Beyond "Psychotropic": Repurposing Psychiatric Drugs for COVID-19, Alzheimer's Disease, and Cancer.

Importance: "Psychotropic" drugs have widespread reach and impact throughout the brain and body. Thus, many of these drugs could be repurposed for non-psychiatric indications of high public health impact.Observations: The selective serotonin reuptake inhibitor (SSRI) fluvoxamine was shown efficacious as a COVID-19 treatment based on randomized controlled trials (RCTs), and a benefit of other antidepressants has been posited based on observational and preclinical studies. In this review, we illuminate features of SSRIs and other psychiatric drugs that make them candidates to repurpose for non-psychiatric indications. We summarize research that led to fluvoxamine's use in COVID-19 and provide guidance on how to use it safely. We summarize studies suggestive of benefit of other antidepressants versus COVID-19 and long COVID. We also describe putative mechanisms of psychiatric drugs in treating long COVID, Alzheimer's disease, cancer, and other conditions.Conclusion and Relevance: There is a potentially great clinical and public health impact of psychotropic drug repurposing. Challenges exist to such repurposing efforts, but solutions exist for researchers, regulators, and funders that overcome these challenges.

Risk of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 mortality in people with pre-existing mental disorders: an umbrella review.

INTRODUCTION: The COVID-19 pandemic has posed a serious health risk, especially in vulnerable populations. Even before the pandemic, people with mental disorders had worse physical health outcomes compared to the general population. This umbrella review investigated whether having a pre-pandemic mental disorder was associated with worse physical health outcomes due to the COVID-19 pandemic. METHODS: Following a pre-registered protocol available on the Open Science Framework platform, we searched Ovid MEDLINE All, Embase (Ovid), PsycINFO (Ovid), CINAHL, and Web of Science up to the 6th of October 2021 for systematic reviews on the impact of COVID-19 on people with pre-existing mental disorders. The following outcomes were considered: risk of contracting the SARS-CoV-2 infection, risk of severe illness, COVID-19 related mortality risk, risk of long-term physical symptoms after COVID-19. For meta-analyses, we considered adjusted odds ratio (OR) as effect size measure. Screening, data extraction and quality assessment with the AMSTAR 2 tool have been done in parallel and duplicate. RESULTS: We included five meta-analyses and four narrative reviews. The meta-analyses reported that people with any mental disorder had an increased risk of SARS-CoV-2 infection (OR: 1.71, 95% CI 1.09-2.69), severe illness course (OR from 1.32 to 1.77, 95%CI between 1.19-1.46 and 1.29-2.42, respectively) and COVID-19 related mortality (OR from 1.38 to 1.52, 95%CI between 1.15-1.65 and 1.20-1.93, respectively) as compared to the general population. People with anxiety disorders had an increased risk of SAR-CoV-2 infection, but not increased mortality. People with mood and schizophrenia spectrum disorders had an increased COVID-19 related mortality but without evidence of increased risk of severe COVID-19 illness. Narrative reviews were consistent with findings from the meta-analyses. DISCUSSION AND CONCLUSIONS: As compared to the general population, there is strong evidence showing that people with pre-existing mental disorders suffered from worse physical health outcomes due to the COVID-19 pandemic and may therefore be considered a risk group similar to people with underlying physical conditions. Factors likely involved include living accommodations with barriers to social distancing, cardiovascular comorbidities, psychotropic medications and difficulties in accessing high-intensity medical care.

Implementing clinical guidelines for co-occurring substance use and major mental disorders in Swedish forensic psychiatry: An exploratory, qualitative interview study with mental health care staff.

INTRODUCTION: Patients with substance use disorders (SUD) and co-occurring mental disorders (COD) within forensic psychiatric care often suffer poor treatment outcomes and high rates of criminal recidivism, substance use, and psychiatric problems. This study aimed to describe the conditions for, and mental health care staff's experiences with, implementing integrated SUD-focused clinical guidelines, including assessment and treatment for patients with COD at a high-security forensic mental health services (FMHS) facility in Sweden. METHODS: Study staff conducted nineteen semi-structured interviews with health care staff experienced in administering the new SUD assessment and treatment. The study conducted a thematic analysis to describe the health care staff's experiences with these guidelines and suggestions for improvement. RESULTS: Most participants reported appreciation for the implementation of clinical guidelines with an SUD focus, an area they considered to have previously been neglected, but also noted the need for more practical guidance in the administration of the assessments. Participants reported the dual roles of caregiver and warden as difficult to reconcile and a similar, hindering division was also present in the health care staff's attitudes toward SUD. Participants' reports also described an imbalance prior to the implementation, whereby SUD was rarely assessed but treatment was still initiated. One year after the implementation, an imbalance still existed, but in reverse: SUD was more frequently assessed, but treatment was difficult to initiate. CONCLUSIONS: Despite indications of some ambivalence among staff regarding the necessity of the assessment and treatment guidelines, many participants considered it helpful to have a structured way to assess and treat SUD in this patient group. The imbalance between frequent assessment and infrequent treatment may have been due to difficulties transitioning patients across the "gap" between assessment and treatment. To bridge this gap, mental health services should make efforts to increase patients' insight concerning their SUD, flexibility in the administration of treatment, and the motivational skills of the health care staff working with this patient group. Participants considered important for enhancing treatment quality a shared knowledge base regarding SUD, and increased collaboration between different professions and between in- and outpatient services.

Association of preexisting psychiatric disorders with post-COVID-19 prevalence: a cross-sectional study.

Evidence demonstrating the association of preexisting psychiatric disorders with post-COVID-19 is limited. We aim to investigate the association using larger sample sizes and more extended postinfection periods than previous studies. A total of 6015 (response rate = 77.5%) COVID-19 survivors were surveyed using a self-administered questionnaire from July to September 2021. Poisson regression analysis with robust error variance was performed to estimate post-COVID-19 prevalence ratios (PRs) with or without preexisting psychiatric disorders. Participants with preexisting psychiatric disorders numbered 1067 (17.7%), and with post-COVID-19 were 2149 (35.7%). Post-COVID-19 PR with preexisting psychiatric disorders was 1.09 (95% CI 1.02-1.18, p = 0.013). The interaction between preexisting psychiatric disorders and postinfection periods was significant (p for interaction < 0.001). The subgroup analysis showed that those with preexisting psychiatric disorders might be at greater prolonged risk of post-COVID-19 than those without the disorders. These findings suggested that preexisting psychiatric disorders were associated with an increased post-COVID-19 risk, and post-COVID-19 with preexisting psychiatric disorders might prolong even if time passes.

Results of a Qualitative Study Aimed at Building a Programme to Reduce Cardiovascular Risk in People with Severe Mental Illness.

People with severe mental illness (PSMI) have a shorter life expectancy and are more likely to have cardiovascular disease than the general population. Patients, carers, psychiatric professionals and primary care providers can all play a role in increasing PSMI physical health. The present qualitative exploratory study aimed to explore the views of these four populations as part of the multi-phase COPsyCAT project, whose objective is to build and test a cardiovascular risk prevention programme for PSMI. Overall, 107 people participated in the study's 16 focus groups, which were transcribed and analysed in a thematic analysis. With a view to building the health promotion programme, major themes identified in the corpus were translated into a list of needs as follows: communication, information, training and support. Results show that it is essential to improve communication between all the different stakeholders in mental health. The greatest challenge facing this programme will be to adapt it to the needs and expectations of PSMI while facilitating work between the various mental health stakeholders. Simple and inexpensive actions could be taken to improve the cardiovascular health of PSMI and will be experimented with during the programme's feasibility study which will start in September 2022.

Effects of the COVID-19 pandemic on clinically diagnosed psychiatric disorders in persons with type 2 diabetes.

AIMS: To examine whether the incidence rates of diagnosed depression, anxiety disorders and stress reactions, as well as prescription rates of antidepressants and anxiolytics were higher during the COVID-19 pandemic than before in persons with type 2 diabetes in Germany. Contrary to earlier studies, clinical diagnoses of psychiatric disorders (ICD classification) were used. METHODS: The German Disease Analyzer (DA) database is an outpatient database containing routine data on patients´ diseases and treatments provided by a representative panel of physician practices selected from across Germany. We assessed incidence rates of depressive disorders (ICD-10: F32, F33), anxiety disorders (F41) and stress reactions (F43) in quarters from January 2019 to March 2021 in 95,765 people with type 2 diabetes included in the DA in 2019 (mean age 68.9 years, 58% men). Prescription rates of antidepressants and anxiolytics in quarters from January 2020 to March 2021 were compared with prescription rates from 1 year earlier. RESULTS: During the study period, the incidence rate of newly diagnosed depressive disorders in persons with type 2 diabetes declined slightly, while the incidence rates of anxiety and stress disorders remained largely constant. The rates of new prescriptions for antidepressants and anxiolytics were lower in all quarters of 2020 and in the first quarter of 2021 than in the quarters 1 year earlier. Diabetes-related complications were more prevalent in persons with incident psychiatric disorders than in those without. CONCLUSIONS: No increase in the incidence rates of clinically diagnosed psychiatric disorders was observed during the COVID-19 pandemic in Germany in persons with type 2 diabetes.

Remitting neuropsychiatric symptoms in COVID-19 patients: Viral cause or drug effect?

Numerous reports of neuropsychiatric symptoms highlighted the pathologic potential of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its relationship the onset and/or exacerbation of mental disease. However, coronavirus disease 2019 (COVID-19) treatments, themselves, must be considered as potential catalysts for new-onset neuropsychiatric symptoms in COVID-19 patients. To date, immediate and long-term neuropsychiatric complications following SARS-CoV-2 infection are currently unknown. Here we report on five patients with SARS-CoV-2 infection with possible associated neuropsychiatric involvement, following them clinically until resolution of their symptoms. We will also discuss the contributory roles of chloroquine and dexamethasone in these neuropsychiatric presentations.

Substance use, mental disorders and COVID-19: a volatile mix.

PURPOSE OF REVIEW: The COVID-19 pandemic and associated restrictions have uniquely and disproportionately affected vulnerable populations. This review summarizes recent evidence on the relationship between psychiatric disorders, substance use disorders and COVID-19, highlighting acute and long-term risks, pharmacotherapy interactions and implications regarding appropriate and timely evidence-based treatment. RECENT FINDINGS: Evidence points to a complex relationship between psychiatric and substance use disorders and COVID-19. A range of risk factors associated with psychiatric and substance use disorders increases the risk of exposure to, and complications arising from, the COVID-19 virus. COVID-19 infection has been indicated as having acute and potential long-term impacts on both psychiatric and substance use disorders. Social disruption associated with restrictions imposed to curb transmission has also been identified as a risk factor for new onset of disorders and recurrence and exacerbation of existing conditions. SUMMARY: Early recognition and intervention are key to preventing chronic disability associated with psychiatric disorders, substance use disorders, and their co-occurrence. It is critical that those most in need of services do not fall through the cracks of our healthcare systems. The pandemic has fast tracked the opportunity for widespread implementation of digital health interventions but ensuring these are accessible and available to all, including our most vulnerable, will be a critical task for our future health and social ecosystems.

Predictors of infection, symptoms development, and mortality in people with SARS-CoV-2 living in retirement nursing homes.

INTRODUCTION: Since the start of the pandemic, millions of people have been infected, with thousands of deaths. Many foci worldwide have been identified in retirement nursing homes, with a high number of deaths. Our study aims were to evaluate the spread of SARS-CoV-2 in the retirement nursing homes, the predictors to develop symptoms, and death. METHODS AND FINDINGS: We conducted a retrospective study enrolling all people living in retirement nursing homes (PLRNH), where at least one SARS-CoV-2 infected person was present. Medical and clinical data were collected. Variables were compared with Student's t-test or Pearson chi-square test as appropriate. Uni- and multivariate analyses were conducted to evaluate variables' influence on infection and symptoms development. Cox proportional-hazards model was used to evaluate 30 days mortality predictors, considering death as the dependent variable. We enrolled 382 subjects. The mean age was 81.15±10.97 years, and males were 140(36.7%). At the multivariate analysis, mental disorders, malignancies, and angiotensin II receptor blockers were predictors of SARS-CoV-2 infection while having a neurological syndrome was associated with a lower risk. Only half of the people with SARS-CoV-2 infection developed symptoms. Chronic obstructive pulmonary disease and neurological syndrome were correlated with an increased risk of developing SARS-CoV-2 related symptoms. Fifty-six (21.2%) people with SARS-CoV-2 infection died; of these, 53 died in the first 30 days after the swab's positivity. Significant factors associated with 30-days mortality were male gender, hypokinetic disease, and the presence of fever and dyspnea. Patients' autonomy and early heparin treatment were related to lower mortality risk. CONCLUSIONS: We evidenced factors associated with infection's risk and death in a setting with high mortality such as retirement nursing homes, that should be carefully considered in the management of PLRNH.

Establishing a COVID-positive mental health ward: an Australian-first case study.

OBJECTIVE: Managing mental health patients during the COVID-19 pandemic has been a global challenge. Current workforce arrangements tend to separate those skilled in caring for highly infectious medical patients from those whose specialism is in managing co-morbid mental health, substance misuse and/or behaviours of concern, including potential non-compliance with community or health care directives. This paper reports an innovative service development through the emergency establishment of a temporary COVID-positive mental health ward in response to a local outbreak in Melbourne. METHOD: A case study of service reorientation is presented, examining barriers and enablers to effective care of co-morbid mental illness, addiction and COVID-19. RESULTS: Establishing a skilled multidisciplinary workforce across mental health and infectious disease is the most important consideration in optimising care. Other issues included suitable physical space, security arrangements and inter-disciplinary communication. CONCLUSIONS: The paper holds insights for managing mental health care during potential future infectious disease outbreaks across the country.

Mental Health and Substance Use Associated with Hospitalization among People with COVID-19: A Population-Based Cohort Study.

This study identified factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia. The study used data from the BC COVID-19 Cohort, which integrates data on all COVID-19 cases with data on hospitalizations, medical visits, emergency room visits, prescription drugs, chronic conditions and deaths. The analysis included all laboratory-diagnosed COVID-19 cases in British Columbia to 15 January 2021. We evaluated factors associated with hospital admission using multivariable Poisson regression analysis with robust error variance. Of the 56,874 COVID-19 cases included in the analysis, 2298 were hospitalized. Factors associated with increased hospitalization risk were as follows: male sex (adjusted risk ratio (aRR) = 1.27; 95% CI = 1.17-1.37), older age (p-trend < 0.0001 across age groups increasing hospitalization risk with increasing age [aRR 30-39 years = 3.06; 95% CI = 2.32-4.03, to aRR 80+ years = 43.68; 95% CI = 33.41-57.10 compared to 20-29 years-old]), asthma (aRR = 1.15; 95% CI = 1.04-1.26), cancer (aRR = 1.19; 95% CI = 1.09-1.29), chronic kidney disease (aRR = 1.32; 95% CI = 1.19-1.47), diabetes (treated without insulin aRR = 1.13; 95% CI = 1.03-1.25, requiring insulin aRR = 5.05; 95% CI = 4.43-5.76), hypertension (aRR = 1.19; 95% CI = 1.08-1.31), injection drug use (aRR = 2.51; 95% CI = 2.14-2.95), intellectual and developmental disabilities (aRR = 1.67; 95% CI = 1.05-2.66), problematic alcohol use (aRR = 1.63; 95% CI = 1.43-1.85), immunosuppression (aRR = 1.29; 95% CI = 1.09-1.53), and schizophrenia and psychotic disorders (aRR = 1.49; 95% CI = 1.23-1.82). In an analysis restricted to women of reproductive age, pregnancy (aRR = 2.69; 95% CI = 1.42-5.07) was associated with increased risk of hospital admission. Older age, male sex, substance use, intellectual and developmental disability, chronic comorbidities, and pregnancy increase the risk of COVID-19-related hospitalization.

Japanese local government management of compulsory hospitalization for patients with mental disorders and comorbid COVID-19.

Administering medical treatment or managing quarantine for a patient is particularly difficult when a patient harming others or causing self-harm because of severe depression, a manic state, or psychomotor agitation is also infected with COVID-19. Kanazawa University Hospital is the only facility able to manage such difficult cases occurring in Ishikawa prefecture, a local administrative area in Japan. The hospital has arranged a negative pressure apparatus in a psychiatric ward with two protection rooms. This report describes an urgently established but viable system in one prefecture of Japan for treating COVID-19-infected patients with severe psychiatric symptoms during the COVID-19 pandemic.