Anxiety, Stress and Depression in COVID-19 Survivors From an Italian Cohort of Hospitalized Patients: Results From a 1-Year Follow-Up.

Background: Mental health-related symptoms can persist over time beyond the most common respiratory clinical features of COVID-19. A recent meta-analysis underlined that mental health sequalae may be relevant for COVID-19 survivors and reported the following prevalence rates: 20% for post-traumatic stress disorder, 22% for anxiety, 36% for psychological distress, and 21% for depression. In the context of a multi-disciplinary follow-up project, we already investigated the mid-term (4 months) psychiatric outcomes in a sample of COVID-19 survivors. Patients were re-assessed after 1-year since hospital discharge. Methods: Follow-up conducted after 1 year involved 196 individuals recovered from COVID-19. Patients were assessed with a multi-disciplinary approach; including both a clinical interview performed by an experienced psychiatrist, trained in the use of the Mini-International Neuropsychiatric Interview (MINI) to assess the presence of anxiety, stress, and depressive symptoms and the following self-administered questionnaires: Beck Anxiety Inventory, Beck Depression Inventory-II, Resilience Scale for Adults, Impact of Event Scale, and COVID-19 Peritraumatic Distress Index (CPDI). Results: Anxiety (p < 0.0001) and depressive (p < 0.0003) symptoms registered at the clinical interview showed a significant improvement from the 4 to 12-months follow-up. Logistic regression model showed that female gender (p = 0.006), arterial hypertension (p = 0.01), obesity (0.04), anxiety (p < 0.0001), and depressive (p = 0.02) symptoms at 4-months follow-up were associated with persistence of anxiety symptoms at 12 months. At logistic regression analysis female gender (p = 0.02) and depressive symptoms at 4-months follow-up (p = 0.01) were associated with depressive symptoms after 12 months. Conclusion: Severity of the disease in the acute phase, in this study, was not a determining factor in identifying subjects at risk of developing clinically relevant anxiety and depression as a consequence of COVID-19 disease. Findings from the logistic regressions suggest that the factors most affecting depression and anxiety in COVID survivors after 12 months were female gender, the presence of anxiety and depression after 4 months and some physical symptoms, not necessarily COVID-related. Impact of infection and consequent hospitalization for COVID-19 did no longer represent a relevant issue for depressive symptoms, compared to other general factors.

Mid-term Psychiatric Outcomes of Patients Recovered From COVID-19 From an Italian Cohort of Hospitalized Patients.

Background: Although the usual primary clinical manifestation of Coronavirus disease (COVID-19) is respiratory, several non-respiratory symptoms have been described, including neuropsychiatric ones. The aim of this study was to investigate the mid-term mental health outcomes in patients recovered from COVID-19, 3-4 months after discharge from the University Hospital Maggiore della Carità, Novara, Italy. Furthermore, we investigated the possible association of the mid-term mental health consequences of the COVID-19 infection with patients' clinical current status, persistent physical impairment and severity of acute phase of the disease. Methods: Prospective study involving 238 individuals recovered from COVID-19. In the context of a multi-disciplinary approach, patients' assessment included both a clinical interview performed by an experienced psychiatrist, trained in the use of the Mini-International Neuropsychiatric Interview to assess the presence of anxiety and depressive symptoms and self-administered questionnaires: Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), Resilience Scale for Adults (RSA), Impact of Event Scale (IES). Results: At the psychiatric assessment 32.9 and 29.5% of participants showed anxiety and depressive symptoms, respectively. Changes in appetite and sleep patterns emerged for 15.6 and 31.2% of patients. According to the self-administered questionnaires, 7.1% of participants had moderate-severe anxiety levels (BAI), while 10.5% had mild to severe depression (BDI-II). Twenty-six (11%) participants were referred to further psychiatric consultation. Psychiatric symptoms showed no correlation with acute COVID-19 severity; in our sample patients with depressive symptoms at the clinical interview, as well as those with mild to severe levels of depression according to BDI-II scores, had lower forced expiratory volume in the 1st second (FEV1) values than those without and greater odds for persistent, poor tolerance for physical efforts. Conclusions: As could be expected, an approach including both a psychiatric interview and the use of self-administered questionnaires is likely to capture the psychiatric outcome of patients recovered from COVID-19 better than questionnaires alone. Anxiety and depressive symptoms at follow-up had no correlation with the severity of COVID acute manifestations, but rather with ongoing and persistent physical symptoms. Further studies and longer follow-up duration will allow a better understanding of the complex relationship between residual physical symptoms, quality of life and psychological health.

Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge.

Importance: Although plenty of data exist regarding clinical manifestations, course, case fatality rate, and risk factors associated with mortality in severe coronavirus disease 2019 (COVID-19), long-term respiratory and functional sequelae in survivors of COVID-19 are unknown. Objective: To evaluate the prevalence of lung function anomalies, exercise function impairment, and psychological sequelae among patients hospitalized for COVID-19, 4 months after discharge. Design, Setting, and Participants: This prospective cohort study at an academic hospital in Northern Italy was conducted among a consecutive series of patients aged 18 years and older (or their caregivers) who had received a confirmed diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection severe enough to require hospital admission from March 1 to June 29, 2020. SARS-CoV-2 infection was confirmed via reverse transcription-polymerase chain reaction testing, bronchial swab, serological testing, or suggestive computed tomography results. Exposure: Severe COVID-19 requiring hospitalization. Main Outcomes and Measures: The primary outcome of the study was to describe the proportion of patients with a diffusing lung capacity for carbon monoxide (Dlco) less than 80% of expected value. Secondary outcomes included proportion of patients with severe lung function impairment (defined as Dlco <60% expected value); proportion of patients with posttraumatic stress symptoms (measured using the Impact of Event Scale-Revised total score); proportion of patients with functional impairment (assessed using the Short Physical Performance Battery [SPPB] score and 2-minute walking test); and identification of factors associated with Dlco reduction and psychological or functional sequelae. Results: Among 767 patients hospitalized for severe COVID-19, 494 (64.4%) refused to participate, and 35 (4.6%) died during follow-up. A total of 238 patients (31.0%) (median [interquartile range] age, 61 [50-71] years; 142 [59.7%] men; median [interquartile range] comorbidities, 2 [1-3]) consented to participate to the study. Of these, 219 patients were able to complete both pulmonary function tests and Dlco measurement. Dlco was reduced to less than 80% of the estimated value in 113 patients (51.6%) and less than 60% in 34 patients (15.5%). The SPPB score was suggested limited mobility (score <11) in 53 patients (22.3%). Patients with SPPB scores within reference range underwent a 2-minute walk test, which was outside reference ranges of expected performance for age and sex in 75 patients (40.5%); thus, a total of 128 patients (53.8%) had functional impairment. Posttraumatic stress symptoms were reported in a total of 41 patients (17.2%). Conclusions and Relevance: These findings suggest that at 4 months after discharge, respiratory, physical, and psychological sequelae were common among patients who had been hospitalized for COVID-19.

An observational study of Venlafaxine and CYP2D6 in clinical practice.

BACKGROUND: Venlafaxine (V) is a serotonin-norepinephrine selective reuptake inhibitor, mainly metabolized by cytochrome P4502D6 (CYP2D6). CYP2D6 polymorphisms result in a variety of phenotypes: poor (PMs), intermediate (IMs), extensive (EMs), and ultrarapid metabolizers (UMs). PMs usually show poor tolerance to drugs metabolized by CYP2D6, while UMs need greater doses. The aim of this study was to evaluate the impact of CYP2D6 genotype on V dosage, therapeutic response, and side effects in a clinical outpatient setting. METHODS: 47 patients with Major Depressive Disorder, treated with V 75 - 300 mg/day, underwent CYP2D6 genotyping using the INFINITI-CYP2D6 assay. Duration of treatment and clinical outcome (Clinical Global Impression [CGI] effectiveness index) were assessed. RESULTS: CGI assessment was performed after 6 weeks, 6 months, and 1 year of treatment with a V median dose of 150 mg/day. CYP2D6 genotyping resulted in 1 PM, 3 IMs, 42 EMs, and 1 UM. The UM took the greatest V dose (375 mg) without side effects; IMs/PMs took moderate/high doses of V (150 - 300 mg) without adverse effects; EMs displayed high response variability. CONCLUSIONS: PM/IM patients responded to V differently than expected according to genotype. However, the UM patient responded to a dosage higher than the usual therapeutic range and without developing side effects, suggesting an association between CYP2D6 gene duplication and the therapeutic efficacy of venlafaxine. The CYP2D6 genotyping may thus provide clinicians with a potential explanation for those patients requiring greater doses of CYP2D6 substrates in order to obtain the same therapeutic efficacy.

Asenapine in clinical practice: preliminary results from a naturalistic observational study.

OBJECTIVE: Asenapine, a second-generation antipsychotic, seems to be an effective and tolerable alternative to other treatments for patients with manic or mixed episodes. The objective of our naturalistic observational study was to identify asenapine responders and remitters and to compare responders vs. non-responders and remitters vs. non-remitters, as far as clinical and socio-demographic features are concerned. MATERIALS AND METHODS: We recruited patients with diagnosis of manic episode in bipolar I (BD I) or schizoaffective disorder, with clinical indication to asenapine treatment. Patients' assessment was performed at baseline (T0), after 1 week (T1) and after 4 weeks (T2) of treatment, with the Young Mania Rating Scale (YMRS; T0,T1,T2) and Hamilton Rating Scale for Depression (HAM-D; T0, T2). According to YMRS scores, we classified patients as early improvers, treatment responders, and treatment remitters. RESULTS: A significant decrease was found in HAM-D scores from baseline to T2, with no significant difference between remitters and non-remitters or responders vs. non-responders.The YMRS score significantly improved from baseline to T2, with a significant difference between remitters and non-remitters, but not between responders and non-responders. No difference was found between responders and non-responders as far as socio-demographic and clinical variables, and questionnaire baseline scores are concerned. Remitters and non-remitters showed significant differences in baseline YMRS scores, which were lower in the first and in the type of current episode, which was more frequently moderate in the former than in the latter. CONCLUSIONS: Early improvers comprised 51% of subjects, responders comprised 91.9% and remitters comprised 59.4%. Elderly manic patients with neurological impairment and/or dementia may have poorer therapeutic outcomes. Our results suggest that: 1) decision regarding treatment discontinuation should be cautious in patients who fail to have an early response to asenapine; 2) different diagnosis (BDor schizoaffective disorder) does not seem to have a significant impact on asenapine efficacy; 3) remission with asenapine is more likely to happen for less severe manic episodes. Further naturalistic studies on larger samples are required to support our findings.