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.

[Mental disorders associated with acute COVID-19: clinical picture, therapy approaches]. / Psikhicheskie rasstroistva, assotsiirovannye s ostroi fazoi techeniya COVID-19: klinika, podkhody k terapii.

BACKGROUND: The purpose is to study the structure of clinical manifestations of mental disorders in the acute period of COVID-19 among patients, who were hospitalized with a new coronavirus infection and their relations with the severity of the immune response, to assess the efficacy and safety profile of the spectrum of used psychopharmacotherapy. MATERIAL AND METHODS: A study was conducted of patients, hospitalized to the department of infectious diseases and repurposed for COVID-19 clinical departments with a diagnosis of COVID-19 (compliance with the criteria for ICD-10: U07.1) from September 2020 to March 2021. Study design: single center opened retrospective cohort study. The main group is consisted of 72 patients, average age - 71 [56.0; 81.0] years, the part of women - 64.0%. The control group (n=2221) was formed from those hospitalized in the same period with a diagnosis of U07.1 without mental disorders during the hospitalization period, average age 62 [51.0; 72.0] years, the part of women - 48.7%. Mental disorders were diagnosed in accordance to ICD-10 criteria, the following peripheral markers of inflammation, that were evaluated: neutrophils, lymphocytes, platelets, ESR, C-reactive protein, interleukin; also coagulogram indicators: APTT, fibrinogen, prothrombin time, D-dimers. RESULTS: In the following range of mental disorders were identified: a depressive episode (ICD-10 F32) by 31 patients, by 22 - a disorder of adaptive reactions (ICD-10 F43.2), by 5 - delirium not caused by alcohol or other psychoactive substances (ICD-10 F05), by 14 - mild cognitive impairment caused by damage and disfunction of the brain or somatic diseases (ICD-10 F06.7). In comparison with the control group, these patients showed a statistically significant (p<0.001) increasing the level of inflammatory markers (CRP, IL-6) and changes in the coagulogram. and anxiolytic drugs were used most often. Regarding psychopharmacotherapy, drugs from the group of atypical antipsychotics - quetiapine was prescribed in 44% patients in average dose 62.5 mg per day, and Melatonin receptor type 1 and 2 agonist and antagonists of serotonin 5-HT2C receptors: agomelatine was prescribed in 11% patients in average dose 25 mg per gay. CONCLUSION: The results of the study confirm the heterogeneity of the structure of mental disorders in the acute form of coronavirus infection, revealing the relations between the clinical picture and laboratory parameters of the immune response to systemic inflammation. Recommendations are given for the choice of psychopharmacotherapy, in conformity with the peculiarities of pharmacokinetics and interaction with somatotropic therapy.

Systematic review of community pharmacist administration of long-acting injectable antipsychotic medications.

BACKGROUND: Long-acting injectable antipsychotic (LAIA) medications offer an effective treatment option for patients with serious mental illness. Despite demonstrated clinical safety and efficacy as well as increased adherence and less frequent administration compared with daily oral regimens, LAIAs remain underutilized in clinical practice. With legislation allowing pharmacists to administer injectable medications in 48 U.S. states, community pharmacies are uniquely positioned to serve as an access point for patients with serious mental illnesses to receive LAIA injections. OBJECTIVE: This study aimed to conduct a systematic review of the health and economic benefits and costs of community pharmacist administration of LAIA medications. METHODS: A systematic search of the literature published from January 1996 to April 2022 was conducted across 3 databases (Embase, PubMed, and Scopus Plus). Publications describing pharmacist administration of LAIA medications in outpatient settings were included. Publications that examined the use of LAIAs but did not involve a pharmacist administering the medication were excluded. RESULTS: Of 2261 publications reviewed, we identified 8 publications (4 articles and 4 abstracts) that met our inclusion criteria, of which only 7 included results. Four studies reported high medication adherence achieved by patients receiving pharmacist-administered LAIAs. Two publications surveyed patient satisfaction with pharmacist administration of LAIAs in community pharmacy settings. One study found pharmacists' mixed attitudes regarding LAIA administration and time and safety barriers to offering the service. CONCLUSION: We found very little evidence on the impact of pharmacist administration of LAIAs on patient outcomes. This review highlights the need to generate greater evidence on the health and economic benefits as well as financial models for pharmacists to administer LAIA medications in outpatient and community pharmacy settings. Such evidence could support more community pharmacists to offer LAIA medications and contribute to the shift toward value-based care.

"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.].

Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom.

PURPOSE/BACKGROUND: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. METHODS: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. FINDINGS/RESULTS: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. IMPLICATIONS/CONCLUSIONS: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.

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.

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.