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.

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.

Rates of Antipsychotic Drug Prescribing Among People Living With Dementia During the COVID-19 Pandemic.

Importance: Concerns have been raised that the use of antipsychotic medication for people living with dementia might have increased during the COVID-19 pandemic. Objective: To examine multinational trends in antipsychotic drug prescribing for people living with dementia before and during the COVID-19 pandemic. Design, Setting, and Participants: This multinational network cohort study used electronic health records and claims data from 8 databases in 6 countries (France, Germany, Italy, South Korea, the UK, and the US) for individuals aged 65 years or older between January 1, 2016, and November 30, 2021. Two databases each were included for South Korea and the US. Exposures: The introduction of population-wide COVID-19 restrictions from April 2020 to the latest available date of each database. Main Outcomes and Measures: The main outcomes were yearly and monthly incidence of dementia diagnosis and prevalence of people living with dementia who were prescribed antipsychotic drugs in each database. Interrupted time series analyses were used to quantify changes in prescribing rates before and after the introduction of population-wide COVID-19 restrictions. Results: A total of 857 238 people with dementia aged 65 years or older (58.0% female) were identified in 2016. Reductions in the incidence of dementia were observed in 7 databases in the early phase of the pandemic (April, May, and June 2020), with the most pronounced reduction observed in 1 of the 2 US databases (rate ratio [RR], 0.30; 95% CI, 0.27-0.32); reductions were also observed in the total number of people with dementia prescribed antipsychotic drugs in France, Italy, South Korea, the UK, and the US. Rates of antipsychotic drug prescribing for people with dementia increased in 6 databases representing all countries. Compared with the corresponding month in 2019, the most pronounced increase in 2020 was observed in May in South Korea (Kangwon National University database) (RR, 2.11; 95% CI, 1.47-3.02) and June in the UK (RR, 1.96; 95% CI, 1.24-3.09). The rates of antipsychotic drug prescribing in these 6 databases remained high in 2021. Interrupted time series analyses revealed immediate increases in the prescribing rate in Italy (RR, 1.31; 95% CI, 1.08-1.58) and in the US Medicare database (RR, 1.43; 95% CI, 1.20-1.71) after the introduction of COVID-19 restrictions. Conclusions and Relevance: This cohort study found converging evidence that the rate of antipsychotic drug prescribing to people with dementia increased in the initial months of the COVID-19 pandemic in the 6 countries studied and did not decrease to prepandemic levels after the acute phase of the pandemic had ended. These findings suggest that the pandemic disrupted the care of people living with dementia and that the development of intervention strategies is needed to ensure the quality of care.

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.

Barriers to Long-acting Injectable Antipsychotic Adherence During the COVID-19 Pandemic: Observations From One Site.

OBJECTIVE: Long-acting injectable antipsychotics (LAI-As) are a crucial treatment option for individuals with serious mental illness. However, due to the necessity of in-person administration of LAI-As, pandemics pose unique challenges for continuity of care in the population prescribed these medications. This project investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic on LAI-A adherence at a Veterans Health Administration medical facility in the United States, as well as changes in LAI-A prescribing and administration practices during this period. METHODS: Electronic health records were evaluated for 101 patients prescribed LAI-As. A subset of 13 patients also participated in an interview and rated subjective concerns about pandemic-related barriers to medication adherence. RESULTS: Pandemic-related barriers to LAI-A adherence and/or changes to LAI-A medications were documented in 33% of the patients. Within-subjects comparison of an adherence metric computed from electronic health record data further suggested a somewhat higher incidence of missed or delayed LAI-A doses during the pandemic compared with before the pandemic. In contrast, only 2 of the 13 patients interviewed anticipated that pandemic-related concerns would interfere with medication adherence. CONCLUSIONS: The results of this study suggest that LAI-A access and adherence can be disrupted by pandemics and other public health emergencies but this finding may not generalize to other sites. As patients may not foresee the potential for disruption, psychiatric service providers may need to assist in proactively problem-solving barriers to access. Improved preparedness and additional safeguards against pandemic-related disruptions to LAI-A access and adherence may help mitigate adverse outcomes in the future. Identifying patients at elevated risk for such disruptions may help support these efforts.

Bipolar type I diagnosis after a manic episode secondary to SARS-CoV-2 infection: A case report.

RATIONALE: Our objective is to provide awareness about psychotic vulnerability in patients infected with SARS-CoV-2 and to better understand the role of steroid withdrawal in manic episodes, especially with its common usage in respiratory disease caused by SARS-CoV-2. PATIENT CONCERNS: We present the case of a patient who was hospitalized twice after discontinuing steroid therapy for SARS-CoV-2 infection and presented with a manic episode despite not having a psychiatric history. DIAGNOSIS: The patient tested positive on a polymerase chain reaction test for SARS-CoV-2 and developed pneumonia. Other organic differential diagnoses such as encephalitis were also investigated and excluded. Manic episodes were diagnosed according to DSM-V criteria. Subsequently, the patient was diagnosed with type I bipolar disorder. INTERVENTIONS: According to the protocols, supplemental oxygen therapy, prophylactic enoxaparin and intravenous (IV) steroids were administered. Steroid dosage was gradually reduced under supervision. During the acute mania, antipsychotics and benzodiazepines were administered. OUTCOMES: After discharge, the patient was admitted to the psychiatric consultation service. He first received mood stabilizer therapy and then received supportive psychotherapy. LESSONS: Psychotic symptoms commonly occur after the discontinuation of high-dose steroid therapy; however, controlled tapering may prevent these side effects. Only a few cases have reported concomitant SARS-CoV-2 infection and manic episodes, often with an apparent relationship with steroid withdrawal syndrome. In this case, we considered psychotic vulnerability a condition that is often underestimated. In consideration of the SARS-CoV-2 pandemic, the case may represent an underlying trigger for psychotic decompensation, which, in concert with neuroinflammation, may induce a manic episode.

Risk factors associated with COVID-19 infection and mortality in nursing homes.

OBJECTIVE: The aim of this paper was to analyse the association of demographic, clinical and pharmacological risk factors with the presence of SARS-COV-2 virus infection, as well as to know the variables related to mortality from COVID-19 in nursing home (NH) residents. DESIGN: Retrospective case-control study. The study variables of those residents who acquired the infection (case) were compared with those of the residents who did not acquire it (control). A subgroup analysis was carried out to study those variables related to mortality. SITE: Nursing homes in the region of Guipúzcoa (Spain). PARTICIPANTS AND INTERVENTIONS: 4 NHs with outbreaks of SARS-CoV-2 between March and December 2020 participated in the study. The infectivity and, secondary, mortality was studied, as well as demographic, clinical and pharmacological variables associated with them. Data were collected from the computerised clinical records. MAIN MEASUREMENTS: Infection and mortality rate. Risk factors associated with infection and mortality. RESULTS: 436 residents were studied (median age 87 years (IQR 11)), 173 acquired SARS-CoV-2 (39.7%). People with dementia and Global Deterioration Scale ≥6 were less likely to be infected by SARS-CoV-2 virus [OR=0.65 (95% CI 0.43-0.97; p<.05)]. Overall case fatality rate was 10.3% (a mortality of 26% among those who acquired the infection). COVID-19 mortality was significantly associated with a Global Deterioration Scale ≥6 (OR=4.9 (95% CI 1.5-16.1)), COPD diagnosis (OR=7.8 (95% CI 1.9-31.3)) and antipsychotic use (OR=3.1 (95% CI 1.0-9.0)). CONCLUSIONS: Advanced dementia has been associated with less risk of SARS-CoV-2 infection but higher risk of COVID-19 mortality. COPD and chronic use of antipsychotics have also been associated with mortality. These results highlight the importance of determining the stage of diseases such as dementia as well as maintaining some caution in the use of some drugs such as antipsychotics.

"Please Don't Forget Us": A Descriptive Qualitative Study of Caregivers of Older Adults With Alzheimer's Disease and Related Dementias During the COVID-19 Pandemic.

The current descriptive qualitative study explored the perceived impact of the coronavirus disease 2019 pandemic on sleep disturbances and nighttime agitation; the reported use of antipsychotics and other sedating medications; and the overall well-being of older adults with Alzheimer's disease and related dementias (ADRD) and their caregivers. One investigator conducted in-depth, phone interviews with caregivers of nursing home residents with ADRD (four family caregivers [FCs], three nurse practitioners [NPs]) and seven FCs of older adults with ADRD who lived with them at home. Caregivers described multiple sleep disturbances. Nighttime agitation symptoms were perceived to continue or worsen, and sedating medications and nonpharmacological interventions were required. Adverse impacts on reported well-being were significant, and impacts were grouped into emotional, social, and physical themes. Caregivers said, "Please don't forget us," and requested telehealth support for those at home and technology and human resources for nursing homes to reduce adverse impacts. [Research in Gerontological Nursing, 15(5), 217-228.].

Effectiveness of electroconvulsive therapy in acute management of delirious mania in COVID-19 positive woman in second trimester pregnancy.

Delirious mania has been described as a state of acute excitement, fluctuating sensorium, affective and catatonic symptoms. Electroconvulsive therapy (ECT) despite being an effective treatment modality in such cases, has been under-utilised during pregnancy, mainly due to safety concerns. Here, we report the effectiveness of ECT in acute management of delirious mania in a 24 weeks pregnant woman who also tested COVID-19 positive during hospitalisation. Patient presented with three weeks history of acute manic excitement with period of altered sensorium and catatonic symptoms with no response to trials of two antipsychotic agents. After organic causes ruled out, patient was planned for ECT while ongoing antipsychotic was continued. After the first ECT session, patient tested positive for COVID-19, though asymptomatic and had to be shifted to COVID-19 isolation facility. Complete resolution of psychiatric symptoms occurred after fifth ECT. All five ECT sessions, including those in COVID-19 isolation facility were carried out under supervision of a multidisciplinary team. None of the ECT sessions had any major adverse event. Symptom remission sustained even following ECT discontinuation. No neonatal or maternal adverse effects observed after an uneventful delivery at 35 weeks. Both mother and child continued to maintain well in follow-up period of one year on oral olanzapine. In this unusual concurrent presentation of mania, delirium and catatonic symptoms during second trimester pregnancy, we highlighted the effectiveness and safety of ECT as a viable treatment modality. Additionally, management challenges posed by patient testing COVID-19 positive and then, administering ECT in COVID-19 isolation facility using personal protective equipment by multidisciplinary team has been highlighted.

Psychotropic Prescriptions During the COVID-19 Pandemic Among U.S. Children and Adolescents Receiving Mental Health Services.

Objective: Increased mental health problems among children and adolescents during the COVID-19 pandemic may have impacted psychotropic medication use. This study describes trends in monthly psychotropic medications before and early in the COVID-19 pandemic among 2- to 17-year-old children and adolescents with mental health disorders. Methods: A cross-sectional study design using the 2019-2020 IQVIA™ prescription and medical commercial claims data to estimate the proportion of children and adolescents with any psychotropic prescription in the month out of all with any mental health-related medical or prescription services in the month and the year-over-year percent change. We assessed monthly proportions of youth who filled a psychotropic prescription overall and by psychotropic class, stratified by age and gender. Results: Of the 8,896,713 children and adolescents in the sample, 24.7% received psychotropic medication during the study period. The proportion of the cohort prescribed a psychotropic medication in a given month averaged 27%-28% from January 2019 to February 2020, peaked at 36.9% in April 2020, and gradually declined to 28.7% in September 2020. The largest year-over-year percent change was in April for antipsychotic (41.9%) and antidepressant (37.9%) medication, which remained higher in September 2020 compared to September 2019, particularly among ages 6 years or older and females. Conclusion: The proportion of youth with a psychotropic prescription increased at the onset of the COVID-19 pandemic, later returning to prepandemic levels. However, antipsychotics and antidepressants remained higher than prepandemic, highlighting the need to further understand the long-lasting effects of the pandemic on children and adolescents.

Incidence and Outcomes of SARS-CoV-2 Infection in Older Adults Living with Dementia: A Population-Based Cohort Study.

BACKGROUND: The identification of risk factors for SARS-CoV-2 infection and mortality in patients with dementia is a key aspect to support clinical decisions and public health interventions. OBJECTIVE: To assess the incidence of SARS-CoV-2 infection and COVID-19 related death in a cohort of patients with dementia residing in the Lazio region and to investigate predicting factors for both infection and mortality. METHODS: This population-based study used information from administrative databases and the SARS-CoV-2 infection surveillance system. Patients with dementia (age ≥65) were enrolled as of December 31, 2019 and followed-up until February 28, 2021. Cumulative risk of infection and death within 60 days of infection onset, and age-standardized incidence (SIR) and mortality (SMR) ratios were calculated. Logistic regression models were applied to identify factors associated with infection and mortality. RESULTS: Among 37,729 dementia patients, 2,548 had a diagnosis of SARS-CoV-2 infection. The crude risk of infection was 6.7%. An increase in risk of infection was observed both in women (SIR 1.72; 95% CI 1.64-1.80) and men (SIR 1.43; 95% CI 1.33-1.54). Pneumonia, cerebrovascular and blood diseases, femur fracture, anxiety, antipsychotic and antithrombotic use were associated with an increased risk of infection. The crude risk of death was 31.0%, the SMRs 2.32 (95% CI 2.05-2.65) for men, and 2.82 (95% CI 2.55-3.11) for women. Factors associated with mortality included: male gender, age ≥85, symptoms at the diagnosis, antipsychotic and systemic antibiotics treatment. CONCLUSION: These findings emphasize the need of close and tailored monitoring of dementia patients to reduce the impact of COVID-19 on this fragile population.

An Updated Analysis of Psychotropic Medicine Utilisation in Older People in New Zealand from 2005 to 2019.

BACKGROUND: Psychotropic medicine utilisation in older adults continues to be of interest because of overuse and concerns surrounding its safety and efficacy. OBJECTIVE: This study aimed to characterise the utilisation of psychotropic medicines in older people in New Zealand. METHODS: We conducted a repeated cross-sectional analysis of national dispensing data from 1 January, 2005 to 31 December, 2019. We defined utilisation using the Anatomical Therapeutic Chemical classification defined daily dose system. Utilisation was measured in terms of the defined daily dose (DDD) per 1000 older people per day (TOPD). RESULTS: Overall, the utilisation of psychotropic medicines increased marginally by 0.42% between 2005 and 2019. The utilisation increased for antidepressants (72.42 to 75.21 DDD/TOPD) and antipsychotics (6.06-19.04 DDD/TOPD). In contrast, the utilisation of hypnotics and sedatives (53.74-38.90 DDD/TOPD) and anxiolytics decreased (10.20-9.87 DDD/TOPD). The utilisation of atypical antipsychotics increased (4.06-18.72 DDD/TOPD), with the highest percentage change in DDD/TOPD contributed by olanzapine (520.6 %). In comparison, utilisation of typical antipsychotics was relatively stable (2.00-2.06 DDD/TOPD). The utilisation of venlafaxine increased remarkably by 5.7 times between 2005 and 2019. The utilisation of zopiclone was far greater than that of other hypnotics in 2019. CONCLUSIONS: There was only a marginal increase in psychotropic medicines utilisation from 2005 to 2019 in older adults in New Zealand. There was a five-fold increase in the utilisation of antipsychotic medicines. Continued monitoring of psychotropic medicine utilisation will be of interest to understand the utilisation of antidepressants and antipsychotic medicines during the coronavirus disease 2019 pandemic year.

Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review.

BACKGROUND: Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia. Despite its therapeutic benefits, it is still widely underused, mainly because of its potential to cause agranulocytosis and neutropenia. Prescribing clozapine in COVID-19-positive patients became more challenging because of this potential side effect. This article is a review of literature on the risk of neutropenia associated with clozapine treatment in patients with COVID-19. AREAS OF UNCERTAINTY: In clozapine-treated COVID-19-positive patients, neutropenia was reported in some cases; is it a consequence of clozapine treatment or of SARS-Co2 infection? DATA SOURCES: Data were extracted from 2 databases: PubMed/MEDLINE and Google Scholar. We selected all original reports, from March 2020 until May 2022, on neutropenia associated with clozapine treatment in positive COVID-19 patients. Eleven studies were selected for the final analysis. THERAPEUTIC ADVANCES: Before the COVID-19 pandemic, neutropenia in clozapine-treated patients was reported in 3.8% of cases. During the pandemic, neutropenia rates seemed to be higher. As per the cause of neutropenia, studies reported contradictory results. We aim to clarify rates and causes of neutropenia in clozapine-treated COVID-19-positive patients. RESULTS: Three hundred eighty-eight articles were initially selected from the 2 databases. After excluding duplicates, unrelated articles, reviews, and guidelines, 11 studies were analyzed, all centered on clozapine treatment, COVID-19 infection, and associated neutropenia. CONCLUSIONS: Clozapine treatment in COVID-19-positive patients may be associated with a transient reduction of absolute neutrophils count, in some cases reaching neutropenia levels. Neutropenia rates reported in SARS-CoV-2-infected patients are higher than the prepandemic reports; therefore, we assume that the cause might be a result of the immunological interference between clozapine and SARS-CoV-2. Clozapine treatment needs to be continued whenever possible, with dose adjustments in relation to blood test results.

Psychotropic Drug Prescription in Nursing Homes During the COVID-19 Pandemic.

BACKGROUND: To limit the introduction of coronavirus disease 2019 (COVID-19) into nursing homes, restrictive measures and social distancing were implemented; however, these caused an increase in affective disorders such as depression and anxiety and an alteration of the behavioral and psychological symptoms of dementia. Therefore, it is expected that prescription trends of psychotropic drugs in nursing homes during the pandemic may have changed significantly. OBJECTIVE: This study aims to compare patterns of prescribing psychotropic drugs in nursing homes during the COVID-19 pandemic to those of the pre-pandemic period. METHODS: This cross-sectional multicenter study was conducted in geriatric units and psychogeriatric units in seven nursing homes in Gipuzkoa, Spain. On 1 March, 2020, data regarding 511 residents in geriatric units and 163 in psychogeriatric units were recorded. This study examined utilization percentages for psychotropic drugs before the pandemic (April 2018-March 2020) and during the pandemic (April 2020-March 2021) in light of projected usage based on previous years. Following the Anatomical, Therapeutic, Chemical Classification System, four therapeutic groups were analyzed: antipsychotics (N05A), benzodiazepines (N05B and N05C), antidepressants (N06A), and antiepileptic drugs (N03A). RESULTS: In the case of geriatric units, a downward trend of prescription was reversed for antipsychotics (-0.41; 95% confidence interval [CI] -1.41, 0.60). Benzodiazepine use also decreased less than expected (-2.00; 95% CI -3.00, -1.00). Antidepressant use increased more than predicted (0.02; 95% CI -0.97, 1.01), as did antiepileptic drug use (2.93; 95% CI 2.27, 3.60). In the psychogeriatric units, the drop in antipsychotic utilization was less than expected (-2.31; 95% CI -3.68, -0.93). Although it was expected that the prescription of benzodiazepines would decrease, usage remained roughly the same (-0.28; 95% CI -2.40, 2.34). Utilization of antidepressants (8.57; 95% CI 6.89, 10.24) and antiepileptic drugs (6.10; 95% CI 3.20, 9.00) increased significantly, which was expected, based on the forecast. CONCLUSIONS: For all categories, usage of psychotropic drugs was higher than anticipated based on the forecast; this increase might be related to the worsening of emotional and behavioral disorders caused by the restrictive measures of the COVID-19 pandemic.