Characterization of Bipolar Disorder I and II: Clinical Features, Comorbidities, and Pharmacological Pattern.

Objective: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition provides precise diagnostic criteria to differentiate between bipolar disorder (BD) type I and II; nevertheless, it can be challenging to come up with the right diagnosis. The aim of this study is to evaluate the sociodemographic differences, clinical features, comorbidities, and pharmacological pattern between patients with BD type I and II. Methods: A total of 680 patients with BD type I and II were consecutively recruited to our psychiatry department. A semi-structured interview was used to collect several information. Results: Patients with BD type I were mostly males, single, with a lower current age, and unemployed compared to patients with BD type II. Furthermore, patients with BD type I showed an earlier age at onset and a significant higher prevalence of psychotic and residual symptoms, a higher number of hospitalizations, and involuntary admissions. On the other hand, patients with BD type II were associated with a significant higher prevalence of lifetime suicide attempts, psychiatric comorbidities, and use of alcohol. Finally, antidepressant drugs were prescribed more often to patients with BD type II, while antipsychotics and mood stabilizers were mostly prescribed in patients with BD type I. Conclusion: the differentiation of the 2 nosologic bipolar diagnosis is in line with the current scientific interest, confirming the existence of a markedly different profile between BD type I and II. This differentiation could reduce the heterogeneity of bipolar presentation in research, optimize clinical assessment, and increase the interest in developing more precise and individualized therapeutic strategies, also implementing psychosocial therapies.

The Role of Hopelessness in Patients With Borderline Personality Disorder.

BACKGROUND: The goal of this study was to evaluate specific characteristics associated with hopelessness, potentially correlated with coping strategies, sensory profile, and alexithymia in patients with borderline personality disorder (BPD). MATERIALS AND METHODS: Two hundred twenty-four (N=224) inpatients completed a clinical interview with administration of the Beck Hopelessness Scale (BHS), the Adolescent/Adult Sensory Profile (AASP), the Coping Orientation to Problems Experienced Inventory (COPE), and the Toronto Alexithymia Scale (TAS). RESULTS: Hopelessness was significantly associated with female gender, more hospitalizations, current suicidal ideation, number of suicide attempts, current and lifetime medication abuse, and alcohol misuse. Furthermore, patients with BHS ≥ 9 had higher scores in low registration, sensory sensitivity and sensation avoiding in AASP, higher rate of alexithymia, and the use of maladaptive coping strategies. CONCLUSIONS: Hopelessness in BPD was associated with higher severity of illness, alternative process sensory input from the environment, reduced ability to cope with stressful events, and alexithymia. Therefore, a routine assessment of hopelessness in patients with BPD could lead to better and more specific therapeutic strategies.

Limbic Network Derangement Mediates Unawareness of Apathy in Mild Cognitive Impairment due to Alzheimer's Disease: Clues from [18F]FDG PET Voxel-Wise Analysis.

Background: Discrepancy between caregiver and patient assessments of apathy in mild cognitive impairment (MCI) is considered an index of apathy unawareness, independently predicting progression to AD dementia. However, its neural underpinning are uninvestigated. Objective: To explore the [18F]FDG PET-based metabolic correlates of apathy unawareness measured through the discrepancy between caregiver and patient self-report, in patients diagnosed with MCI. Methods: We retrospectively studied 28 patients with an intermediate or high likelihood of MCI-AD, progressed to dementia over an average of two years, whose degree of apathy was evaluated by means of the Apathy Evaluation Scale (AES) for both patients (PT-AES) and caregivers (CG-AES). Voxel-based analysis at baseline was used to obtain distinct volumes of interest (VOIs) correlated with PT-AES, CG-AES, or their absolute difference (DISCR-AES). The resulting DISCR-AES VOI count densities were used as covariates in an inter-regional correlation analysis (IRCA) in MCI-AD patients and a group of matched healthy controls (HC). Results: DISCR-AES negatively correlated with metabolism in bilateral parahippocampal gyrus, posterior cingulate cortex, and thalamus, PT-AES score with frontal and anterior cingulate areas, while there was no significant correlation between CG-AES and brain metabolism. IRCA revealed that MCI-AD patients exhibited reduced metabolic/functional correlations of the DISCR-AES VOI with the right cingulate gyrus and its anterior projections compared to HC. Conclusions: Apathy unawareness entails early disruption of the limbic circuitry rather than the classical frontal-subcortical pathways typically associated with apathy. This reaffirms apathy unawareness as an early and independent measure in MCI-AD, marked by distinct pathophysiological alterations.

Reduction of peripersonal comfort space correlate with eating disorder symptoms in young adolescents: a network analysis approach.

Background: Peripersonal Space (PS) is represented as the immediate area surrounding an individual. The extent of PS changes in relation to several factors, including emotional states, type of relationship or psychopathology. Attachment anxiety has an impact on the social adaptability of peripersonal space and anxiety and fear are associated with an expansion of peripersonal space, possibly serving as a mechanism of self-protection. Peripersonal space appears to be intricately linked to various psychiatric conditions like anxiety disorders and converging evidence suggests that social maladjustment may predict or exacerbate eating disorder symptoms expression. Methods: Fifty-eight healthy adolescents (38F, 20M) performed a comfort distance estimation task to assess peripersonal space. The Adolescent/Adult Sensory Profile (AASP) was used to assess sensory profiles and the SAFA protocol to investigate psychopathological aspects. Data was analysed using Network Analysis, estimating a Gaussian Graphical Models with a Bayesian approach. Results: We found that the task related to comfort estimation distance demonstrated a correlation with the visual scale of the Adolescent/Adult Sensory Profile (AASP). Additionally, a correlation was observed with the Eating Disorder scale of the SAFA protocol. The touch scale also was negatively correlated with Eating disorder symptoms but not with the comfort estimation task. Conclusion: Our results demonstrate a relation between peripersonal space and eating disorder symptoms in healthy adolescents in line with previous findings in adults with eating disorders diagnosis. These findings suggest that socio-emotional difficulties may be possible precursors or reinforce for the development of an eating disorder symptoms.

The role of community resilience as a protective factor in coping with mental disorders in a sample of psychiatric migrants.

Background: Over the past decade migration to Italy has increased significantly for various reasons including armed conflicts. Generally, the migration process is exposed to different risk factors during different periods of migration, which can compromise well-being and promote the onset or exacerbation of mental disorders. A community with resources and the perception of one's community as resilient can be important protective factor in the context of migration. Purpose: This study aims to understand which variables in migration predict an increase in perceived community resilience and to understand the role of community resilience in the relationship between mental disorders and subjective well-being in a sample of 100 adult migrants at the first consultation interview in the ambulatories of Psychiatry Unit. Methods: After defining the inclusion and exclusion criteria, migrants were asked to fill out self-report questionnaires to collect socio-demographic data and to assess perception of mental disorders, perceived community resilience and perception of subjective well-being. Descriptive analysis, simple regression, and moderation analyses were conducted to test the hypotheses. Results: The results show that the variable meaning attributed to the community with reference to the host community, migration with someone, and longer duration of stay in Italy contribute to increased perceptions of community resilience. In addition, a direct negative effect of mental disorders on subjective well-being and the moderating role of community resilience in relationship between mental disorders and subjective well-being have been demonstrated. Conclusions: This result underscores the importance of perceived community resilience in mitigating the negative effects of mental disorders on subjective well-being. Perceiving one's community as more resilient seems to protect against the impact of mental disorders on subjective well-being. Our results support an ecological model of migrants' mental health that values the community and its resources in coping with mental disorders in the context of migration.

Advances in the management of bipolar disorder in children and adolescents: an update on the literature.

INTRODUCTION: Early diagnosis and treatment concerning bipolar disorder (BD) are related to a better functioning over the long-term period. Although pharmacotherapy is indicated for approximately all youths with BD, nearly one-third of patients do not receive adequate medications for their condition. AREAS COVERED: The authors discuss the available scientific evidence from the current literature about the management of BD in both children and adolescents, giving particular focus to the efficacy and tolerability of the available pharmacological agents. Studies were identified searching MEDLINE and retrieved from reference listings of relevant articles and through consultation with experts in the field. EXPERT OPINION: Many D2-blockers, approved by the Food and Drug Administration (FDA) based on their antimanic properties in youths, are related to both short- and long-term side effects. Lurasidone was found to be effective for the treatment of acute juvenile bipolar depression, while lithium for the treatment and recurrence prevention of manic/mixed episodes. The most common anticonvulsants were found to be most useful as adjunctive antimanic agents in non-responders to first-line monotherapies. No data was found to support the use of antidepressants in juvenile BD.

Psychological dimensions in alcohol use disorder: comparing active drinkers and abstinent patients.

Background: Alcohol use disorder (AUD) is a major public health concern due to its various physical, psychological, and social consequences. Despite regulatory differences, abstinence remains the primary treatment objective. Addressing the multifaceted nature of alcohol use disorder requires a comprehensive approach. Methods: 150 AUD patients (66%male) with a mean age of 54.10 ± 11.3 years were recruited for the study. Depression, impulsivity, alexithymia, and hopelessness were assessed to determine if there were significant differences in these dimensions between abstinent (N=72) and active drinkers (N=78). Results: The study found significant differences in the psychological dimensions scores, active drinkers exhibited higher levels of depression, impulsivity, alexithymia, and hopelessness compared to abstinent patients. Conclusion: Treatment outcomes for patients with AUD vary between regulatory agencies, but abstinence remains the safest and most preferred objective in managing AUD. Prioritizing abstinence-oriented interventions is crucial for achieving long term recovery and minimizing relapse risk. These results emphasize the intricate relationship between AUD and mental health issues, highlighting the need for comprehensive interventions addressing both alcohol consumption and associated psychological distress. Promoting abstinence (or at least reducing alcohol consumption) not only preserves mental health but also prevents life-threatening consequences such as suicide.

Obsessive-Compulsive Disorder as an Epiphenomenon of Comorbid Bipolar Disorder? An Updated Systematic Review.

BACKGROUND: Bipolar disorder (BD) and obsessive-compulsive disorder (OCD) comorbidity is an emerging condition in psychiatry, with relevant nosological, clinical, and therapeutic implications. METHODS: We updated our previous systematic review on epidemiology and standard diagnostic validators (including phenomenology, course of illness, heredity, biological markers, and treatment response) of BD-OCD. Relevant papers published until (and including) 15 October 2023 were identified by searching the electronic databases MEDLINE, Embase, PsychINFO, and Cochrane Library, according to the PRISMA statement (PROSPERO registration number, CRD42021267685). RESULTS: We identified 38 new articles, which added to the previous 64 and raised the total to 102. The lifetime comorbidity prevalence ranged from 0.26 to 27.8% for BD and from 0.3 to 53.3% for OCD. The onset of the two disorders appears to be often overlapping, although the appearance of the primary disorder may influence the outcome. Compared to a single diagnosis, BD-OCD exhibited a distinct pattern of OC symptoms typically following an episodic course, occurring in up to 75% of cases (vs. 3%). Notably, these OC symptoms tended to worsen during depressive episodes (78%) and improve during manic or hypomanic episodes (64%). Similarly, a BD course appears to be chronic in individuals with BD-OCD in comparison to patients without. Additionally, individuals with BD-OCD comorbidity experienced more depressive episodes (mean of 8.9 ± 4.2) compared to those without comorbidity (mean of 4.1 ± 2.7). CONCLUSIONS: We found a greater likelihood of antidepressant-induced manic/hypomanic episodes (60% vs. 4.1%), and mood stabilizers with antipsychotic add-ons emerging as a preferred treatment. In line with our previous work, BD-OCD comorbidity encompasses a condition of greater nosological and clinical complexity than individual disorders.

The Role of Lurasidone in Managing Depressive Symptoms in People with Schizophrenia: A Review.

BACKGROUND: Schizophrenia is a severe mental disorder characterized by positive, negative, affective, and cognitive symptoms. Affective symptoms in patients with schizophrenia have traditionally been overlooked or even neglected because they are not considered as fundamental as positive and negative symptoms in the choice of medication. METHODS: This paper aims to systematically evaluate the efficacy and safety of lurasidone in the treatment of depressive symptoms of schizophrenia. RESULTS: Lurasidone appears to be particularly effective on the depressive symptomatology of schizophrenia while also alleviating the positive and negative symptoms associated with the illness. CONCLUSIONS: The efficacy of lurasidone in treating patients with first-episode psychosis who present with predominant depressive symptoms suggests that this medication may be a valuable treatment option not only for established cases of schizophrenia but also for individuals in the early stages of the illness. The good tolerability of lurasidone is an important factor that may positively influence treatment decisions.

Global trends in youth suicide from 1990 to 2020: an analysis of data from the WHO mortality database.

Background: Suicide is a serious but preventable public health concern at the global level, showing relevant geographical differences. This study aims to monitor global temporal and geographical patterns in suicide mortality in pre-adolescents, adolescents, and young adults (i.e., aged 10-24 years), from 1990 to 2020 or the most recent available year. Methods: Using the World Health Organisation mortality database, we conducted an analysis on a subset of 52 countries with valid and high-quality data. We computed age-standardised suicide rates (ASR) by sex, country, and calendar year, and performed a joinpoint regression analysis to identify significant changes in the temporal suicide trends over the studied period. Findings: High variability in suicide rates and trends was observed, with a male-to-female ratio of two to five. Between 1990 and 2020, most European countries reported declining suicide trends, with some exceptions. In particular, alarming trends emerged in the United Kingdom, with annual rises of 2.5% (95% CI: 1.6-3.5) since 2005 among males and 8.5% (95% CI: 4.7-12.6) since 2012 among females. The most favorable trends and lowest suicide rates were in Southern Europe, with 3.1/100,000 persons in Italy (2020) and 3.5/100,000 persons in Spain (2021) among males, and 0.9/100,000 persons in Italy (2020) and 1.1/100,000 persons in Romania (2019) among females. Conversely, the highest rates were in Central-Eastern Europe, with 10.2/100,000 males in the Russian Federation (2019) and 10.0/100,000 males in Poland (2002). Higher suicide rates and significant increases were reported in not European areas. The highest ASR was 15.5/100,000 males in the United States of America, with an annual increase of 3.8% (95% CI: 3.1-4.5) among males in 2009-2020 and 6.7% (95% CI: 5.6-7.8) among females in 2007-2017, followed by a levelling off. Interpretation: Temporal and geographical comparisons of suicide mortality should be interpreted with caution due to potential misclassification or under-reporting of suicide deaths in some countries. Funding: None.

A Prospective Multicenter Longitudinal Analysis of Suicidal Ideation among Long-COVID-19 Patients.

Long coronavirus disease 19 (COVID-19) is an emerging multifaceted illness with the pathological hallmarks of chronic inflammation and neuropsychiatric symptoms. These pathologies have also been implicated in developing suicidal behaviors and suicidal ideation (SI). However, research addressing suicide risk in long COVID-19 is limited. In this prospective study, we aim to characterize SI development among long-COVID-19 patients and to determine the predictive power of inflammatory markers and long-COVID-19 symptoms-including those of psychiatric origin-for SI. During this prospective, longitudinal, multicenter study, healthy subjects and long-COVID-19 patients will be recruited from the University Hospital of Geneva, Switzerland, the University of Genova, the University of Rome "La Sapienza", and the University of San Francisco. Study participants will undergo a series of clinic visits over a follow-up period of 1 year for SI assessment. Baseline and SI-onset levels of inflammatory mediators in plasma samples, along with 12 long-COVID-19 features (post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal disturbance, palpitations, changes in sexual desire/capacity, loss/change of smell/taste, thirst, chronic cough, chest pain, and abnormal movements) will be collected for SI risk analysis. The proposed enrollment period is from 15 January 2024 to 15 January 2026 with targeted recruitment of 100 participants for each study group. The anticipated findings of this study are expected to provide important insights into suicide risk among long-COVID-19 patients and determine whether inflammation and psychiatric comorbidities are involved in the development of SI in these subjects. This could pave the way to more effective evidence-based suicide prevention approaches to address this emerging public health concern.

Characterization of Psychiatric Inpatients: The Role of Gender Differences in Clinical and Pharmacological Patterns.

BACKGROUND: Severe mental disorders that require hospitalization are disabling conditions that contribute to the burden of mental diseases. They pose increased clinical challenges and highlight the need to thoroughly explore variables emerging from daily clinical practice. In this study, we assessed to what extent gender differences may characterize a large population of psychiatric inpatients. METHODS: We conducted a cross-sectional study in 2 Italian teaching medical centers, which included 2358 patients who were consecutively admitted to the psychiatric emergency units. We explored and characterized gender differences for variables such as prevalence of psychiatric diagnosis, presence of suicidal ideation, suicide attempts, age at onset of psychiatric illness, presence of substance or alcohol abuse, length of stay, number of hospitalizations, presence of involuntary admission, type of discharge from the hospital, and pharmacological treatment at discharge. RESULTS: Female patients were primarily diagnosed with bipolar disorder or personality disorders. Female patients had a significantly higher prevalence of lifetime suicide attempts (23.1% vs. 16.5%, P<0.001) and a longer length of hospitalization (11.43±10.73 d vs. 10.52±10.37 d, t=-2.099, gl=2356, P=0.036) compared with male patients. Male patients had more involuntary admissions (25.1% vs. 19.7%, χ2=9.616, gl=1, P=0.002), more use of illicit substances (34.1% vs. 20.9%, χ2=51.084, gl=1, P<0.001), and higher rates of alcohol abuse (21.3% vs. 14.7%, χ2=17.182, gl=1, P<0.001) compared with female patients. Finally, antidepressants and lithium were prescribed more frequently to the female patients, whereas other mood stabilizers were more often prescribed to the male patients. CONCLUSIONS: Our real-world results highlighted gender differences among patients with severe mental disorders admitted to psychiatric units, and suggest further investigations that may help in understanding trajectories accompanying disabling clinical conditions.

The interplay between mentalization, personality traits and burnout in psychiatry training: Results from a large multicenter controlled study.

BACKGROUND: A better characterization of educational processes during psychiatry training is needed, both to foster personal resilience and occupational proficiency. METHODS: An adequate coverage of medical residents at the national level was reached (41.86% of the total reference population, 29 out of 36 training centers-80.55%). Controls were recruited among residents in other medical specialties. All participants were assessed by questionnaires to evaluate early life experiences, attachment style, personality traits, coping strategies, emotional competencies. A Structural Equation Model (SEM) framework was employed to investigate the interplay between individual factors. RESULTS: A total sample of 936 people was recruited (87.9% response-rate; 645 residents in psychiatry, 291 other medical residents). Psychiatry trainees reported a higher prevalence of adverse childhood experiences (emotional abuse, emotional neglect, physical neglect), greater attachment insecurity (anxious or avoidant) in comparison to other medical trainees. Psychiatry residents also reported higher social support-seeking as a coping strategy, lower problem-orientation, and lower transcendence. Lower neuroticism, higher openness to experience, and higher emotional awareness were also observed in psychiatry trainees. Psychiatry training was associated with a redefinition of conflict management skills as a function of seniority. The SEM model provided support for an interplay between early traumatic experiences, mentalization skills (coping strategies, emotion regulation), interpersonal competencies and occupational distress. CONCLUSIONS: The findings of the present study supported a theoretical model based on mentalization theory for the interactions between personal and relational competencies in psychiatry training, thus providing potential target of remodulation and redefinition of this specific process of education.

T-cell immunophenotype correlations with cortical thickness and white matter microstructure in bipolar disorder.

BACKGROUND: Inflammation and immunological alterations, such as T-cell and cytokine changes, are implicated in bipolar disorder (BD), with some evidence linking them to brain structural changes (e.g., cortical thickness (CT), gray matter (GM) volume and white matter (WM) microstructure). However, the connection between specific peripheral cell types, such as T-cells, and neuroimaging in BD remains scarcely investigated. AIMS OF THE STUDY: This study aims to explore the link between T-cell immunophenotype and neuroradiological findings in BD. METHODS: Our study investigated 43 type I BD subjects (22 depressive, 21 manic) and 26 healthy controls (HC), analyzing T lymphocyte immunophenotype and employing neuroimaging to assess CT for GM and fractional anisotropy (FA) for WM. RESULTS: In lymphocyte populations, BD patients exhibited elevated CD4+ and CD4+ central memory (TCM) cells frequencies, but lower CD8+ effector memory (TEM) and terminal effector memory (TTEM) cells. Neuroimaging analysis revealed reduced CT in multiple brain regions in BD patients; and significant negative correlations between CD4 + TCM levels and CT of precuneus and fusiform gyrus. Tract-based spatial statistics (TBSS) analysis showed widespread alteration in WM microstructure in BD patients, with negative and positive correlations respectively between FA and radial diffusivity (RD) and CD4 + TCM. Additionally, positive and negative correlations were found respectively between FA and RD and the CD8 + TEM and CD8 + TTEM subsets. CONCLUSIONS: Our research revealed distinct T lymphocyte changes and brain structure alterations in BD, underscoring possible immune-brain interactions, warranting further study and therapeutic exploration.

Sensation seeking correlates with increased white matter integrity of structures associated with visuospatial processing in healthy adults.

Introduction: The ability to process sensory information is an essential adaptive function, and hyper- or hypo-sensitive maladaptive profiles of responses to environmental stimuli generate sensory processing disorders linked to cognitive, affective, and behavioral alterations. Consequently, assessing sensory processing profiles might help research the vulnerability and resilience to mental disorders. The research on neuroradiological correlates of the sensory processing profiles is mainly limited to the young-age population or neurodevelopmental disorders. So, this study aims to examine the structural MRI correlates of sensory profiles in a sample of typically developed adults. Methods: We investigated structural cortical thickness (CT) and white matter integrity, through Diffusion Tensor Imaging (DTI), correlates of Adolescent/Adult Sensory Profile (AASP) questionnaire subscales in 57 typical developing subjects (34F; mean age: 32.7 ± 9.3). Results: We found significant results only for the sensation seeking (STS) subscale. Positive and negative correlations emerged with fractional anisotropy (FA) and radial diffusivity (RD) in anterior thalamic radiation, optic radiation, superior longitudinal fasciculus, corpus callosum, and the cingulum bundle. No correlation between sensation seeking and whole brain cortical thickness was found. Discussion: Overall, our results suggest a positive correlation between sensation seeking and higher white matter structural integrity in those tracts mainly involved in visuospatial processing but no correlation with gray matter structure. The enhanced structural integrity associated with sensation seeking may reflect a neurobiological substrate linked to active research of sensory stimuli and resilience to major psychiatric disorders like schizophrenia, bipolar disorder, and depression.

Immunomodulatory Effects of Clozapine: More Than Just a Side Effect in Schizophrenia.

Recent evidence suggests a possible relationship between the immune system and schizophrenia spectrum disorders (SSDs), as neuroinflammation appears to play a role in major psychiatric conditions. Neuroinflammation is as a broad concept representing a physiological protective response to infection or injury, but in some cases, especially if chronic, it may represent an expression of maladaptive processes, potentially driving to clinical dysfunction and neurodegeneration. Several studies are concurrently highlighting the importance of microglia, the resident immune cells of the central nervous system, in a huge number of neurodegenerative diseases, including multiple sclerosis, Alzheimer's and Parkinson's diseases, as well as SSDs. A more fundamental phenomenon of maladaptive coupling of microglia may contribute to the genesis of dysfunctional brain inflammation involved in SSDs, from the onset of their neurophenomenological evolution. Clozapine and other antipsychotic drugs seem to express a provable immunomodulant effect and a more specific action on microglia, while neuroactive steroids and nonsteroidal anti-inflammatory drugs may reduce some SSDs symptoms in add-on therapy. Given these theoretical premises, this article aims to summarize and interpret the available scientific evidence about psychotropic and anti-inflammatory drugs that could express an immunomodulant activity on microglia.

Drug-drug interactions between COVID-19 therapeutics and psychotropic medications.

INTRODUCTION: The coronavirus (COVID-19) pandemic has led to as well as exacerbated mental health disorders, leading to increased use of psychotropic medications. Co-administration of COVID-19 and psychotropic medications may result in drug-drug interactions (DDIs), that may compromise both the safety and efficacy of both medications. AREAS COVERED: This review provides an update of the current evidence on DDIs between COVID-19 and psychotropic medications. The interactions are categorized into pharmacokinetic, pharmacodynamic, and other relevant types. A thorough literature search was conducted using electronic databases to identify relevant studies, and extract data to highlight potential DDIs, clinical implications, and management strategies. EXPERT OPINION: Understanding and managing potential DDIs between COVID-19 and psychotropic medications is paramount to ensuring safe and effective treatment of patients with COVID-19 and mental illness. Awareness of the diverse spectrum of DDIs, vigilant monitoring, and judicious dose modifications, while choosing pharmacotherapeutic options with low risk of interaction whenever possible, are necessary. Ongoing and future investigations should continue to review the dynamic landscape of COVID-19 therapeutic modalities and their interactions with psychotropic medications.

Rethinking headache as a global public health case model for reaching the SDG 3 HEALTH by 2030.

The 2030 Agenda for Sustainable Development sets out, through 17 Sustainable Development Goals (SDGs), a path for the prosperity of people and the planet. SDG 3 in particular aims to ensure healthy lives and promote well-being for all at all ages and includes several targets to enhance health. This review presents a "headache-tailored" perspective on how to achieve SDG 3 by focusing on six specific actions: targeting chronic headaches; reducing the overuse of acute pain-relieving medications; promoting the education of healthcare professionals; granting access to medication in low- and middle-income countries (LMIC); implementing training and educational opportunities for healthcare professionals in low and middle income countries; building a global alliance against headache disorders. Addressing the burden of headache disorders directly impacts on populations' health, as well as on the possibility to improve the productivity of people aged below 50, women in particular. Our analysis pointed out several elements, and included: moving forward from frequency-based parameters to define headache severity; recognizing and managing comorbid diseases and risk factors; implementing a disease management multi-modal management model that incorporates pharmacological and non-pharmacological treatments; early recognizing and managing the overuse of acute pain-relieving medications; promoting undergraduate, postgraduate, and continuing medical education of healthcare professionals with specific training on headache; and promoting a culture that favors the recognition of headaches as diseases with a neurobiological basis, where this is not yet recognized. Making headache care more sustainable is an achievable objective, which will require multi-stakeholder collaborations across all sectors of society, both health-related and not health-related. Robust investments will be needed; however, considering the high prevalence of headache disorders and the associated disability, these investments will surely improve multiple health outcomes and lift development and well-being globally.