Rita Cafaro’s research while affiliated with University of Milan and other places

Background: While bipolar disorder is strongly linked to an increased risk of suicide, recent evidence has challenged the assumption that mixed symptoms play a distinct role in suicidal ideation beyond depressive severity. This study examines how depressive, hypo/manic, and mixed features influence suicidal ideation in individuals with bipolar disorder. Data from 903 participants in the Stanley Foundation Bipolar Network (1995–2002) were analyzed to assess associations between mood states, classified by the Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C) and the Young Mania Rating Scale (YMRS), and suicidal ideation, measured using IDS-C item 18, using generalized estimating equations. Results: Depressive symptoms were strongly associated with suicidal ideation (OR = 21.98, 95% CI: 15.31–31.54). Moderate hypo/manic symptoms also conferred risk (OR = 3.11, 95% CI: 1.51–6.49), and milder hypo/mania showed a weaker but significant association (OR = 1.74, 95% CI: 1.05–2.89). The highest suicidal ideation was observed in individuals with hypo/mania featuring mixed symptoms (OR = 29.43), exceeding that of depression or depression with mixed features (OR = 21.98). However, findings diverged based on modeling approach: in continuous predictor models, SI was driven solely by depressive symptom severity, with no significant association observed for hypo/mania or its interaction with depression. In contrast, when mood states were categorized using clinically meaningful thresholds, hypo/mania with mixed features emerged as a distinct contributor to suicidal ideation risk. Conclusion: These findings underscore the need for integrating both dimensional and categorical approaches to mood state classification in research on suicidality in bipolar disorder.

Suicide is a global phenomenon, with more than 700,000 people worldwide taking their own life yearly. Both natural and human-made disaster may have a detrimental effect on suicidal behaviors both in the short-term and in the long-term. Many studies focused on the acute impact of the COVID-19 pandemic on suicidality. The aim of the study was to analyze demographic and clinical features of subjects accessing the emergency rooms for suicidality during the second epidemic wave of COVID-19 in five emergency departments in Lombardy (Italy). A retrospective chart review was conducted in the five emergency departments for the period 4 June – 31 December 2020, and during the same time lapse in 2019. For all subjects accessing for suicidality, socio-demographic and clinical data were collected and compared between the two years. No differences between the two years were found for sex, triage priority level, history of substance abuse, factor triggering suicidality and discharge diagnosis. During 2020 a greater proportion of subjects did not show any previous mental disorder, however, more subjects were already taking anxiolytic medications before the admission. Among a range of possible risk factors, attempted suicide, depression diagnosis and taking medications before the admission were found to be predictor of admission to psychiatric inpatient units. Characterizing subjects prone to suicidality during the second wave of the COVID-19 pandemic, our study provides hints for mid-term causes of suicidality and possible preventive measures that could be helpful in the course and after massive infectious outbreaks.

Background: The COVID-19 pandemic greatly impacted healthcare workers (HWs) around the world. Italy was the first Western country hit by the pandemic, and several studies have been published targeting the mental health burden held by Italian HWs. Notwithstanding, only a few studies focused on the impact of COVID-19 on HWs’ levels of functioning. Methods: An online survey was distributed to HWs in Italy through physicians’ and nurses’ associations, social networks, and researchers’ direct contacts, between 4 April and 13 May 2020. Participants provided sociodemographic, work-related, and pandemic-related data and filled out a set of psychometric questionnaires (Patient Health Questionnaire-9—PHQ-9, General Anxiety Disorder-7—GAD-7, Impact of Event Scale—Revised—IES-R, and Work and Social Adjustment Scale—WSAS). Results: The final sample included 1041 HWs (mean age 45.01 ± 11.62, 63.9% females). In total, 58.1% of the subjects screened positive on the GAD-7, 27.5% on the PHQ-9, and 25.9% on the IES-R. Furthermore, 67.4% showed a significant level of impairment in functioning according to the WSAS, while 35.8% reached scores of moderate or worse impairment. In the multiple linear regressions, screening positive on any of the psychometric scales and being exposed to unusual suffering significantly predicted worse scores in all WSAS domains (p < 0.05). Having a history of mental disorders significantly predicted worse scores in the WSAS domain of work ability (p = 0.002), while being the parent of children younger than 18 years significantly predicted worse WSAS family functioning scores (p < 0.001). Conclusions: Our results corroborate extant data about the impact of the COVID-19 pandemic on HWs’ mental health and shed light on its detrimental effect on functioning. Tailored interventions should be designed in order to support HWs during times of crisis.

Background Sleep pattern alteration is a core feature of bipolar disorder (BD), often challenging to treat and affecting clinical outcomes. Suvorexant, a hypnotic agent that decreases wakefulness, has shown promising results in treating primary insomnia. To date, data on its use in BD are lacking. This study evaluated the efficacy and tolerability of adjunctive suvorexant for treatment-resistant insomnia in BD patients. Methods Thirty-six BD outpatients (19 BDI, 69.4% female, 48.9 [±15.2] years) were randomized for 1 week to double-blind suvorexant (10–20 mg/day) versus placebo. Then, all subjects who completed the randomized phase were offered open suvorexant for 3 months. Subjective total sleep time (sTST) and objective total sleep time (oTST) were assessed. Results During the randomized control trial (RCT) phase, an overall increase in the oTST emerged, which was statistically significant for the Cole–Kripke algorithm ( p = 0.035). The comparison between the suvorexant and placebo groups was limited by significant differences between measurements at baseline. During the open phase, no significant improvement was detected relative to either sTST and oTST. No adverse events nor major intolerances were reported. Discussion Efficacy results are inconsistent. During the RCT phase, only a small increase in the objective oTST emerged, while during the open phase, no significant improvement was detected. While this is the first ever study of suvorexant in BD-related insomnia, the limitation of the small sample and the high rate of dropouts limits the generalizability of these findings. Larger studies are needed to assess suvorexant in treating BD-related insomnia.

Introduction: The longitudinal course of bipolar disorder (BD) is associated with an active process of neuroprogression, characterized by structural brain alterations and progressive functional impairment. In the last decades, a growing need of a standardized staging model for BD arose, with the aim of a more appropriate definition of stage-specific clinical manifestations and the identification of more customized therapeutic tools. Areas covered: The authors review the literature on clinical aspects, neurobiological correlates and treatment issues related to BD progression. Thereafter, they address the definition, constructs, and evolution of the staging concept, focusing on the clinical applications of BD staging models available in literature. Expert opinion: Although several staging models for BD have been proposed to date, their application in clinical practice is still relatively scant. This may have a detrimental impact on the clinical and therapeutic management of BD, in terms of early and proper diagnosis as well as tailored treatment interventions according to the different stages of illness. Future research efforts should tend to the integration of recent insights on neuroimaging and epigenetic markers, toward a standardized and multidimensional staging model.

Objective Psychiatric disorders burden the peripartum period, often requiring psychopharmacological treatment, including antidepressants. Efficacy and tolerability of antidepressants are influenced by the physiological changes of the peripartum and individual metabolic profiles, which in turn can be modified by pregnancy. The objective of this study is to assess the relationship between antidepressants’ pharmacokinetic profiles during pregnancy and individual metabolic profiles, along with the efficacy of the treatment. Methods In total 87 outpatients with diagnoses of bipolar disorder, major depression, anxiety, obsessive-compulsive disorder and post-traumatic stress disorder who required antidepressant treatment during pregnancy were recruited. Genotyping analysis of hepatic cytochrome P450 (CYPs) individual isoforms was performed. Antidepressants’ blood concentrations and psychometric assessments were collected at five time points. Antidepressants’ cord blood concentrations were assessed at birth. Results Sertraline showed greater stability in plasma concentrations and a lower placental penetrance index. Most of the antidepressants’ concentrations below the therapeutic range were found in women with an extensive/ultrarapid metabolic profile. Antidepressants mainly metabolized by CYP2C19 were less frequently below the therapeutic range compared with antidepressants metabolized by CYP2D6. Conclusions Pregnancy modulates cytochrome activity and drugs’ pharmacokinetics. Genotyping analysis of CYPs isoforms and therapeutic drug monitoring might be used to guide clinicians in a well-tolerated treatment of psychiatric symptoms in pregnant women.

Objective The COVID-19 pandemic impacted mental health across different groups, including healthcare workers (HWs). To date, few studies focused on potential positive aspects that may follow the exposure to the pandemic. We investigated the prevalence of posttraumatic stress disorder (PTSD) in Italian HWs and whether posttraumatic growth (PTG) dimensions affected the risk of suicidal ideation (SI) during the first COVID-19 wave. Methods An online self-report survey was conducted between April and May 2020. Sociodemographic data, information about COVID-19-related stressful events, Impact of the Event Scale-revised, and Post-Traumatic Growth Inventory-Short Form (PTGI-SF) scores were collected and compared between participants. Patient Health Questionnaire-9 scores were also collected to assess SI through item 9. Multivariate logistic regression was used to assess the relationship between PTGI and SI. Results Among 948 HWs, 257 (27.0%) reported a provisional PTSD diagnosis. The median PTGI-SF score was 24. Participants reporting PTSD symptoms had higher scores in the Spiritual change , Appreciation of life , and New possibilities domains, and in the total PTG scale. A total of 100 HWs (10.8%) screened positive for SI. Improvements in Relating to others domain of PTGI-SF (odds ratioOR: .46; 95% confidence interval: .25–.85) were associated with lower odds of SI. Conclusions COVID-19 pandemic has been indicated as a risk factor for SI, also among HWs. PTG may have a protective role on suicide risk. Improvements in Relating to others domain reduced odds of SI, consistently with the role of loneliness and lack of connectedness with others in enhancing suicidal risk.

Background: Long-acting injectable paliperidone can improve adherence in psychotic patients and reduce relapses and healthcare resource utilization (HRU). This study compares the effectiveness of the three-monthly paliperidone palmitate (PP3M) with the one-monthly formulation (PP1M) and investigates reasons that hinder the use of PP3M in real-world settings. Methods: The authors conducted a three-phase observational study. For subjects recruited from six psychiatric services in Milan, HRU outcomes of PP3M prescription were evaluated through a 12-month mirror-image design (phase 1) and a comparison of HRU of PP1M-only subjects and PP3M subjects during the year prior to PP3M initiation (phase 2). Lastly, they conducted a survey among physicians concerning reasons for not switching to PP3M (phase 3). Results: A total of 119 subjects (61 on PP3M and 58 on PP1M) were included. One year after PP3M initiation, outpatients' visits decreased significantly. Comparing PP3M with PP1M subjects, no significant difference was found in HRU. Perception of patient's unstable clinical condition was the main reason for maintaining PP1M (32.8%), followed by the need for monthly monitoring (19.7%). Conclusion: PP3M initiation was associated with an overall HRU reduction. Subjects switched to PP3M had similar HRU when compared to those who did not, suggesting similar clinical conditions in both groups.