Adherence to Psychotropic Medication Before and During COVID-19: A Population-Wide Retrospective Observational Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic and associated public health measures have shifted the way people access health care. We aimed to study the effects of the COVID-19 pandemic on psychotropic medication adherence. METHODS: A retrospective cohort study using administrative data from the Manitoba Centre for Health Policy Manitoba Population Research Data Repository was conducted. Outpatients who received at least 1 prescription for an antidepressant, antipsychotic, anxiolytic/sedative-hypnotic, cannabinoid, lithium, or stimulants from 2015 to 2020 in Manitoba, Canada, were included. Adherence was measured using the proportion of individuals with a mean possession ratio of ≥0.8 over each quarter. Each quarter of 2020 after COVID-19-related health measures were implemented was compared with the expected trend using autoregression models for time series data plus indicator variables. Odds ratio of drug discontinuation among those previously adherent in 2020 was compared with each respective quarter of 2019. RESULTS: There were 1,394,885 individuals in the study population in the first quarter of 2020 (mean [SD] age, 38.9 [23.4] years; 50.3% female), with 36.1% having a psychiatric diagnosis in the preceding 5 years. Compared with the expected trend, increases in the proportions of individuals adherent to antidepressants and stimulants were observed in the fourth quarter (October-December) of 2020 (both P < 0.001). Increases in the proportions of individuals with anxiolytic and cannabinoid adherence were observed in the third quarter (July-September) of 2020 (both P < 0.05), whereas a decrease was seen with stimulants in the same quarter ( P < 0.0001). No significant changes were observed for antipsychotics. All drug classes except lithium had decreases in drug discontinuation in previously adherent patients during the pandemic compared with 2019. CONCLUSIONS: Improved adherence to most psychotropic medications in the 9 months after public health restrictions were enacted was observed. Patients who were already adherent to their psychotropic medications were less likely to discontinue them during the pandemic.

A case of schizophrenia with relapsed catatonia successfully treated with blonanserin transdermal patch.

BACKGROUND: Catatonia is a syndrome that may present with stupor, immobility, and postural retention, and appears in various primary disorders including schizophrenia, depressive disorders, and neurodevelopmental disorders. CASE PRESENTATION: In this report, we describe a 34-year-old female patient with schizophrenia, who had previously been treated with antipsychotic agents to improve psychotic symptoms with delusional symptoms and catatonia. However, she relapsed with catatonic symptoms around 1 year after she voluntarily discontinued the prescribed antipsychotic medications by herself. Her catatonia was successfully improved using the transdermal blonanserin patch, a drug formulation globally first approved in Japan in 2019. DISCUSSION: Although benzodiazepines or electroconvulsive therapy have been recommended as the first-line treatment of catatonic manifestation observed in psychiatric patients, this patient responded well to antipsychotic blonanserin. From the differential drug responses, catatonia may be the complex of heterogeneous conditions with different pathophysiologies.

Psychotic Disorders in the Elderly: Diagnosis, Epidemiology, and Treatment.

This review covers the latest advances in our understanding of psychosis in the elderly population with respect to diagnosis, epidemiology, and treatment. Major topics of discussion include late life psychiatric disorders such as schizophrenia, schizoaffective disorder, and delusional disorder as well as dementia-related psychosis. Clinical differences between early-onset and late-onset disorders are reviewed in terms of prevalence, symptomatology, and approach to treatment. Newly revised research and clinical criteria for dementia-related psychosis are referenced. The evidence base for emerging therapies including citalopram and pimavanserin in relation to conventional therapies such as atypical antipsychotics are discussed..

Psychotic Symptoms After SARS-CoV-2 Infection.

ABSTRACT: This case series reports three middle-aged male patients with no prior history of psychiatric disorders who developed psychotic symptoms with manic characteristics after COVID-19 infection. They presented mystic and paranoid delusions associated with euphoria, logorrheic, insomnia, and bizarre behaviors. Two of them required psychiatric hospitalization and one received corticosteroids. Treatment with antipsychotic medication improved their symptoms in a few weeks. This case series reports the new-onset psychosis probably due to COVID-19 infection. Pathogenetic speculation about the probable causes of COVID-19 psychosis, such as inflammatory reaction and corticosteroid use, was done. Moreover, other probable causes of manic psychosis, such as late-onset bipolar disorder, were also considered and ruled out. There is a need for more research to determine the causality between psychotic symptoms and COVID-19 infection.

Lessons from the coronavirus disease 2019 pandemic in schizophrenia: a review.

PURPOSE OF REVIEW: Multiple countries have reported increased COVID-19 mortality in patients with schizophrenia. The purpose of this review was to synthetize the consequences of the pandemic on patients with schizophrenia including vaccination data. RECENT FINDINGS: We have synthetized data on the increased risk of infection and increased mortality, the impact of the pandemic and lockdowns on psychiatric care, vaccination policies, unwillingness to vaccine in patients and the rates of vaccination. SUMMARY: Schizophrenia has been confirmed at increased risk of both COVID-19 infection and developing a severe/lethal form of the infection. Patients with schizophrenia should, therefore, be prioritized for vaccination whenever possible and should be prioritized for psychiatric and somatic care access. Psychotic symptomatology may be a barrier to vaccination in some patients, and heterogenous vaccination rates were identified in national databases. The COVID-19 pandemic has been also a unique opportunity to develop telehealth. A mixed face-to-face and distance model should be encouraged, whenever possible, to improve the experience of patients, relatives and healthcare professionals. No major change of long-acting antipsychotics has been reported in most countries, and there was no consistent evidence for clozapine prescription to increase the risk of COVID-19 infection or severe outcomes.

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.

Antipsychotic Augmentation With N-Acetylcysteine for Patients With Schizophrenia.

N-acetylcysteine (NAC) augmentation of antipsychotic medication is one of very many antipsychotic augmentation strategies that have been studied in schizophrenia. A recent systematic review and meta-analysis of 6 randomized controlled trials (RCTs) found that NAC (median dose, 2,000 mg/d) improved several clinical outcomes at different time points with medium to large effect sizes; however, many of the significant findings in this meta-analysis are suspect because they appeared to be influenced by 2 short-term (8-week) RCTs with outlying characteristics. Important findings not influenced by the 2 outlying RCTs were significant attenuation by NAC of negative symptom (3 RCTs) and total psychopathology (2 RCTs) ratings at ≥ 24 weeks and improvement in working memory but not processing speed (3 RCTs). Of these findings, reduction in psychopathology ratings, though statistically significant, appeared too small to be clinically meaningful. Finally, a newly published, moderately large RCT of NAC (2,000 mg/d) in schizophrenia patients refractory to clozapine found that 1 year of treatment with NAC did not outperform placebo for any clinical, cognitive, or quality of life outcome. The take-home message is that it is premature to recommend the use of NAC to treat schizophrenia for any target domain in routine clinical practice and that there does not appear to be a role for NAC for any indication in clozapine-refractory schizophrenia. However, it may be worth studying whether NAC, dosed at 2,000 mg/d or higher for 6 months or longer, improves functional outcomes in schizophrenia.

Agitation in schizophrenia: origins and evidence-based treatment.

PURPOSE OF REVIEW: Agitation associated with schizophrenia remains an important clinical concern and if not managed effectively, can escalate into aggressive behavior. This is a review of the recent biomedical literature on agitation in individuals with schizophrenia. RECENT FINDINGS: Themes in the recent literature include consideration of comorbidities such as cigarette smoking and cannabis use. Surveys reveal that pharmacological approaches to manage agitation have changed little, with haloperidol remaining in common use and intramuscular administration of antipsychotics and/or benzodiazepines being frequently administered to more severely agitated/aggressive individuals. Of note, ketamine has been recently adopted for use in severe agitation in medical emergency departments, but the risk of this medication for people with schizophrenia is unclear. At present, inhaled loxapine remains the only rapidly acting noninjectable FDA-approved treatment for agitation associated with schizophrenia. In development is an intranasal formulation for olanzapine (a well characterized atypical antipsychotic already approved to treat agitation) and a sublingual film for dexmedetomidine (an α2-adrenergic agonist used as an anesthetic and now being repurposed). SUMMARY: Comorbidities can contribute to agitation and can make an accurate differential diagnosis challenging. The ongoing development of rapidly acting novel formulations of antiagitation medications, if successful, may facilitate clinical treatment by providing additional options.

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.

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.

Actionable Predictive Factors of Homelessness in a Psychiatric Population: Results from the REHABase Cohort Using a Machine Learning Approach.

BACKGROUND: There is a lack of knowledge regarding the actionable key predictive factors of homelessness in psychiatric populations. Therefore, we used a machine learning model to explore the REHABase database (for rehabilitation database-n = 3416), which is a cohort of users referred to French psychosocial rehabilitation centers in France. METHODS: First, we analyzed whether the different risk factors previously associated with homelessness in mental health were also significant risk factors in the REHABase. In the second step, we used unbiased classification and regression trees to determine the key predictors of homelessness. Post hoc analyses were performed to examine the importance of the predictors and to explore the impact of cognitive factors among the participants. RESULTS: &nbsp;First, risk factors that were previously found to be associated with homelessness were also significant risk factors in the REHABase. Among all the variables studied with a machine learning approach, the most robust variable in terms of predictive value was the nature of the psychotropic medication (sex/sex relative mean predictor importance: 22.8, σ = 3.4). Post hoc analyses revealed that first-generation antipsychotics (15.61%; p < 0.05 FDR corrected), loxapine (16.57%; p < 0.05 FWER corrected) and hypnotics (17.56%; p < 0.05 FWER corrected) were significantly associated with homelessness. Antidepressant medication was associated with a protective effect against housing deprivation (9.21%; p < 0.05 FWER corrected). CONCLUSIONS: Psychotropic medication was found to be an important predictor of homelessness in our REHABase cohort, particularly loxapine and hypnotics. On the other hand, the putative protective effect of antidepressants confirms the need for systematic screening of depression and anxiety in the homeless population.

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.