Anxiety and depression played a central role in the COVID-19 mental distress: A network analysis.

INTRODUCTION: Psychological, socio-demographics, and clinical factors play an important role in patients with COVID-19, but their relationship is complex. The network approach might be used to disentangle complex interactions in different systems. Using data from a multicentre, cross-sectional, survey among patients with COVID-19 in Spain (July-November 2020), we investigated the network structure of mental disorders symptoms, social support, and psychological resilience, and changes in network structures according to the presence of a pre-existing mental disorder or hospitalization for COVID-19. METHODS: Subjects completed a survey to evaluate sociodemographic characteristics, COVID-19 infection status, resilience, social support, and symptoms of depression, anxiety disorders, post-traumatic stress disorder, panic attacks, and substance use disorder. 2084 patients with COVID-19 were included in the analysis. Network analysis was conducted to evaluate network and bridge centrality, and the network properties were compared between COVID-19 patients with and without a history of lifetime mental disorder, and between hospitalized and non-hospitalized patients. LIMITATIONS: Generalization of our findings may be difficult since differences in network connectivity may exist in different populations or samples. RESULTS: Anxiety and depression showed high centrality in patients with COVID-19 and anxiety showed the highest bridge influence in the network. Resilience and social support showed a low influence on mental disorder symptoms. Global network estimations show no statistically significant changes between patients with and without pre-existing mental disorders or between hospitalized and non-hospitalized patients. CONCLUSIONS: Anxiety might be a key treatment target in patients with COVID-19 since its treatment might prevent other mental health adverse outcomes.

Psychotropic drug repurposing for COVID-19: A Systematic Review and Meta-Analysis.

Several psychotropic drugs, including antidepressants (AD), mood stabilizers, and antipsychotics (AP) have been suggested to have favorable effects in the treatment of COVID-19. The aim of this systematic review and meta-analysis was to collect evidence from studies concerning the scientific evidence for the repurposing of psychotropic drugs in COVID-19 treatment. Two independent authors searched PubMed-MEDLINE, Scopus, PsycINFO, and ClinicalTrials.gov databases, and reviewed the reference lists of articles for eligible articles published up to 13th December 2021. All computational, preclinical and clinical (observational and/or RCTs) studies on the effect of any psychotropic drug on Sars-CoV-2 or patients with COVID-19 were considered for inclusion. We conducted random effect meta-analyses on clinical studies reporting the effect of AD or AP on COVID-19 outcomes. 29 studies were included in the synthesis: 15 clinical, 9 preclinical, and 5 computational studies. 9 clinical studies could be included in the quantitative analyses. AD did not increase the risk of severe COVID-19 (RR= 1.71; CI 0.65-4.51) or mortality (RR=0.94; CI 0.81-1.09). Fluvoxamine was associated with a reduced risk of mortality for COVID-19 (OR=0.15; CI 0.02-0.95). AP increased the risk of severe COVID-19 (RR=3.66; CI 2.76-4.85) and mortality (OR=1.53; CI 1.15-2.03). Fluvoxamine might be a possible candidate for psychotropic drug repurposing in COVID-19 due to its anti-inflammatory and antiviral potential, while evidence on other AD is still controversial. Although AP are associated with worse COVID-19 outcomes, their use should be evaluated case to case and ongoing treatment with antipsychotics should be not discontinued in psychiatric patients.

Upward trends in eating disorders, self-harm, and suicide attempt emergency admissions in female adolescents after COVID-19 lockdown.

INTRODUCTION: Increased mental health problems have been reported in children and adolescents related to the COVID-19 lockdown and its immediate aftermath, especially among adolescent females. However, the longer-term impact of persistent quarantine measures and social restrictions on this population is yet to be further explored. MATERIALS AND METHODS: We compared the number of children/adolescents admissions to the psychiatric emergency department (ED) of Hospital Clínic de Barcelona during the COVID-19 lockdown and the following year with the numbers of admissions the year before lockdown, adjusting for variations in the population. We also conducted separate analyses by gender, age group, and diagnostic categories. Finally, we also repeated the analyses considering the cumulated deficit/excess since the start of the lockdown. Statistical significance was estimated using binomial tests with Bonferroni correction. RESULTS: A total of 2425 admissions were recorded. Globally, admission rates decreased during the lockdown (46%) and progressively increased during the one-year aftermath (43% by spring 2021). This increase was particularly high in adolescent females (85%) while unclear in children and/or males. The main diagnostic categories involved were anxiety, depressive, and eating disorders, as well as self-harm behavior, suicidal ideation, and suicide attempts. The increase in eating disorders, self-harm behavior, and suicide attempts admissions in female adolescents remained statistically significant when considering the cumulated deficit/excess. CONCLUSIONS: We found increased ED admissions during the aftermath of the COVID-19 lockdown among adolescent females. We recommend strengthening the attention to this population to provide adequate specialized care and prevention strategies.

Undetermined predominant polarity in a cohort of bipolar disorder patients: Prevalent, severe, and overlooked.

OBJECTIVES: Predominant polarity (PP) is a concept used to define patients with bipolar disorder (BD) as presenting a tendency to manifest depressive (DPP) or manic (MPP) episodes. Still, the high percentage of patients with an undetermined PP (UPP), has been overlooked in most studies. Thus, we aimed to study UPP and outline its socio-demographic, clinical, and treatment-related features. METHODS: Patients were recruited from a BD specialized unit. The sample was divided into three groups according to PP and socio-demographic and clinical variables were compared. Significant variables at univariate comparisons were included in multivariate logistic regression with UPP as the dependent variable. RESULTS: A total of 708 BD patients were included, of which 437 with UPP (61.7%). UPP was associated with a higher number of affective relapses, when compared with DPP or MPP (χ2= 28.704, p<0.001). Mixed episodes (OR=1.398; CI=1.118-1.749), aggressive behaviour (OR=1.861; CI=1.190-2.913), seasonality (OR=2.025; CI= 1.289-3.501) and treatment with lamotrigine (OR= 2.101; CI=1.244-3.550) were significantly associated with UPP at the logistic regression. LIMITATIONS: Recall bias may have occurred due to mixed episode diagnostic criteria change over the years. No data on the patients' follow-up has been reported on predominant polarity changes. CONCLUSIONS: UPP is associated with a higher number of relapses, and different clinical variables related to a severe course of illness. Considering PP in patients with BD may guide the choice for differential treatment approaches having an impact on BD course of illness and patients' prognosis and recovery.

Evaluating maintenance electroconvulsive therapy in Bipolar Disorders: 3-year mirror-image study.

BACKGORUND: Maintenance electroconvulsive therapy (mECT) is underused in the treatment of bipolar disorder (BD). We aimed to study the real-life effectiveness of mECT in BD. METHODS: Naturalistic 3-year mirror-image study in individuals diagnosed with BD who underwent mECT at a tertiary hospital. Intra-subject comparisons of psychiatric hospitalization were performed using McNemar test. Days and number of psychiatric hospitalizations before and during mECT were compared through wilcoxon signed-rank test. Mean annual days and mean annual number of psychiatric hospitalizations per patient were compared by means of the rate ratio (RR) estimation through a generalized estimating equation (GEE) model. RESULTS: A total of 43 patients were included and 37 required psychiatric hospitalization during the study. The use of mECT showed an effectiveness of 62.2% for preventing psychiatric hospitalizations (p<0.01). We found significant reduction in days and number of psychiatric hospitalizations during mECT compared to before mECT (p<0.01). Comparison of the 3-year period before/during mECT showed a reduction in mean annual days (RR=0.14; 95%CI: 0.07-0.29) and mean annual number (RR=0.24; 95%CI: 0.13-0.43) of psychiatric hospitalizations, without substantial changes for adjusted models for gender and age of onset of the illness. LIMITATIONS: The main limitations of this study consisted of the mirror-image retrospective naturalistic study design, the relatively small sample size, and possibly patient selection bias. CONCLUSIONS: mECT reduced the number of psychiatric hospitalizations and hospitalization days in BD. The use of mECT outlines a mood stabilizing effect in BD. This naturalistic study supports the effectiveness of mECT in BD across several mood states.

Antipsychotic-Associated Weight Gain and Clinical Improvement Under Clozapine Treatment.

BACKGROUND: Antipsychotic-associated weight gain is a common adverse effect with several negative outcomes in the clinical evolution of patients, which might also affect patients' self-identity from physical appearance and imply treatment discontinuation. However, recent research has drawn attention to an unexpected clinical improvement associated with weight gain, mostly in patients under treatment with clozapine or olanzapine. METHODS: Twenty-three treatment-resistant psychosis patients initiating clozapine were evaluated. Longitudinal psychopathological assessment through the Positive and Negative Syndrome Scale (PANSS) and anthropometric evaluation were performed at baseline, week 8, and 18. RESULTS: Body mass index (BMI) change during clozapine treatment was associated with clinical improvement measured with PANSS total score at week 8 (P = 0.021) while showed a trend at week 18 (P = 0.058). The PANSS general score was also associated with weight gain at week 8 (P = 0.022), whereas negative subscale score showed a trend at week 8 (P = 0.088) and was associated between week 8 and 18 (P = 0.018). Sex differences applied at week 8 for PANSS total score, where clinical improvement was significantly associated with BMI in male subjects (P = 0.024). We also stratified for time to initiate clozapine, finding significant associations in negative symptom at week 8 (P = 0.023) and week 18 (P = 0.003) for subjects, which started clozapine after 3 years of illness. CONCLUSIONS: Our results suggest that in subjects initiating clozapine, clinical improvement is associated with BMI increase, mostly in negative symptom and in patients after 3 years of antipsychotic use. Our findings were already described in the preantipsychotic era, suggesting some pathophysiological mechanism underlying both conditions.

Duration of untreated illness and bipolar disorder: time for a new definition? Results from a cross-sectional study.

BACKGROUND: We primarily aimed to explore the associations between duration of untreated illness (DUI), treatment response, and functioning in a cohort of patients with bipolar disorder (BD). METHODS: 261 participants with BD were recruited. DUI was defined as months from the first affective episode to the start of a mood-stabilizer. The functioning assessment short test (FAST) scores and treatment response scores for lithium, valproate, or lamotrigine according to the Alda Scale Total Score (TS) were compared between patients with short (<24 months) or long DUI. Differences in FAST scores among good (GR; TS≥7), poor (PR; TS=2-6), or non-responders (NR; TS<2) to each mood-stabilizer were analyzed. Linear regression was computed using the FAST global score as the dependent variable. RESULTS: DUI and FAST scores showed no statistically significant correlation. Patients with a longer DUI showed poorer response to lithium (Z=-3.196; p<0.001), but not to valproate or lamotrigine. Response to lithium (ß=-1.814; p<0.001), number of hospitalizations (ß=0.237; p<0.001), and illness duration (ß=0.160; p=0.028) were associated with FAST total scores. GR to lithium was associated with better global functioning compared to PR or NR [H=27.631; p<0.001]. LIMITATIONS: The retrospective design could expose our data to a recall bias. Also, only few patients were on valproate or lamotrigine treatment. CONCLUSIONS: Poor functioning in BD could be the result of multiple affective relapses, rather than a direct effect of DUI. A timely diagnosis with subsequent effective prophylactic treatment, such as lithium, may prevent poor functional outcomes in real-world patients with BD.

Identifying clinical clusters with distinct trajectories in first-episode psychosis through an unsupervised machine learning technique.

The extreme variability in symptom presentation reveals that individuals diagnosed with a first-episode psychosis (FEP) may encompass different sub-populations with potentially different illness courses and, hence, different treatment needs. Previous studies have shown that sociodemographic and family environment factors are associated with more unfavorable symptom trajectories. The aim of this study was to examine the dimensional structure of symptoms and to identify individuals' trajectories at early stage of illness and potential risk factors associated with poor outcomes at follow-up in non-affective FEP. One hundred and forty-four non-affective FEP patients were assessed at baseline and at 2-year follow-up. A Principal component analysis has been conducted to identify dimensions, then an unsupervised machine learning technique (fuzzy clustering) was performed to identify clinical subgroups of patients. Six symptom factors were extracted (positive, negative, depressive, anxiety, disorganization and somatic/cognitive). Three distinct clinical clusters were determined at baseline: mild; negative and moderate; and positive and severe symptoms, and five at follow-up: minimal; mild; moderate; negative and depressive; and severe symptoms. Receiving a low-dose antipsychotic, having a more severe depressive symptomatology and a positive family history for psychiatric disorders were risk factors for poor recovery, whilst having a high cognitive reserve and better premorbid adjustment may confer a better prognosis. The current study provided a better understanding of the heterogeneous profile of FEP. Early identification of patients who could likely present poor outcomes may be an initial step for the development of targeted interventions to improve illness trajectories and preserve psychosocial functioning.

Changing trends in psychiatric emergency service admissions during the COVID-19 outbreak: Report from a worldwide epicentre.

BACKGROUND: During the COVID-19 pandemic, a structural reorganization was imposed on public health systems. Psychiatry services were also affected with the imposed reduction of non-urgent consultations. We aim to explore the effect of these changes on a Psychiatry Emergency Service during COVID-19 lockdown in Spain. METHODS: A retrospective analysis was performed on all patients admitted to our Psychiatric Emergency Service 90 days before and after March 14th, 2020, the first day of lockdown in Spain. Extracted data were compared between the two periods. Poisson regression analysis was performed to analyze changes in admission rates. RESULTS: 1,958 psychiatric emergency admissions were analyzed. Although the number of admissions decreased by 37.9%, we observed a significant increase in the percentage of acute psychiatric hospitalization during the lockdown. Anxiety spectrum disorders accumulated the greatest significant decrease in admission rates during the lockdown. On the other hand, a significant increase in admissions rates was found in patients with dementia, autism spectrum disorders, and substance use disorders during the lockdown. LIMITATIONS: This study was conducted in a single psychiatric emergency service, preventing a generalization of our results. The comparison time period might have biased our results due to the influence of external factors. CONCLUSION: Mental health consequences of COVID-19 are becoming apparent. A reduction of admission rates for anxiety disorders might be related telepsychiatry implementation during the lockdown. Other conditions particularly vulnerable to the routine changes and lack of social support have suffered the most, and efforts should be placed to treat these situations.

Adverse outcomes during pregnancy and major congenital malformations in infants of patients with bipolar and schizoaffective disorders treated with antiepileptic drugs: A systematic review. / Dzialania niepozadane w czasie ciazy i powazne wrodzone wady rozwojowe u niemowlat pacjentek z zaburzeniami afektywnymi dwubiegunowymi i zaburzeniami schizoafektywnymi leczonych lekami przeciwpadaczkowymi: przeglad systematyczny.

OBJECTIVES: Antiepileptic drugs (AEDs), which are commonly used as a treatment for acute phases and prevention of relapses in bipolar disorder (BD) and schizoaffective disorder (SAD), have been often associated to adverse outcomes in pregnancy and major congenital malformations (MCM). We aimed to summarize available evidence assessing these outcomes when AEDs are used in pregnant women with BD and/or SAD. METHODS: We searched four databases from inception to 18 January, 2019. We included peer-reviewed observational studies on the use of AEDs in pregnant women with BD or SAD. We excluded studies not reporting data on BD or SAD, not specifying the AED or not assessing pregnancy outcomes or MCM. RESULTS: The pooled records amounted to 2,861. After duplicate removal and inclusion/exclusion criteria application, we included 9 observational studies assessing patients with BD and SAD. The AEDs evaluated were lamotrigine (LTG), valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), topiramate (TPR) and gabapentin (GBP). VPA and CBZ were the AED most commonly associated to MCM. LTG showed the best safety profile. Higher rates of complications during pregnancy were observed in treated and untreated women with BD compared to healthy controls. CONCLUSIONS: AEDs may produce adverse outcomes in pregnancy and MCM in children of pregnant women with BD or SAD, showing higher risks at higher doses. LTG could be considered in this type of patients, given the low rate of adverse events. VPA and CBZ use should be avoided during pregnancy.

Food craving and consumption evolution in patients starting treatment with clozapine.

BACKGROUND: Antipsychotic-induced weight gain has been especially related to clozapine and olanzapine. Underlying mechanisms in relation to food preferences with an increased food craving and consumption of specific nutrients have not been extensively studied in patients with serious mental illness (SMI). We aim to describe specific food preferences (craving) and subsequent food consumption in SMI patients starting clozapine, as well as their possible relation to weight and body mass index (BMI). METHODS: An observational prospective follow-up study (18 weeks) was conducted in a cohort of 34 SMI patients who started clozapine due to resistant-psychotic symptoms. Anthropometric measures, Food Craving Inventory (FCI), and a food consumption frequency questionnaire were evaluated at baseline, weeks 8 and 18 of treatment. Statistical analysis included generalized estimating equations models with adjustment for potential confounding factors. RESULTS: No longitudinal changes over time were found across the different food craving scores after 18 weeks of treatment. However, adjusted models according to BMI status showed that the normal weight (NW) group presented an increased score for the "complex carbohydrates/proteins" food cravings (- 0.67; 95% CI [- 1.15, - 0.19]; P = 0.010), while baseline scores for "fast-food fats" cravings were significantly higher in the overweight/obese (OWO) group in comparison with NW patients (NW, 2.05; 95% CI [1.60, 2.49]; OWO, 2.81, 95% CI [2.37, 3.25]; P = 0.016). When considering if food craving could predict weight gain, only increments in "fast-food fats" cravings were associated (ß = - 5.35 ± 1.67; 95% CI [- 8.64, - 2.06]; P = 0.001). CONCLUSIONS: No longitudinal differences were found for any of the food craving scores evaluated; however, in the NW group, food craving for "complex carbohydrates/proteins" changed. Thus, changes in "fast-food fats" cravings predicted weight increase in this sample. Interventions targeting food preferences may help to mitigate weight gain in patients starting treatment with clozapine.