Looking in the Rearview Mirror and to the Road Ahead on Dementia & Living Well

The number of Americans living with Alzheimer's and all other dementias continues to increase. Most of them will need long-term and community-based services as the disease progresses. While medical research is making advances, there is more work to be done to ensure that every person receives care that is person-centered and allows them to live with dignity and respect.

Cognitive and negative symptoms in schizophrenia with L-Carnosine adjuvant therapy - A randomized double-blind placebo-controlled study.

The antioxidant L-Carnosine is reported to improve negative and cognitive symptoms in Schizophrenia. A randomized double-blind placebo-controlled study was planned to study the effectiveness of adjuvant L-Carnosine therapy in patients with Schizophrenia. 100 eligible patients with predominant negative symptoms as measured by scale for assessment of negative symptoms (SANS total score ≥ 60) and Schizophrenia diagnosis (International Classification of Disorder-Tenth Edition, ICD-10) were recruited. They were randomly allocated to receive a fixed dose of either 400 mg L-Carnosine or identical placebo for 3 months and increased to 800 mg from 13th week till completion of study. Primary outcome measures assessed changes in SANS scores with L-Carnosine at 24 weeks compared to baseline, 4 and 12 weeks. Secondary outcome measures were done to assess the improvement in cognitive symptoms (executive function, attention, and memory) at 24 weeks using subtests of NIMHANS (National Institute for Mental Health and Neurosciences) cognitive battery. Side effects were assessed using adverse events reporting form. The attention scores (p = .023) showed significant differences in patients receiving 800 mg of L-Carnosine at the end of the study. There were no significant differences in negative symptoms in the two arms at study completion. L-Carnosine dosing of 800 mg may be a promising agent to enhance executive functions in Schizophrenia.

Drug Interactions of Psychiatric and COVID-19 Medications

Introduction:Coronavirus disease 2019 (COVID-19) has become a pandemic with 1771514 cases identified in the world and 70029 cases in Iran until April 12, 2020. The co-prescription of psychotropics with COVID-19 medication is not uncommon. Healthcare providers should be familiar with many Potential Drug-Drug Interactions (DDIs) between COVID-19 therapeutic agents and psychotropic drugs based on cytochrome P450 metabolism. This review comprehensively summarizes the current literature on DDIs between antiretroviral drugs and chloroquine/hydroxychloroquine, and psychotropics, including antidepressants, antipsychotics, mood stabilizers, and anxiolytics.Methods:Medical databases, including Google Scholar, PubMed, Web of Science, and Scopus were searched to identify studies in English with keywords related to psychiatric disorders, medications used in the treatment of psychiatric disorders and COVID-19 medications.Results:There is a great potential for DDIs between psychiatric and COVID-19 medications ranging from interactions that are not clinically apparent (minor) to those that produce life-threatening adverse drug reactions, or loss of treatment efficacy. The majority of interactions are pharmacokinetic interactions via the cytochrome P450 enzyme system.Conclusion:DDIs are a major concern in the comorbidity of psychiatric disorders and COVID-19 infection resulting in the alteration of expected therapeutic outcomes. The risk of toxicity or lack of efficacy may occur due to a higher or lower plasma concentration of medications. However, psychiatric medication can be safely used in combination with COVID-19 pharmacotherapy with either a wise selection of medication with the least possibility of interaction or careful patient monitoring and management.

Consensus of the Liaison-Psychiatry Committee of the Colombian Psychiatric Association on the Diagnosis and Treatment of Delirium in the Context of the COVID-19 Pandemic. / Consenso del Comité de Psiquiatría de Enlace de la Asociación Colombiana de Psiquiatría sobre el diagnóstico y tratamiento del delirium en el contexto de la pandemia por COVID-19.

The pandemic caused by the new coronavirus named SARS-CoV-2 poses unprecedented challenges in the health care. Among them is the increase in cases of delirium. The severe SARS-CoV-2 disease, COVID-19, has common vulnerabilities with delirium and produces alterations in organs such as the lungs or the brain, among others, which have the potential to trigger the mental disorder. In fact, delirium may be the first manifestation of the infection, before fever, general malaise, cough or respiratory disturbances. It is widely supported that delirium increases the morbidity and mortality in those who suffer from it during hospitalization, so it should be actively sought to carry out the relevant interventions. In the absence of evidence on the approach to delirium in the context of COVID-19, this consensus was developed on three fundamental aspects: diagnosis, non-pharmacological treatment and pharmacological treatment, in patients admitted to the general hospital. The document contains recommendations on the systematic use of diagnostic tools, when to hospitalize the patient with delirium, the application of non-pharmacological actions within the restrictions imposed by COVID-19, and the use of antipsychotics, taking into account the most relevant side effects and pharmacological interactions.

Use of psychotropic drugs in the elderly in France: Are we condemned to remain at high tide?

Psychotropics are widely used drugs, especially in the elderly, especially in France. This, and the risks associated to their use, logically led to concerns that resulted in numerous studies, reports, and regulatory actions intending to limit this use. This review objective was to provide an overview of psychotropic use in elderly subjects in France for antipsychotics, antidepressants, and benzodiazepines and related drugs. The narrative review performed is structured in two parts. The first reminds the initial steps of psychotropic use monitoring in the general French population. The second provides information on psychotropic use in elderly in France using the latest open data released by the French Health Insurance system and processed using the dedicated DrugSurv tool developed within the DRUGS-SAFE® and DRUGS-SAFE® programs. This was completed examining the most recent studies regarding psychotropic use in elderly in France, whether they consisted in publications or reports. At least before the COVID-19 epidemic, decreases in psychotropic prevalence of use among the elderly in France could be observed, mostly for antipsychotics or benzodiazepines (e.g. antipsychotics, 2006-2013: 10.3% decrease and benzodiazepines 2012-2020: decrease from 30.6% to 24.7% in subjects aged ≥65). Psychotropic prevalence of use remained however very high overall (e.g. antidepressants, 2013: 13% in subjects aged 65-74 and 18% in aged ≥65), exceeding that of most other countries, with a significant proportion of inappropriate use (e.g. in 30% of benzodiazepine users, all ages) carrying a clearly identified risks for uncertain benefit. Initiatives have been multiplied at the national level to reduce psychotropic overuse in the elderly. The reported prevalences demonstrate their effectiveness is obviously insufficient. This limited effectiveness is not specific to psychotropics and might reside in a failure to create strong adherence to messages and recommendations. Other levels should be considered, especially regional, for interventions coupled with pharmacoepidemiologic monitoring allowing impact assessment.

Clozapine treatment and risk of COVID-19.

The antipsychotic clozapine is known to have immune-modulating effects. Clozapine treatment has been reported to be associated with increased risk of COVID-19 infection. However, it remains unclear whether this is because of increased testing of this patient group, who are closely monitored. We linked anonymised health records from mental health services in Cambridgeshire (UK), for patients taking antipsychotic medication, with data from the local COVID-19 testing hub. Patients receiving clozapine were more likely to be tested for COVID-19, but not to test positive. Increased testing in patients receiving clozapine suggests prudent judgement by clinicians, considering the overall health vulnerabilities of this group.

COVID-19 Vaccines and the Virus: Impact on Drug Metabolism and Pharmacokinetics.

This article reports on an American Society of Pharmacology and Therapeutics, Division of Drug Metabolism and Disposition symposium held at Experimental Biology on April 2nd, 2022, in Philadelphia. As of July 2022, over 500 million people have been infected with SARS-CoV-2 (the virus causing COVID-19) and over 12,000,000,000 vaccine doses have been administered. Clinically significant interactions between viral infections and hepatic drug metabolism were first recognized over 40 years ago during a cluster of pediatric theophylline toxicity cases attributed to reduced hepatic drug metabolism amidst an influenza B outbreak. Today, a substantive body of research supports that the activated innate immune response generally decreases hepatic cytochrome P450 (CYP) activity. The interactions extend to drug transporters and other organs and have the potential to impact drug absorption, distribution, metabolism, and excretion (ADME). Based on this knowledge, altered ADME is predicted with SARS-CoV-2 infection or vaccination. The report begins with a clinical case exploring the possibility of SARS-CoV-2 vaccination increasing clozapine levels. This is followed by discussions of how SARS-CoV-2 infection or vaccines alter the metabolism and disposition of complex drugs, such as nanoparticles and biologics and small molecule therapies. The review concludes with a discussion of the effects of viral infections on placental amino acid transport and their potential to impact fetal development. The session improved our understanding of the impact of emerging viral infections and vaccine technologies on drug metabolism and disposition, which will help mitigate drug toxicity and improve drug and vaccine safety and effectiveness. Significance Statement Altered pharmacokinetics of small molecule and complex molecule drugs and fetal brain distribution of amino acids following SARS-CoV-2 infection or immunization are possible. The proposed mechanisms involve decreased liver CYP metabolism of small molecules, enhanced innate immune system metabolism of complex molecules and altered placental and fetal blood-brain barrier amino acid transport, respectively. Future research is needed to understand the effects of these interactions on adverse drug responses, drug and vaccine safety and effectiveness and fetal neurodevelopment.

Exposure to psychotropic medications and COVID-19 course after hospital admission: Results from a prospective cohort study.

OBJECTIVE: There is evidence of a bidirectional association between COVID-19 disease and psychiatric disorders. We aimed to assess whether exposure to psychotropic medications prior to hospitalization was associated with mortality or discharge within 30 days after hospital admission. METHODS: In this prospective study, we included all individuals with a laboratory-confirmed COVID-19 infection who were admitted to the Bologna University Hospital between 1st March 2020 and 31st January 2021. We collected data about pre-existing psychiatric disorders and the use of psychotropic medications at the admission. As univariate analyses, we estimated cumulative incidence functions for 30-day mortality and discharge stratifying by exposure to each of the psychotropic medication classes. Finally, we fitted Cox regression models to estimate cause-specific Hazard Ratios (HR) of 30-day mortality and discharge. Results were adjusted for sociodemographic (age, sex), clinically relevant variables (comorbidity, c-reactive protein levels, severity of disease at presentation, history of smoking, study period), and psychiatric variables (psychiatric disorder diagnosis, number of psychotropic medications). RESULTS: Out of a total of 1238 hospitalized patients, 316 were prescribed psychotropic medications at the time of admission. Among these, 45 (3.6%) were taking a first-generation antipsychotics (FGA) and 66 (5.3%) a second generation antipsychotic (SGA). Exposure to SGA was associated with increased rates of 30-day mortality (HR = 2.01, 95%CI = 1.02-3.97) and exposure to FGA was associated with decreased rates of 30-day discharge (HR = 0.55, 95%CI = 0.33-0.90). CONCLUSION: Patients with COVID-19 infection exposed to FGA and SGA may have worse COVID-19 infection outcomes.

Psychotropic drug repurposing for COVID-19: A Systematic Review and Meta-Analysis.

Several psychotropic drugs, including antidepressants (AD), mood stabilizers, and antipsychotics (AP) have been suggested to have favorable effects in the treatment of COVID-19. The aim of this systematic review and meta-analysis was to collect evidence from studies concerning the scientific evidence for the repurposing of psychotropic drugs in COVID-19 treatment. Two independent authors searched PubMed-MEDLINE, Scopus, PsycINFO, and ClinicalTrials.gov databases, and reviewed the reference lists of articles for eligible articles published up to 13th December 2021. All computational, preclinical and clinical (observational and/or RCTs) studies on the effect of any psychotropic drug on Sars-CoV-2 or patients with COVID-19 were considered for inclusion. We conducted random effect meta-analyses on clinical studies reporting the effect of AD or AP on COVID-19 outcomes. 29 studies were included in the synthesis: 15 clinical, 9 preclinical, and 5 computational studies. 9 clinical studies could be included in the quantitative analyses. AD did not increase the risk of severe COVID-19 (RR= 1.71; CI 0.65-4.51) or mortality (RR=0.94; CI 0.81-1.09). Fluvoxamine was associated with a reduced risk of mortality for COVID-19 (OR=0.15; CI 0.02-0.95). AP increased the risk of severe COVID-19 (RR=3.66; CI 2.76-4.85) and mortality (OR=1.53; CI 1.15-2.03). Fluvoxamine might be a possible candidate for psychotropic drug repurposing in COVID-19 due to its anti-inflammatory and antiviral potential, while evidence on other AD is still controversial. Although AP are associated with worse COVID-19 outcomes, their use should be evaluated case to case and ongoing treatment with antipsychotics should be not discontinued in psychiatric patients.

Movies, stigma and choice: Evidence from the pharmaceutical industry.

Do movies reduce stigma, increasing healthcare product choices offered by firms? We provide causal evidence on this question in the context of Indian pharmaceutical markets. For unpacking these effects, we use an exogenous shock to the market due to the release of a Bollywood blockbuster movie - My Name is Khan (MNIK) where the protagonist, superstar Shahrukh Khan, suffers from Asperger's Syndrome (AS). Using a difference-in-differences design, we find a positive and statistically significant effect of MNIK (between 14% and 22% increase in variety sold and prescribed) on product differentiation and choices in the market for antipsychotic medicines used to clinically treat AS. Results are consistent using alternative controls, a placebo treatment-based test and with a variety of other robustness checks. Our findings document likely for the first-time, supply side responses to edutainment and suggests potential associated welfare effects in healthcare markets characterized by sticky demand. Implications for global health and public policy given worldwide concerns around a mental wellness epidemic with Covid-19 are discussed.

Impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic prescribing for people with dementia in nursing home settings.

OBJECTIVES: This study aimed to determine the impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic use in people with dementia living in nursing homes. METHODS: This was a comparative analysis of baseline data from two large nursing home studies, one conducted during (COVID-iWHELD study) and one prior (WHELD study) to the pandemic. It involves data from 69 and 149 nursing homes, and 1006 and 666 participants respectively. Participants were people with established dementia (score >1 on Clinical Dementia Rating Scale). Resident data included demographics, antipsychotic prescriptions and neuropsychiatric symptoms using the Neuropsychiatric Inventory Nursing Home version. Nursing home data collected were nursing home size and staffing information. RESULTS: Overall prevalence of neuropsychiatric symptoms was unchanged from pre-pandemic prevalence. Mean antipsychotic use across the sample was 32.0%, increased from 18% pre-pandemic (Fisher's exact test p < 0.0001). At a nursing home level, the medians for the low, medium and high tertiles for antipsychotic use were 7%, 20% and 59% respectively, showing a disproportionate rise in tertile three. Residents in these homes also showed a small but significant increase in agitation. CONCLUSION: There has been a significant increase in antipsychotic prescribing in nursing homes since the COVID-19 pandemic, with a disproportionate rise in one third of homes, where median prescription rates for antipsychotics were almost 60%. Strategies are urgently needed to identify these nursing homes and introduce pro-active support to bring antipsychotic prescription rates back to pre-pandemic levels.

Severity in schizophrenia patients receiving atypical antipsychotic medications

Atypical antipsychotic drugs are nowadays the mainstay of treatment of schizophrenia due to their lesser extrapyramidal symptoms (EPS) as adverse effects. However, these drugs have different profiles of adverse drug reactions (ADRs). Here, the objective of this study was to analyze the probability, occurrences, and more significant involvement of various risk factors. A prospective observational study was carried out on a patient with schizophrenia who has prescribed atypical antipsychotic drugs for their treatment. The probability of the ADR was analyzed by using the Naranjo causality assessment scale. While Glasgow antipsychotic Side effect Scale (GASS) was used to estimate the severity of side effects. Statistical software for social science (SPSS) ver 25;was used for different descriptive statistics and chi-square analysis. A total of 140 patients were included in the study of which the majority (58.57 %) was male. However, atypical antipsychotic drugs were primarily prescribed to the patient as mono therapy (81.43 %). Interestingly, COVID-19 infections were reported as positive in 39.29 % of total patients. Probability assessment of ADRs revealed that most (55 %) were "Probable". Subsequently, the GASS score was evaluated for severity, the majority (55.71 %) were reported as "Mild". The statistically significant association between gender and severity of side effects &duration of illness and severity of side effects were found (P>0.5).The Present study aids in knowing the risk factors and improving the management practices of ADR, thereby improving the guidelines in terms of safe clinical approaches for psychiatric patients.

Dementia and psychotropic medications are associated with significantly higher mortality in geriatric patients hospitalized with COVID-19: data from the StockholmGeroCovid project.

BACKGROUND: Dementia and psychotropic medications are discussed as risk factors for severe/lethal outcome of the coronavirus disease 2019 (COVID-19). We aimed to explore the associations between the presence of dementia and medication use with mortality in the hospitalized and discharged patients who suffered from COVID-19. METHODS: We conducted an open-cohort observational study based on electronic patient records from nine geriatric care clinics in the larger Stockholm area, Sweden, between February 28, 2020, and November 22, 2021. In total, we identified 5122 hospitalized patients diagnosed with COVID-19, out of which 762 (14.9%) patients had concurrent dementia and 4360 (85.1%) were dementia-free. Patients' age, sex, baseline oxygen saturation, comorbidities, and medication prescription (cardiovascular and psychotropic medication) were registered at admission. The hazard ratios (HRs) with 95% confidence intervals (CIs) of in-hospital, 30-day, 90-day, 365-day post-discharge, and overall mortality during the follow-up were obtained. Then, the associations of dementia and medication use with mortality were determined using proportional hazards regression with time since entry as a time scale. RESULTS: After adjustment, dementia was independently associated with 68% higher in-hospital mortality among COVID-19 patients compared to patients who were dementia-free at admission [HRs (95% CI) 1.68 (1.37-2.06)]. The increase was consistent post-discharge, and the overall mortality of dementia patients was increased by 59% [1.59 (1.40-1.81)]. In addition, the prescription of antipsychotic medication at hospital admission was associated with a 70% higher total mortality risk [1.70 (1.47-1.97)]. CONCLUSIONS: The clinical co-occurence of dementia and COVID-19 increases the short- and long-term risk of death, and the antipsychotics seem to further the risk increase. Our results may help identify high-risk patients in need of more specialized care when infected with COVID-19.

Rehospitalization Rates Among Patients with Psychotic Disorders During Covid-19 Pandemic: Oral Versus Long-Acting Injectable Antipsychotics.

Objective: The superiority of long-acting injectable antipsychotics (LAIs) versus oral antipsychotics is often emphasized, even in terms of adherence and rehospitaliza-tion rates. As such, LAIs are particularly recommended during the COVID-19 pandemic. The goal of our research was to determine whether there are differences in the number of rehospitalizations in patients treated for schizophrenia, schizophrenia-like disorders, and delusional states (psychotic disorders) with LAI antispychotics versus oral antispychotics. Method: Subjects with schizophrenia, schizophrenia-like disorders and delusional states participated in our retrospective study. 124 subjects were treated with oral anti-psychotics, while 72 received LAIs along with oral antipsychotics. We collected their sociodemographic data and psychiatric history data. Our main outcome measure was the number of rehospitalizations. Results: Statistical analysis showed that the studied groups did not differ according to sociodemographic parameters, except that in the group of patients with LAIs there was a significantly higher percentage of men (65 (52.4) vs 50 (69.4), p=0.029)). Also, the groups do not differ according to the psychiatric history data. There is no difference in the duration of the current hospitalization nor in the composition of the patients, considering the order of the current hospitalization. The difference in the number of rehospitalizations is not significant neither in the first year of follow-up (p=0.144), nor in the second (p=0.142), nor after two years of follow-up (p=0.083). Conclusions: Our research has shown that there is no difference in the number of rehospitalizations in patients with schizophrenia, schizophrenia-like disorders and delusional states, considering whether they take oral antipsychotics or they also take LAIs along with them. We can therefore conclude that it is particularly important to work on improving patient adherence. We must make psychiatrists aware that the pandemic, like other threats, can be our ally in improving adherence ("perceived threat as a health belief").

Psychotropic drug repurposing for COVID-19: a systematic review

Introduction: Recently, several antidepressants, mood stabilizers, and antipsychotics have been suggested to have favorable effects in the treatment of COVID-19. Objective(s): The aim of this systematic review was to collect evidence from preclinical and clinical studies concerning the scientific evidence for the repurposing of psychotropic drugs in COVID-19 treatment. Method(s): Two independent authors searched PubMed-MEDLINE, Scopus, PsycInfo, Clinical Trial Registration Site US (ClinicalTrials. gov) databases, and reviewed the reference lists of articles for eligible articles published up to May 31st, 2021. All preclinical and clinical studies on the effect of any psychotropic drug on Sars-CoV-2 or patients with COVID-19 were included. The Newcastle-Ottawa scale was used for the quality assessment of clinical studies. This systematic review adheres to the PRISMA guidelines. Result(s): 22 studies were included in the synthesis: 9 clinical studies, 9 preclinical studies, and 4 computational studies. The use of antidepressants, both SSRI and non-SSRI, was associated with a reduced risk of severe complications of COVID-19. Several antipsychotics showed an increased risk for both Sars-CoV-2 infection and severe complications during COVID-19. Conclusion(s): The current evidence supports a potential anti- SARS-CoV-2 role for several antidepressants, while the evidence on mood stabilizers or antipsychotics remains controversial. Drug repurposing proved highly successful in response to the current pandemic and psychotropic medications are widely used in clinical practice with well-known safety and tolerability profiles, showing antiviral, immunomodulatory, and anti-inflammatory properties, being perfect candidates for possible treatment of COVID-19. Further research will deliver optimized and specific therapeutic tools that will increase the preparedness of health systems for possible future epidemics.

Long-acting Injectable Antipsychotics during the COVID-19 pandemic in schizophrenia: An observational study in a real-world clinical setting.

The COVID-19 pandemic is having an important impact on the practice of mental health services and on schizophrenia patients, and heterogeneous and conflicting findings are being reported on the reduction of long-acting injectable (LAI) antipsychotics use. Aims of the study were to assess the total number of patients treated with LAI, the start of novel LAI and the discontinuation of LAI treatments, analyzing register data of the first year of the pandemic, 2020, compared to a pre-pandemic reference year, 2019. Data from two outpatient centers were retrieved, for a total of 236 participants in 2020: no significant differences were observed comparing 2020 and 2019 when considering the total number of patients on LAI treatment (p = 0.890) and the number of dropouts (p = 0.262); however, a significant reduction in the start of LAI was observed (p = 0.022). In 2020, second generation LAI were more prescribed than first generation LAI (p = 0.040) while no difference was observed in 2019 (p = 0.191). These findings attest the efficacy of measures adopted in mental health services to face the consequences of COVID-19 and shed further light on the impact of the pandemic on the clinical practice of mental health services and on the continuity of care of people with schizophrenia.

Challenges and Insights From Treating Psychotic Disorders During COVID-19 Pandemic in Brazil.

The COVID-19 pandemic mainly affected the most vulnerable individuals. Among those, patients with schizophrenia especially suffered from unexpected changes in their routines, barriers to treatment, and distress-related events. We conducted a narrative review using all available sources of information to describe the challenges faced by schizophrenia patients and their families in Brazil, including the strategies that have been adopted to tackle them. In addition, we analyzed public data on antipsychotic prescriptions and hospitalizations. It was found that digital prescriptions with extended expiration dates implemented during the pandemic in Brazil allowed patients to maintain their access to antipsychotics. Hospitalizations among patients with schizophrenia, schizotypal, and schizoaffective disorders decreased at the beginning of the pandemic. Nevertheless, in the following months, the admissions returned to a trend similar to the prepandemic period. The systematization of online resources will be one of the main legacies to mental health care, including schizophrenia. We believe one of the main limitations of the policies adopted was the decision to not prioritize COVID-19 vaccination in patients with severe psychiatric disorders, despite preliminary evidence of a higher risk of complications in this group. The coronavirus pandemic is still ongoing and a longer time will be required to have a better perspective of its effects, but we expect this record of challenges and insights about the lessons learned during the pandemic can help healthcare professionals to face similar situations in the future.