Understanding the potential of digital therapies in implementing the standard of care for depression in Europe.

Depressive disorders represent the largest proportion of mental illnesses, and by 2030, they are expected to be the first cause of disability-adjusted life years [1]. The COVID-19 pandemic exacerbated prevalence and burden of depression and increased the occurrence of depressive symptoms in general population [2]. The urgency of implementing mental health services to address new barriers to care persuaded clinicians to use telemedicine to follow patients and stay in touch with them, and to explore digital therapeutics (DTx) as potential tools for clinical intervention [2]. The combination of antidepressants and psychotherapy is widely recommended for depression by international guidelines [3] but is less frequently applied in real-world practice. Commonly used treatments are pharmacological, but while being effective, some aspects such as adherence to the drug regimen, residual symptoms, resistance, lack of information, and stigma may hinder successful treatment. In case of less severe depression, standalone psychological therapies should be the first-line treatment option [3], but access to trained psychotherapists remains inequitable. DTx are evidence-based therapies driven by software programs to treat or complement treatment of a specific disease. DTx are classified as Medical Devices, and given their therapeutic purpose, they need to be validated through randomized controlled clinical trials, as for drug-based therapies. In the last 10 years, studies of digital interventions have proliferated; these studies demonstrate that digital interventions increase remission rates and lower the severity of depressive symptoms compared with waitlist, treatment as usual, and attention control conditions [4]. Despite the efficacy demonstrated in clinical trials, many of these tools never reach real-life patients; thus, it might be necessary to implement DTx in the public health system to expand access to valid treatment options. In this framework, DTx represent a good opportunity to help people with depression receive optimal psychotherapeutic care [5].

Evaluation of telepsychiatry during the COVID-19 pandemic across service users, carers and clinicians: an international mixed-methods study.

BACKGROUND: Worldwide uptake of telepsychiatry accelerated during the COVID-19 pandemic. OBJECTIVE: To conduct an evaluation of the opinions, preferences and attitudes to telepsychiatry from service users, carers and clinicians in order to understand how telepsychiatry can be best used in the peri/post-COVID-19 era. METHODS: This mixed-methods, multicentre, international study of telepsychiatry was set in two sites in England and two in Italy. Survey questionnaires and focus group topic guides were co-produced for each participant group (service users, carers and clinicians). FINDINGS: In the UK, 906 service users, 117 carers and 483 clinicians, and in Italy, 164 service users, 56 carers and 72 clinicians completed the surveys. In all, 17 service users/carers and 14 clinicians participated in focus groups. Overall, telepsychiatry was seen as convenient in follow-ups with a specific purpose such as medication reviews; however, it was perceived as less effective for establishing a therapeutic relationship or for assessing acutely disturbed mental states. In contrast to clinicians, most service users and carers indicated that telepsychiatry had not improved during the COVID-19 pandemic. Most service users and carers reported that the choice of appointment modality was most often determined by the service or clinician. CONCLUSION AND RELEVANCE: There were circumstances in which telepsychiatry was seen as more suitable than others and clear differences in clinician, carer and service user perspectives on telepsychiatry. CLINICAL IMPLICATIONS: All stakeholders should be actively engaged in determining a hybrid model of care according to clinical features and service user and carer preferences. Clinicians should be engaged in training programmes on telepsychiatry.

Lurasidone in adolescents and adults with schizophrenia: from clinical trials to real-world clinical practice.

INTRODUCTION: Lurasidone is an atypical antipsychotic agent approved in the European Union for the treatment of schizophrenia in adults and adolescents (13-17 years). Clinical trials have shown a generally favorable balance between efficacy and tolerability. AREAS COVERED: This paper provides a review and commentary regarding the use of lurasidone in adults and adolescents with schizophrenia. The available information about efficacy, tolerability, dosing, and switching is analyzed, highlighting the strategies that may be most useful in real-world clinical practice. Virtual case studies, designed based on the authors' clinical experience with real-world patients, are provided. EXPERT OPINION: Lurasidone is efficacious in adolescents and adults in a wide range of symptoms of schizophrenia. Choosing the right dose for each patient and combining lurasidone with other medications is key to treatment success. Lurasidone has proven effective both in adolescents and adults in treating the acute phase of schizophrenia and reducing the risk of relapse. It has shown a relatively favorable tolerability profile, with minimal effects on metabolic parameters and prolactin levels.

The interplay between acute post-traumatic stress, depressive and anxiety symptoms on healthcare workers functioning during the COVID-19 emergency: A multicenter study comparing regions with increasing pandemic incidence.

BACKGROUND: Healthcare workers (HCWs) deployed to the frontline during the COVID-19 pandemic are at risk for developing mental disorders, with a possible impact on their wellbeing and functioning. The present study aimed at investigating post-traumatic stress symptoms (PTSS), anxiety and depressive symptoms and their relationships with impairment in the functioning impairment among frontline HCWs from three Italian regions differently exposed to the first wave of the COVID-19 emergency: Tuscany (low), Emilia-Romagna (medium) and Lombardy (high). METHODS: 514 frontline HCWs were consecutively enrolled in hospital units devoted to the treatment of COVID-19 patients. They completed the IES-R, PHQ-9 and GAD-7 to assess PTSS, depressive and anxiety symptoms respectively, and the WSAS to investigate functioning impairment. RESULTS: A total of 23.5% of HCWs reported severe PTSS, 22.4% moderate-severe anxiety symptoms, 19.3% moderate-severe depressive symptoms and 22.8% impairment in global functioning. HCWs from the higher-exposure regions reported significantly higher scores in all instruments than those from lower-exposure regions. In a multiple linear regression model, PTSS, depressive and anxiety symptoms presented a significant positive association with the functioning impairment. Both PTSS and depression resulted to be independently related to functioning impairment. LIMITATIONS: The cross-sectional design and the use of self-report instruments. CONCLUSIONS: Depressive and PTSS appear to be the greatest contributors to functioning impairment in HCWs exposed to a massive stressful sanitary event as the COVID-19 pandemic. A more accurate assessment of work-related mental health outcomes in such population could help planning effective prevention strategies and therapeutic interventions.

Cariprazine in Three Special Different Areas: A Real-World Experience.

Cariprazine is an antipsychotic medication which received approval from the US Food and Drug Administration for the treatment of schizophrenia in September 2015. Cariprazine is a dopamine D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Furthermore, although to a more limited extent, cariprazine also exhibits partial agonism at the level of 5-HT1A receptors, thus exerting an antidepressant effect in addition to the antipsychotic effect. The most commonly encountered adverse events are extrapyramidal symptoms and akathisia. Short-term weight gain appears infrequently. Cariprazine is not associated with any clinically meaningful alterations in metabolic variables, prolactin, or ECG QT interval. Cariprazine is also approved for the acute treatment of manic or mixed episodes associated with bipolar I disorder. Clinical trials of cariprazine are ongoing in patients with acute bipolar I depression and as adjunctive treatment to antidepressant therapy in patients with major depressive disorder. In this article, we present some significant clinical cases regarding the use of cariprazine, with the hope that our experience can provide insight or suggestions to be used in clinical practice.

Impact of COVID-19 on telepsychiatry at the service and individual patient level across two UK NHS mental health Trusts.

BACKGROUND: The effects of COVID-19 on the shift to remote consultations remain to be properly investigated. OBJECTIVE: To quantify the extent, nature and clinical impact of the use of telepsychiatry during the COVID-19 pandemic and compare it with the data in the same period of the 2 years before the outbreak. METHODS: We used deidentified electronic health records routinely collected from two UK mental health Foundation Trusts (Oxford Health (OHFT) and Southern Health (SHFT)) between January and September in 2018, 2019 and 2020. We considered three outcomes: (1) service activity, (2) in-person versus remote modalities of consultation and (3) clinical outcomes using Health of the Nation Outcome Scales (HoNOS) data. HoNOS data were collected from two cohorts of patients (cohort 1: patients with ≥1 HoNOS assessment each year in 2018, 2019 and 2020; cohort 2: patients with ≥1 HoNOS assessment each year in 2019 and 2020), and analysed in clusters using superclasses (namely, psychotic, non-psychotic and organic), which are used to assess overall healthcare complexity in the National Health Service. All statistical analyses were done in Python. FINDINGS: Mental health service activity in 2020 increased in all scheduled community appointments (by 15.4% and 5.6% in OHFT and SHFT, respectively). Remote consultations registered a 3.5-fold to 6-fold increase from February to June 2020 (from 4685 to a peak of 26 245 appointments in OHFT and from 7117 to 24 987 appointments in SHFT), with post-lockdown monthly averages of 23 030 and 22 977 remote appointments/month in OHFT and SHFT, respectively. Video consultations comprised up to one-third of total telepsychiatric services per month from April to September 2020. For patients with dementia, non-attendance rates at in-person appointments were higher than remote appointments (17.2% vs 3.9%). The overall HoNOS cluster value increased only in the organic superclass (clusters 18-21, n=174; p<0.001) from 2019 to 2020, suggesting a specific impact of the COVID-19 pandemic on this population of patients. CONCLUSIONS AND CLINICAL IMPLICATIONS: The rapid shift to remote service delivery has not reached some groups of patients who may require more tailored management with telepsychiatry.

Gender Differences in Misdiagnosis and Delayed Diagnosis among Adults with Autism Spectrum Disorder with No Language or Intellectual Disability.

Autism Spectrum Disorder (ASD) is often unrecognized, especially in mild forms and in women. Studies evaluating features associated with missed/misdiagnosis in men and women with ASD are warranted. 61 subjects (22 females, 39 males, age 28.5 ± 10.8 years) with ASD with no language/intellectual deficit were enrolled in the service for the treatment of psychiatric comorbidities in adults with ASD of the ASST Fatebenefratelli-Sacco in Milan (Italy). A detailed clinical history was gathered, and two self-report questionnaires (Autism Spectrum Quotient-AQ and Adult Autism Subthreshold Spectrum-AdAS Spectrum) were administered. 75.4% received their ASD diagnosis average eight years later than the first evaluation by mental health services. Compared to males, females showed a significantly greater delay in referral to mental health services and a significantly higher age at diagnosis of ASD. Among men, diagnostic delay inversely correlated with scores on the AdAS Spectrum total, Verbal communication, Empathy and Inflexibility and adherence to routine domains. Among women, diagnostic delay positively correlated with the Attention to detail score while the age at diagnosis of ASD positively correlated with the AdAS Spectrum Verbal communication and Restricted interests and rumination domain scores. Females were less likely to be correctly diagnosed and more likely to be misdiagnosed at first evaluation than men. Females reported significantly higher scores than men in the Hyper/Hyporeactivity to sensory input domain only among subjects who were misdiagnosed. Our findings provide gender-specific information about ASD patients seeking help for comorbid conditions and might be a primary ground for future research.

Emergency Psychiatric Consultations During and After the COVID-19 Lockdown in Italy. A Multicentre Study.

Aims: The aim was to analyse the psychiatric consultations in nine Italian hospital emergency departments, by comparing the lockdown and post-lockdown periods of 2020 with the equivalent periods of 2019. Methods: Characteristics of psychiatric consultations, patients, and drug prescriptions were analyzed. Joinpoint models were used to identify changes in the weekly trend of consultations. Results: A 37.5% decrease in the number of consultations was seen during the lockdown period and 17.9% after the lockdown. The number of individual patients seen decreased by 34.9% during the lockdown and 11.2% after the lockdown. A significant change in the number of consultations from week 11 to week 18 occurred, followed by a gradual increase. There was a higher percentage of patients with previous psychiatric hospitalizations during the lockdown period (61.1 vs. 56.3%) and a lower percentage after the lockdown (59.7 vs. 64.7%). During the lockdown there was a large increase in psychiatric consultations for substance use disorders, whereas more consultations for manic episodes occurred after the lockdown. A 3.4% decrease was observed in consultations for suicidal ideation and planning during the lockdown, followed by an upward rebound after the lockdown, along with an increase in consultations for suicide attempts. During lockdown antipsychotic and benzodiazepine prescriptions increased by 5.2 and 4.1%, respectively. After the lockdown, the number of compulsory hospitalizations was higher than in 2019. Conclusions: We observed a decrease of psychiatric consultations during and after the lockdown. There was an increase in consultations for manic episodes and suicidality after the lockdown. The focus of psychiatric services must remain high particularly in this latter period.

How Did COVID-19 Affect Suicidality? Data from a Multicentric Study in Lombardy.

The aim of the study was to describe the characteristics of subjects accessing the emergency rooms for suicidal behavior during the first epidemic wave of COVID-19 in three Emergency Departments (EDs) in Lombardy (Italy). A retrospective chart review was conducted for the period 8 March-3 June 2020, and during the same time frame in 2019. For all subjects accessing for suicidality, socio-demographic and clinical data were collected and compared between the two years. The proportion of subjects accessing for suicidality was significantly higher in 2020 than in 2019 (13.0 vs. 17.2%, p = 0.03). 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 mental disorders and were psychotropic drug-free. Women were more likely than men to receive inpatient psychiatric treatment, while men were more likely to be discharged with a diagnosis of acute alcohol/drug intoxication. Our study provides hints for managing suicidal behaviors during the still ongoing emergency and may be primary ground for further studies on suicidality in the course of or after massive infectious outbreaks.

PTSD and Depression in Healthcare Workers in the Italian Epicenter of the COVID-19 Outbreak.

BACKGROUND: Increasing evidence highlights the susceptibility of Healthcare Workers to develop psychopathological sequelae, including Post-Traumatic Stress Disorder (PTSD) and depression, in the current COronaVIrus Disease-19 (COVID-19) pandemic, but little data have been reported in the acute phase of the pandemic. OBJECTIVE: To explore Healthcare Workers' mental health reactions in the acute phase of the COVID-19 pandemic in the first European epicenter (Lodi/Codogno, Italy), with particular attention to post-traumatic stress and depressive symptoms and their interplay with other psychological outcomes. METHODS: 74 Healthcare Workers employed at the Azienda Socio Sanitaria Territoriale of Lodi (Lombardy, Italy) were recruited and assessed by means of the Impact of Event Scale- Revised, the Professional Quality of Life Scale-5, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 item, the Resilience Scale and the Work and Social Adjustment Scale. Socio-demographic and clinical variables were compared across three subgroups of the sample (No PTSD, PTSD only, PTSD and depression). RESULTS: A total of 31% of subjects endorsed a diagnosis of PTSD and 28.4% reported PTSD comorbid with major depression. Females were more prone to develop post-traumatic stress and depressive symptoms. Subjects with PTSD and depression groups showed high levels of PTSD, depression, burnout and impairment in functioning. Anxiety symptoms were higher in both PTSD and depression and PTSD groups rather than in the No PTSD group. CONCLUSION: Our results showed high rates of PTSD and depression among Healthcare Workers and their comorbidity overall being associated with worse outcomes. Current findings suggest that interventions to prevent and treat psychological implications among Healthcare Workers facing infectious outbreaks are needed.

Survey on centres and procedures for the diagnosis and treatment of adult ADHD in public services in Italy.

Attention deficit/hyperactivity disorder (ADHD) often persists into adulthood. Although its persistence and relative high prevalence, ADHD in adults is often underdiagnosed and undertreated in Italy, leading to poor clinical and functional outcomes, and higher costs of illness. The aims of the study were to identify the Italian mental health services for ADHD in adults, describe the diagnostic and treatment procedures they follow, and compare this offer with the recommendations of the German and English guidelines. The centres, that adopt a clinical and assessment protocol for adult ADHD diagnosis (carried out by specifically trained personnel) and prescribe pharmacological treatment for adult ADHD, were selected from the list of accredited services provided by the Appendix B.2 of the ISTISAN 16/37 Reports of the ISS. An ad-hoc survey including open-ended and close-ended questions was sent to each selected centre in February 2020. The overall picture resulting from the data analysis was compared with the recommendations of the German and English guidelines. The present survey shows that only a few centres are specialised in the diagnosis and treatment of ADHD in adults in Italy. Furthermore, there are no national guidelines for adult ADHD in Italy. The collected data also suggest that there is no a unified practice shared by the Centres both for the patient's transition from child and adolescent to adult mental health services and for the diagnostic-therapeutic process. It is therefore crucial to create specific protocols and develop national guidelines to better identify and diagnose ADHD in adults and provide targeted and more efficient multimodal treatments.

Sleep quality among adults with attention deficit hyperactivity disorder or autism spectrum disorder: which is the role of gender and chronotype?

Both Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) present increased prevalence rates of sleep difficulties, which persist into adulthood. However, it is still unclear whether in adults these disorders show specific sleep patterns and which role is played by comorbidities, circadian preferences and gender. This study aimed to describe and compare subjective measures of sleep in adults with ADHD and high-functioning ASD, in relation to the levels of anxiety and depression, chronotype and gender. In a sample of 136 adults (43 ADHD, 43 high-functioning ASD, 50 controls) subjective sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI), and clinical scales were used to assess chronotype and the levels of anxiety and depression. The three groups showed a significant difference in the distribution of chronotypes, with greater prevalence of an Evening chronotype among ASD compared to controls. The MANCOVA using PSQI subscale scores as dependent variables and MEQ-SA score and depression range as covariates showed that the three groups significantly differ in quality, latency, efficiency, and dysfunction scores with a significant differences between ASD and ADHD in efficiency and dysfunction. Compared to men, women showed higher scores on PSQI total and quality subscale across the three groups and higher duration scores only within ASD group. Our results indicate that both ADHD and ASD adults show unique sleep disturbances and suggest that ASD patients, especially women, may display more pronounced disordered sleep.

Treating schizophrenia with cariprazine: from clinical research to clinical practice. Real world experiences and recommendations from an International Panel.

BACKGROUND: Management of schizophrenia is sub-optimal in many patients. Targeting negative symptoms, among the most debilitating aspects of schizophrenia, together with positive symptoms, can result in significant functional benefits and dramatically improve quality of life for patients and their carers. Cariprazine, a partial agonist of the dopamine receptors D2/D3 has demonstrated effectiveness across symptom domains in clinical trials, particularly on negative symptoms. OBJECTIVE: To obtain a broader insight from clinicians with specific experience with cariprazine, on how it affects patient populations outside the clinical trial setting. METHODS: The panel addressed a series of psychopharmacologic topics not comprehensively addressed by the evidence-based literature, including characteristics of patients treated, dosing and switching strategies, duration of therapy, role of concomitant medications and tolerability as well as recommendations on how to individualize cariprazine treatment for patients with schizophrenia. RESULTS: Patients recommended for cariprazine treatment are those with first episodes of psychosis, predominant negative symptoms (maintenance/acute phase) and significant side effects (metabolic side effects, hyperprolactinemia, sedation) with other antipsychotics. When the long-term treatment of a lifetime illness is adequately weighted, cariprazine becomes one of the first-line medications, not only for patients with predominant negative symptoms but also for those with relatively severe positive symptoms, especially if they are at the first episodes and if a specific medication is added for symptoms such as agitation or insomnia. For instance, patients with agitation may also benefit from the combination of cariprazine and a benzodiazepine or another sedating agent. Cariprazine may be prescribed as add-on to medications such as clozapine, when that medication alone is ineffective for negative symptoms, and sometimes the first may be discontinued or its dose lowered, after a period of stability, leaving the patient on a better tolerated antipsychotic regimen. CONCLUSIONS: Based on real-world clinical experience, the panel considered that cariprazine, with its distinct advantages including pharmacokinetics/pharmacodynamics, good efficacy and tolerability, represents a drug of choice in the long-term management of schizophrenia not only for patients with predominant negative symptoms but also for those with positive symptoms.

Complicated Grief: What to Expect After the Coronavirus Pandemic.

The COVID-19 pandemic is one of the worst public health crises in a century, with an expected amount of deaths of several million worldwide and an even bigger number of bereaved people left behind. Although the consequences of this crisis are still unknown, a significant number of bereaved people will arguably develop Complicated Grief (CG) in the aftermath of this emergency. If the current pandemic is unprecedented, the grief following the coronavirus outbreak is likely to share features with grief related to natural disasters and after Intensive Care Unit (ICU) treatment. The aim of this paper is to review the most prominent literature on CG after natural disasters, as well as after diseases requiring ICU treatment. This body of evidence may be useful for helping bereaved people during the acute phase of the COVID-19 pandemic and for drawing clinical attention to people at risk for CG.

Mental Health in the Coronavirus Disease 2019 Emergency-The Italian Response.

Importance: This article briefly reports the experience of mental health services and the lessons learned during the coronavirus disease 2019 (COVID-19) crisis. In particular, this report offers opportunities to build on experience gained in managing the COVID-19 emergency in the Departments of Mental Health and Addiction (DMHAs) in Lombardy, the wealthiest Italian region, which has approximately 10 million inhabitants. Observations: Italy has a National Mental Health System divided into 134 DMHAs, 27 of which are in Lombardy. In the 4 weeks after the epidemic started, important changes occurred in the management of DMHAs in Lombardy. Many challenges have occurred in the management of health services. In many hospitals, entire wards, including some psychiatric wards, have been reorganized to admit patients with COVID-19, and many physicians and nurses have been diverted to wards managing patients with COVID-19. Most day facilities for patients with psychiatric needs have been temporarily closed, whereas in residential facilities, patients who usually are free to come and go during the day have had to be confined in the facilities with very limited or no leave. These changes have produced considerable stresses on people with severe mental disorders. Many outpatient clinics have limited appointments to those with the most urgent cases, and home visits, a common practice in most DMHAs, have been drastically reduced with potentially detrimental consequences for patients' well-being. Another potential detrimental consequence of being forced to stay at home has been an increase in the hours spent face to face with families with high amounts of conflict. Conclusions and Relevance: Departments of Mental Health need to be equipped with appropriate e-health technologies and procedures to cope with situations such as the COVID-19 pandemic. Additionally, interventions are needed to mitigate the potentially harmful consequences of quarantine. Departments of Mental Health should be able to assume a leadership position in the psychosocial management of disasterlike situations, and this requires the acquisition of new skills, notably how to correctly inform the population about risk, train and disseminate effective preventive and management procedures for disasters, support health personnel and rescuers, and support those experiencing bereavement.

Off-Label Use of Second-generation Antipsychotics in Bipolar Disorder: A Survey of Italian Psychiatrists.

Bipolar disorder (BD) is characterized by recurrent depressive and manic episodes. Lithium, valproate, lamotrigine, and some second-generation antipsychotics (SGAs) are the most typical pharmacological treatments for BD, the main goal being mood stabilization. However, despite these treatments, most patients continue to experience recurrent mood episodes and residual symptoms. Findings from several studies suggest that some SGAs may be beneficial beyond approved indications. The goal of the survey presented in this article was to examine Italian psychiatrists' attitudes concerning the off-label use of SGAs in depressive and maintenance phases of BD. A questionnaire about the off-label prescription of SGAs was e-mailed to 300 psychiatrists from Northern, Central, and Southern Italy affiliated with the Italian Society of Psychopharmacology (SINPF) to investigate the frequency of and motivation for off-label use of SGAs and evaluate the psychiatrists' attitude toward use of specific SGAs in BD; 202 questionnaires were completed. The respondents were equally distributed in terms of sex, and the mean age of respondents was 44.1 years. The majority of the sample reported use of SGAs for off-label indications either very often (16.7%), often (33.7%), or occasionally (34.7%). The main motivation for off-label use of the SGAs was the presence of published evidence (51.5%), followed by patients' nonresponse to previous treatment (37.1%). With regard to the use of specific SGAs in BD, off-label aripiprazole was considered appropriate for depressive episodes by 46% of the psychiatrists, followed by olanzapine which was considered appropriate by 33.7%. For maintenance treatment of BD, off-label asenapine was considered appropriate by 45% of the psychiatrists, followed by long-acting aripiprazole and olanzapine pamoate, which were considered appropriate by 37.1% and 23.8%, respectively. In summary, ~50% of Italian psychiatrists frequently (very often or often) prescribe SGAs for off-label indications. Given the relatively limited number of indicated effective treatments for BD, the use of some SGAs off-label may be considered appropriate when dealing with patients whose BD is resistant to medications with labeled indications for BD.

Pharmacological treatment of negative symptoms in schizophrenia: update and proposal of a clinical algorithm.

The clinical presentation of schizophrenia encompasses symptoms divided into three dimensions: positive, negative, and cognitive. Negative symptoms (NS), in particular, have a major impact on the quality of life of the affected subject, and, differing from positive symptoms, are often associated with a limited response to pharmacotherapy. To date, studies specifically investigating NS in schizophrenia are scant; therefore, proper selection of therapy for NS remains a major unmet medical need. Given the heterogeneity of the clinical presentation of schizophrenia, the treatment of NS, as well as therapy for other associated symptoms, should be largely individualized according to a patient's specific characteristics. In this paper, we review current knowledge on NS and construct a clinical algorithm for the treatment of schizophrenic conditions with pronounced NS. Overall, data from the literature suggest that second-generation antipsychotics, such as cariprazine and amisulpride, should be preferred over first-generation antipsychotics (FGAs), as they are associated with better functional outcomes and lower cognitive impairment. The combination of antipsychotics and antidepressants may also improve NS while addressing some affective disorders associated with schizophrenia; however, no clear information is available on the effects of this combination on primary NS or on the mechanism of action of the combination. In the proposed clinical algorithm, we suggest that cariprazine should be used as first-line treatment for patients with predominant NS, and that amisulpride should be considered as an alternative in cases of cariprazine failure. Further treatment lines may include the use of olanzapine and quetiapine, and add-on therapy with antidepressants.

ADHD in adults: clinical subtypes and associated characteristics.

INTRODUCTION: Attention Deficit Hyperactivity Disorder (ADHD) is an early onset clinical condition characterized by attention difficulties, hyperactivity and impulsivity which can persist across the lifespan, significantly influencing the evolutionary course and facilitating the rise of psychiatric comorbidities. The presence of different ADHD subtypes in adults is a heterogeneity factor to be recognized in order to orient prognosis and treatment, as indicated by studies that described differences in the characterization of different subtypes in relation to both severity and comorbidities. MATERIALS AND METHODS: In the present study we evaluated the socio-demographic and clinical characteristics of a sample of adults with ADHD and the characteristics associated with the different disorder subtypes. We described 60 patients aged between 18 and 65 years (mean age 34.1) with primary diagnosis of ADHD consecutively admitted to the Regional Centre for diagnosis and treatment of ADHD in adults in Milan. RESULTS: We observed high severity of symptoms and low quality of life, in particular in the "life outlook" dimension. The subtypes distribution was the following: 18.3% inattentive subtype, 8.3% hyperactive/impulsive subtype and 70% combined subtype. The hyperactive/impulsive subtype showed a significantly higher frequency in females, while the inattentive subtype was more frequent in males. Patients with the hyperactive/impulsive subtype showed worse quality of life and more frequent anxiety disorders. CONCLUSIONS: Considering the different clinical profiles among various subtypes, these data add relevance to subtypes classification of adult ADHD.