[Pharmacological trials evaluating treatment options for neuropsychiatric symptoms in post-COVID. A narrative review]. / Essais pharmacologiques sur les traitements des symptômes neuropsychiatriques du post-Covid. Revue narrative de la littérature.

Post-COVID prevalence's is estimated at 10 % in the general population. The neuropsychiatric symptoms, which are frequent (up to 30 %), can severely affect the quality of life of patients affected by this condition, notably by significantly reducing their working ability. To date, no pharmacologic treatment is available for post-COVID, apart from symptomatic treatments. A large number of pharmacological clinical trials for post-COVID are underway since 2021. A number of these trials targets neuropsychiatric symptoms, based on the various underlying pathophysiological hypotheses. The objective of this narrative review is to provide an overview of these ongoing trials targeting neuropsychiatric symptoms in post-COVID.

La prévalence du syndrome post-Covid est évaluée à 10 % dans la population générale. Les symptômes neuropsychiatriques, fréquents (jusqu'à 30 %), peuvent sévèrement affecter la qualité de vie des patients qui en sont atteints et, notamment, en réduisant significativement leur capacité de travail. À ce jour, il n'existe pas de traitement médicamenteux pour le syndrome post-Covid, en dehors des traitements symptomatiques. C'est pourquoi, un grand nombre d'essais thérapeutiques concernant le post-Covid sont en cours depuis 2021. Un certain nombre d'entre eux ciblent les symptômes neuropsychiatriques en se basant sur les diverses hypothèses physiopathologiques élaborées sur le post-Covid. L'objectif de cette revue narrative est d'établir un état des lieux des essais thérapeutiques en cours ciblant les symptômes neuropsychiatriques du post-Covid.

COVID-19 and catatonia: Prevalence, challenges, pathophysiology, and treatment.

BACKGROUND: Emerging literature supports the association between acute COVID-19 infection and neuropsychiatric complications. This article reviews the evidence for catatonia as a potential neuropsychiatric sequela of COVID-19 infection. METHODS: PubMed was searched using the terms catatonia, severe acute respiratory syndrome coronavirus 2, and COVID-19. Articles were limited to those published in the English language between 2020 and 2022. Forty-five articles that specifically studied catatonia associated with acute COVID-19 infection were screened. RESULTS: Overall, 30% of patients with severe COVID-19 infection developed psychiatric symptoms. We found 41 cases of COVID-19 and catatonia, with clinical presentations that varied in onset, duration, and severity. One death was reported in a case of catatonia. Cases were reported in patients with and without a known psychiatric history. Lorazepam was successfully used, along with electroconvulsive therapy, antipsychotics, and other treatments. CONCLUSIONS: Greater recognition and treatment of catatonia in individuals with COVID-19 infection is warranted. Clinicians should be familiar with recognizing catatonia as a potential outcome of COVID-19 infection. Early detection and appropriate treatment are likely to lead to better outcomes.

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.

Ancient Roots of Today's Emerging Renaissance in Psychedelic Medicine.

An international ban on psychedelics initiated by the United Nations' Convention on Psychotropic Substances in 1971 restricted the clinical use of these ancient psychoactive substances. Yet, in an era marked by rising mental health concerns and a growing "Deaths of Despair" epidemic (i.e., excess mortality and morbidity from suicide, drug overdose, and alcoholism), the structured psychedelic use that has long been a part of ritual healing experiences for human societies is slowly regaining credibility in Western medicine for its potential to treat various mental health conditions. We use a historical lens to examine the use of psychedelic therapies over time, translate ancient lessons to contemporary clinical and research practice, and interrogate the practical and ethical questions researchers must grapple with before they can enter mainstream medicine. Given the COVID-19 pandemic and its contributions to the global mental health burden, we also reflect on how psychedelic therapy might serve as a tool for medicine in the aftermath of collective trauma. Ultimately, it is argued that a "psychedelic renaissance" anchored in the lessons of antiquity can potentially help shift healthcare systems-and perhaps the broader society-towards practices that are more humane, attentive to underlying causes of distress, and supportive of human flourishing.

Psychotropic Medication Use and Psychiatric Disorders During the COVID-19 Pandemic Among Danish Children, Adolescents, and Young Adults.

Importance: The direct and indirect implications of the COVID-19 pandemic have been associated with the mental health of children and adolescents, but it is uncertain whether these implications have been associated with changes in prescribing and diagnosis patterns. Objective: To examine psychotropic medication use and rates of psychiatric disorders in Danish children, adolescents, and young adults during the COVID-19 pandemic. Design, Setting, and Participants: This population-based, descriptive register-based cohort study included all Danish individuals aged 5 to 24 years from January 1, 2017, until June 30, 2022. Main Outcomes and Measures: Rates of filled prescriptions of psychotropic medications, including antipsychotics, anxiolytics, hypnotics, sedatives, antidepressants, and psychostimulants, and all inpatient and outpatient contacts with mental and behavioral disorders. Rates of new (incident) and total (prevalent) psychotropic medication use and psychiatric diagnoses were estimated. Rate ratios (RRs) were assessed between observed and expected numbers of incident psychotropic medication use or psychiatric diagnoses from March 2020 to June 30, 2022, comparing observed numbers with expected numbers predicted from the modeled prepandemic trend. Results: The study identified 108 840 (58 856 female individuals [54%]; median [IQR] age, 18 [14-22] years) incident psychotropic medication users. From March 2020 (first national lockdown) to June 2022, the rate of incident users of any psychotropic medication showed a relative increase of 18% (RR, 1.18; CI, 1.17-1.20) compared with expected numbers, which was primarily associated with an increase among those aged 12 to 17 years of 37% (RR, 1.37; 95% CI, 1.34-1.41). Similarly, there was an overall relative increase of incident psychiatric disorders of 5% (incidence rate, 1.05; CI, 1.04-1.07) (incident cases, 114 048 [58 708 female individuals (51%)]), which was associated with an increase in hyperkinetic disorders (RR, 1.13; CI, 1.09-1.18) and anxiety disorders (RR, 1.04; CI, 1.02-1.06). Prevalence patterns showed similar trends of an overall increase in psychotropic medication use and psychiatric disorders. One of 3 new users of an individual drug group had filled a prescription for a drug from another psychotropic medication group within the prior 6 months. Conclusions and Relevance: The results of this cohort study suggest that Danish youths experienced an increase in rates of psychotropic treatment and psychiatric disorder diagnoses during the COVID-19 pandemic, which was most pronounced among those aged 12 to 17 years. The increase was observed for children and adolescents with and without a psychiatric history within the last 5 years.

Oxytocin: An Old Hormone, a Novel Psychotropic Drug and its Possible Use in Treating Psychiatric Disorders.

BACKGROUND: Oxytocin is a nonapeptide synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Historically, this molecule has been involved as a key factor in the formation of infant attachment, maternal behavior and pair bonding and, more generally, in linking social signals with cognition, behaviors and reward. In the last decades, the whole oxytocin system has gained a growing interest as it was proposed to be implicated in etiopathogenesis of several neurodevelopmental and neuropsychiatric disorders. METHODS: With the main goal of an in-depth understanding of the oxytocin role in the regulation of different functions and complex behaviors as well as its intriguing implications in different neuropsychiatric disorders, we performed a critical review of the current state of the art. We carried out this work through the PubMed database up to June 2021 with the search terms: 1) "oxytocin and neuropsychiatric disorders"; 2) "oxytocin and neurodevelopmental disorders"; 3) "oxytocin and anorexia"; 4) "oxytocin and eating disorders"; 5) "oxytocin and obsessive- compulsive disorder"; 6) "oxytocin and schizophrenia"; 7) "oxytocin and depression"; 8) "oxytocin and bipolar disorder"; 9) "oxytocin and psychosis"; 10) "oxytocin and anxiety"; 11) "oxytocin and personality disorder"; 12) "oxytocin and PTSD". RESULTS: Biological, genetic, and epigenetic studies highlighted quality and quantity modifications in the expression of oxytocin peptide or in oxytocin receptor isoforms. These alterations would seem to be correlated with a higher risk of presenting several neuropsychiatric disorders belonging to different psychopathological spectra. Collaterally, the exogenous oxytocin administration has shown to ameliorate many neuropsychiatric clinical conditions. CONCLUSION: Finally, we briefly analyzed the potential pharmacological use of oxytocin in a patient with severe symptomatic SARS-CoV-2 infection due to its anti-inflammatory, antioxidative and immunoregulatory properties.

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.

Using the Intranasal Route to Administer Drugs to Treat Neurological and Psychiatric Illnesses: Rationale, Successes, and Future Needs.

While the intranasal administration of drugs to the brain has been gaining both research attention and regulatory success over the past several years, key fundamental and translational challenges remain to fully leveraging the promise of this drug delivery pathway for improving the treatment of various neurological and psychiatric illnesses. In response, this review highlights the current state of understanding of the nose-to-brain drug delivery pathway and how both biological and clinical barriers to drug transport using the pathway can been addressed, as illustrated by demonstrations of how currently approved intranasal sprays leverage these pathways to enable the design of successful therapies. Moving forward, aiming to better exploit the understanding of this fundamental pathway, we also outline the development of nanoparticle systems that show improvement in delivering approved drugs to the brain and how engineered nanoparticle formulations could aid in breakthroughs in terms of delivering emerging drugs and therapeutics while avoiding systemic adverse effects.

Association Between the Use of Psychotropic Medications and the Risk of COVID-19 Infection Among Long-term Inpatients With Serious Mental Illness in a New York State-wide Psychiatric Hospital System.

Importance: Individuals with serious mental illness are at increased risk of severe COVID-19 infection. Several psychotropic medications have been identified as potential therapeutic agents to prevent or treat COVID-19 but have not been systematically examined in this population. Objective: To evaluate the associations between the use of psychotropic medications and the risk of COVID-19 infection among adults with serious mental illness receiving long-term inpatient psychiatric treatment. Design, Setting, and Participants: This retrospective cohort study assessed adults with serious mental illness hospitalized in a statewide psychiatric hospital system in New York between March 8 and July 1, 2020. The final date of follow-up was December 1, 2020. The study included 1958 consecutive adult inpatients with serious mental illness (affective or nonaffective psychoses) who received testing for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction or antinucleocapsid antibodies and were continuously hospitalized from March 8 until medical discharge or July 1, 2020. Exposures: Psychotropic medications prescribed prior to COVID-19 testing. Main Outcomes and Measures: COVID-19 infection was the primary outcome, defined by a positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction or antibody test result. The secondary outcome was COVID-19-related death among patients with laboratory-confirmed infection. Results: Of the 2087 adult inpatients with serious mental illness continuously hospitalized during the study period, 1958 (93.8%) underwent testing and were included in the study; 1442 (73.6%) were men, and the mean (SD) age was 51.4 (14.3) years. A total of 969 patients (49.5%) had laboratory-confirmed COVID-19 infection that occurred while they were hospitalized; of those, 38 (3.9%) died. The use of second-generation antipsychotic medications, as a class, was associated with decreased odds of infection (odds ratio [OR], 0.62; 95% CI, 0.45-0.86), whereas the use of mood stabilizers was associated with increased odds of infection (OR, 1.23; 95% CI, 1.03-1.47). In a multivariable model of individual medications, the use of paliperidone was associated with decreased odds of infection (OR, 0.59; 95% CI, 0.41-0.84), and the use of valproic acid was associated with increased odds of infection (OR, 1.39; 95% CI, 1.10-1.76). Clozapine use was associated with reduced odds of mortality in unadjusted analyses (unadjusted OR, 0.25; 95% CI, 0.10-0.62; fully adjusted OR, 0.43; 95% CI, 0.17-1.12). Conclusions and Relevance: In this cohort study of adults hospitalized with serious mental illness, the use of second-generation antipsychotic medications was associated with decreased risk of COVID-19 infection, whereas the use of valproic acid was associated with increased risk. Further research is needed to assess the mechanisms that underlie these findings.

Impact of COVID-19 on mental health in a Low and Middle-Income Country.

Mental disorders (MD) are commonly comorbid with cardiovascular, metabolic, and some infectious diseases. Since the current SARS-CoV-2 epidemic is affecting the most multimorbid individuals, we might expect that the epidemic will be particularly problematic for people with MD. Understanding the burden of an outbreak on mental health is fundamental to effective action towards containing the spread of the disease, as psychopathology might reduce endurance during the lockdown. This can potentially reduce adhesion to ongoing treatment resulting in avoidable recurrence of a disorder. Additionally, there is the stress caused by the eminent risk of infection or economic uncertainty, especially in low-middle income settings. This is an overview on the expected influence of the COVID-19 on mental health from a research group that has not long ago been involved in the Zika epidemic. It aims to discuss the effects of the pandemic on a Low and Middle-Income country (LMIC), Brazil.

Association between FIASMA psychotropic medications and reduced risk of intubation or death in individuals with psychiatric disorders hospitalized for severe COVID-19: an observational multicenter study.

The acid sphingomyelinase (ASM)/ceramide system may provide a useful framework for better understanding SARS-CoV-2 infection and the repurposing of psychotropic medications functionally inhibiting the acid sphingomyelinase/ceramide system (named FIASMA psychotropic medications) against COVID-19. We examined the potential usefulness of FIASMA psychotropic medications in patients with psychiatric disorders hospitalized for severe COVID-19, in an observational multicenter study conducted at Greater Paris University hospitals. Of 545 adult inpatients, 164 (30.1%) received a FIASMA psychotropic medication upon hospital admission for COVID-19. We compared the composite endpoint of intubation or death between patients who received a psychotropic FIASMA medication at baseline and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, psychiatric and other medical comorbidity, and other medications. FIASMA psychotropic medication use at baseline was significantly associated with reduced risk of intubation or death in both crude (HR = 0.42; 95%CI = 0.31-0.57; p < 0.01) and primary inverse probability weighting (IPW) (HR = 0.50; 95%CI = 0.37-0.67; p < 0.01) analyses. This association was not specific to one FIASMA psychotropic class or medication. Patients taking a FIASMA antidepressant at baseline had a significantly reduced risk of intubation or death compared with those taking a non-FIASMA antidepressant at baseline in both crude (HR = 0.57; 95%CI = 0.38-0.86; p < 0.01) and primary IPW (HR = 0.57; 95%CI = 0.37-0.87; p < 0.01) analyses. These associations remained significant in multiple sensitivity analyses. Our results show the potential importance of the ASM/ceramide system framework in COVID-19 and support the continuation of FIASMA psychotropic medications in these patients and the need of large- scale clinical trials evaluating FIASMA medications, and particularly FIASMA antidepressants, against COVID-19.

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.

Mortality in association with antipsychotic medication use and clinical outcomes among geriatric psychiatry outpatients with COVID-19.

OBJECTIVES: Older adults are particularly vulnerable to the negative consequences of antipsychotic exposure and are disproportionally affected by higher mortality from coronavirus disease 2019 (COVID-19). Our goal was to determine whether concurrent antipsychotic medication use was associated with increased COVID-19 mortality in older patients with preexisting behavioral health problems. We also report on findings from post-COVID follow-ups. DESIGN: Retrospective observational study. PARTICIPANTS: Outpatients at a geriatric psychiatric clinic in New York City. MEASUREMENTS: Demographic and clinical data including medication, diagnosis and Clinical Global Impression Severity (CGI-S) scales on outpatients who had COVID-19 between February 28th and October 1st 2020 were extracted from the electronic health records (EHR) from the hospital. RESULTS: A total of 56 patients were diagnosed with COVID-19 (mean age 76 years; median age 75 years) and 13 (23.2%) died. We found an increased mortality risk for patients who were prescribed at least one antipsychotic medication at the time of COVID-19 infection (Fisher's exact test P = 0.009, OR = 11.1, 95% confidence interval: 1.4-96.0). This result remains significant after adjusting for age, gender, housing context and dementia (Logistic regression P = 0.035, Beta = 2.4). Furthermore, we found that most patients who survived COVID-19 (88.4%) recovered to pre-COVID baseline in terms of psychiatric symptoms. Comparison of pre- and post-COVID assessments of CGI-S for 33 patients who recovered from COVID-19 were not significantly different. CONCLUSION: We observed a higher COVID-19 mortality associated with concurrent antipsychotics use in older patients receiving behavioral health services. The majority of patients in our geriatric clinic who recovered from COVID-19 appeared to return to their pre-COVID psychiatric function. More precise estimates of the risk associated with antipsychotic treatment in older patients with COVID-19 and other underlying factors will come from larger datasets and meta-analyses.