antipsychotic treatment of schizophrenia: an update.

The primary objectives in the treatment of schizophrenia are to reduce the frequency and severity of psychotic exacerbation, ameliorate a broad range of symptoms, and improve functional capacity and quality of life. Treatment includes pharmacotherapy and a range of psychosocial interventions. Antipsychotics are the cornerstone of pharmacological treatment for schizophrenia. The sixty-five antipsychotics available in the world are classified into two major groups: first-generation (conventional) agents (FGAs) and second-generation (atypical) agents (SGAs). Whereas clozapine is found to be more efficacious than other agents among otherwise treatment-refractory schizophrenia patients, other differences in efficacy between antipsychotic agents are minor. There are, however, pronounced differences in adverse effect profiles among the 65 antipsychotic medications. Although the 14 SGAs differ "on average" from the 51 FGAs in terms of being associated with a lower risk of EPS and greater risk of metabolic side-effects, substantial variation within the two classes with regard to both risks and other relevant clinical properties undermines the categorical distinction between SGAs and FGAs. Choice of antipsychotic medication should be based on prior treatment response, individual preference, medical history and individual patient vulnerabilities. An individualized treatment approach with ongoing risk-benefit monitoring and collaborative decision-making is outlined. Even as rapid neuroscience advances promise revolutionary improvements in the future, a thoughtful and disciplined approach can provide enhanced outcomes for all schizophrenia patients today.

Mobilization strategies for the collection of peripheral blood progenitor cells: Results from a pilot study of delayed addition G-CSF following chemotherapy and review of the literature.

OBJECTIVE: Given the potential to limit cost, we conducted a pilot study evaluating delayed, low-dose granulocyte colony-stimulating factor (G-CSF) following chemotherapy for the procurement of peripheral blood progenitor cells (PBPCs) for autologous transplantation and reviewed the relevant literature. PATIENTS AND METHODS: Twenty-eight patients with various malignancies received cyclophosphamide 4 gm/m(2) and paclitaxel 170 mg/m2 followed by G-CSF 300 microg/d or 480 microg/d starting day +5 until two to four daily large volume leukapheresis yielded > or =5.0 x 10(6) CD34+ cells. We searched MEDLINE, Pubmed, and EMBASE databases from 1990 to the present to identify papers on PBPC procurement using delayed G-CSF (starting day +4 or later) following chemotherapy. RESULTS: G-CSF was administered for a median of 9 days at an average cost of 1260 USD per 70-kg patient. Collection was initiated at a median of 12 days after chemotherapy. A median 2.5 (range 2-4) apheresis were performed yielding an average daily CD34+ collection of 6.9 x 10(6)/kg (range 0.35-56.7). After one apheresis, 82% and 57% of patients collected > or =2.5 x 10(6)/kg and > or =5.0 x 10(6)/kg, respectively. Ultimately, 89% collected > or =5.0 x 10(6)/kg. Febrile neutropenia and catheter-related infection developed in five and two patients, respectively. All patients proceeded to transplantation and engrafted successfully with a median of 14.9 x 10(6)/kg (range 1.05-113) cells infused. Eleven published reports were identified involving 590 patients of whom 498 received G-CSF at a dose range of 250 microg/d to 10 microg/kg/d starting day +4 to 15 for a period of 4 to 9 days for PBPC procurement. Among these reports, 62 to 100% and 33 to 96% of patients collected > or =2 to 2.5 x 10(6) and > or =5.0 x 10(6) CD34+ cells, respectively. CONCLUSION: The use of delayed, low-dose G-CSF plus chemotherapy for stem cell mobilization was feasible and provides further evidence supporting this potentially cost-effective strategy. A review of the literature supports our findings and emphasizes the need for larger studies to address this issue.

A phase II study of thalidomide in advanced metastatic renal cell carcinoma.

OBJECTIVES: To evaluate the toxicity and activity of thalidomide in patients with advanced metastatic renal cell cancer and to measure changes of one angiogenic factor, vascular endothelial growth factor (VEGF)165, with therapy. PATIENTS AND METHODS: 29 patients were enrolled on a study of thalidomide using an intra-patient dose escalation schedule. Patients began thalidomide at 400 mg/d and escalated as tolerated to 1200 mg/d by day 54. Fifty-nine per cent of patients had had previous therapy with IL-2 and 52% were performance status 2 or 3. Systemic plasma VEGF165 levels were measured by dual monoclonal ELISA in 8 patients. RESULTS: 24 patients were evaluable for response with one partial response of 11 months duration of a patient with hepatic and pulmonary metastases (4%), one minor response, and 2 patients stable for over 6 months. Somnolence and constipation were prominent toxicities and most patients could not tolerate the 1200 mg/day dose level. Systemic plasma VEGF165 levels did not change with therapy. CONCLUSION: These results are consistent with a low level of activity of thalidomide in renal cell carcinoma. Administration of doses over 800 mg/day was difficult to achieve in this patient population, however lower doses were practical. The dose-response relationship, if any, of thalidomide for renal cell carcinoma is unclear.