Medical comorbidities in bipolar disorder (BIPCOM): clinical validation of risk factors and biomarkers to improve prevention and treatment. Study protocol.

BACKGROUND: BIPCOM aims to (1) identify medical comorbidities in people with bipolar disorder (BD); (2) examine risk factors and clinical profiles of Medical Comorbidities (MC) in this clinical group, with a special focus on Metabolic Syndrome (MetS); (3) develop a Clinical Support Tool (CST) for the personalized management of BD and medical comorbidities. METHODS: The BIPCOM project aims to investigate MC, specifically MetS, in individuals with BD using various approaches. Initially, prevalence rates, characteristics, genetic and non-genetic risk factors, and the natural progression of MetS among individuals with BD will be assessed by analysing Nordic registers, biobanks, and existing patient datasets from 11 European recruiting centres across 5 countries. Subsequently, a clinical study involving 400 participants from these sites will be conducted to examine the clinical profiles and incidence of specific MetS risk factors over 1 year. Baseline assessments, 1-year follow-ups, biomarker analyses, and physical activity measurements with wearable biosensors, and focus groups will be performed. Using this comprehensive data, a CST will be developed to enhance the prevention, early detection, and personalized treatment of MC in BD, by incorporating clinical, biological, sex and genetic information. This protocol will highlight the study's methodology. DISCUSSION: BIPCOM's data collection will pave the way for tailored treatment and prevention approaches for individuals with BD. This approach has the potential to generate significant healthcare savings by preventing complications, hospitalizations, and emergency visits related to comorbidities and cardiovascular risks in BD. BIPCOM's data collection will enhance BD patient care through personalized strategies, resulting in improved quality of life and reduced costly interventions. The findings of the study will contribute to a better understanding of the relationship between medical comorbidities and BD, enabling accurate prediction and effective management of MetS and cardiovascular diseases. TRIAL REGISTRATION: ISRCTN68010602 at https://www.isrctn.com/ISRCTN68010602 . Registration date: 18/04/2023.

The relationship between obsessive-compulsive symptoms and real-life functioning in schizophrenia: New insights from the multicenter study of the Italian Network for Research on Psychoses.

BACKGROUND: Although obsessive-compulsive disorder (OCD) is highly prevalent in schizophrenia, its relationship with patients' real-life functioning is still controversial. METHODS: The present study aims at investigating the prevalence of OCD in a large cohort of non-preselected schizophrenia patients living in the community and verifying the relationship of OCD, as well as of other psychopathological symptoms, with real-life functioning along a continuum of OCD severity and after controlling for demographic variables. RESULTS: A sample of 327 outpatients with schizophrenia was enrolled in the study and collapsed into three subgroups according to OCD severity (subclinical, mild-moderate, severe). A series of structural equation modeling (SEM) was performed to analyze in each subgroup the association of obsessive-compulsive symptoms with real-life functioning, assessed through the Specific Levels of Functioning Scale and the UCSD Performance-Based Skills Assessment. Moreover, latent profile analysis (LPA) was performed to infer latent subpopulations. In the subclinical OCD group, obsessive-compulsive symptoms (OCS) were not associated with functioning, whereas in the mild-moderate OCD group, they showed a positive relationship, particularly in the domains of work and everyday life skills. The paucity of patients with severe OCD did not allow performing SEM analysis in this group. Finally, LPA confirmed a subgroup with mild-moderate OCS and more preserved levels of functioning. CONCLUSIONS: These findings hint at a positive association between mild-moderate OCD and real-life functioning in individuals with schizophrenia and encourage a careful assessment of OCD in personalized programs to sustain daily life activities.

Overcoming the barriers to identifying and managing treatment-resistant schizophrenia and to improving access to clozapine: A narrative review and recommendation for clinical practice.

Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia (TRS). Although a large body of evidence supports its efficacy and favorable risk-benefit ratio in individuals who have failed two or more antipsychotics, clozapine remains underused. However, variations in clozapine utilization across geographic and clinical settings suggest that it could be possible to improve its use. In this narrative review and expert opinion, we summarized information available in the literature on the mechanisms of action, effectiveness, and potential adverse events of clozapine. We identified barriers leading to discouragement in clozapine prescription internationally, and we proposed practical solutions to overcome each barrier. One of the main obstacles identified to the use of clozapine is the lack of appropriate training for physicians: we highlighted the need to develop specific professional programs to train clinicians, both practicing and in residency, on the relevance and efficacy of clozapine in TRS treatment, initiation, maintenance, and management of potential adverse events. This approach would facilitate physicians to identify eligible patients and offer clozapine as a treatment option in the early stage of the disease. We also noted that increasing awareness of the benefits of clozapine among healthcare professionals, people with TRS, and their caregivers can help promote the use of clozapine. Educational material, such as leaflets or videos, could be developed and distributed to achieve this goal. The information provided in this article may be useful to improve disease burden and support healthcare professionals, patients, and caregivers navigating the complex pathways to TRS management.

Worldwide prevalence of obsessive-compulsive symptoms during the COVID-19 pandemic: A systematic review and meta-analysis.

During the COVID-19 pandemic governments worldwide implemented contagion-containing measures (i.e., physical distancing, hand sanitizing, mask wearing and quarantine). The similarities between these measures and obsessive-compulsive phenomenology (e.g., contamination concerns and repetitive washing and/or checking) led to inquiries about the frequency with which obsessive-compulsive symptoms (OCS) were encountered during the COVID-19 pandemic. We conducted a systematic review and meta-analysis to ascertain the prevalence of OCS in individuals of any age during the pandemic (i.e., any obsessive-compulsive symptoms that are clinically significant as shown by a score above the cut-off score of a scale, without necessarily fulfilling the diagnostic threshold for a diagnosis of OCD). A systematic search of relevant databases identified 35 studies, which were included in the systematic review following our inclusion and exclusion criteria. Most of the studies were conducted in adults from the general population and adopted an online assessment method, with 32 studies being eligible for meta-analysis. The meta-analysis resulted in a 20% average prevalence of OCS during the pandemic, with very high heterogeneity among the included studies (I2 99.6%). The highest prevalence of OCS was found in pregnant women (36%, n = 5), followed by individuals diagnosed with COVID-19 (22%, n = 4) and general population (22%, n = 19), undergraduates (21%, n = 5), and healthcare workers (5%, n = 5). The prevalence rates of OCS were higher in Asia (26%, n = 17) and North America (25%, n = 3) than in Europe (13%, n = 12) and Africa (7%, n = 4). Among the studies included, rates appeared higher in certain countries, though this difference did not reach statistical significance and was limited by very few studies conducted in certain countries. When compared to pre-pandemic rates, there seemed to be higher rates of OCS during the COVID-19 pandemic in Asia, Europe, and pregnant women. These findings are discussed considering the impact of the pandemic and contagion-containing measures on the perception and reporting of OCS, and susceptibility of the vulnerable population groups to experiencing OCS during the pandemic.

Perspectives on the impact of vortioxetine on the treatment armamentarium of major depressive disorder.

INTRODUCTION: Major Depressive Disorder (MDD) is a mental health issue that significantly affects patients' quality of life and functioning. Despite available treatments, many patients continue to suffer due to incomplete symptom resolution and side effects. AREAS COVERED: This manuscript examines Vortioxetine's role in Major Depressive Disorder (MDD) treatment, highlighting its potential to reshape therapeutic strategies due to its unique Multimodal action and proven broad-spectrum efficacy in multiple depressive domains. A detailed examination of Vortioxetine's pharmacological aspects, including indications, dosage, pharmacodynamics, and pharmacokinetics, is provided, emphasizing its safety and effectiveness. The discussion extends to Vortioxetine's role in acute-phase treatment and maintenance of MDD and its profound impact on specialized depression domains. EXPERT OPINION: Vortioxetine is distinguished for its novel multimodal serotonin modulation mechanism, showcasing significant promise as an innovative treatment for MDD. Its efficacy, which is dose-dependent, along with a commendable tolerability profile, positions it as a potential leading option for initial treatment strategies. The discourse on dosage titration, particularly the strategy of initiating treatment at lower doses followed by gradual escalation, underscores the approach toward minimizing initial adverse effects while optimizing therapeutic outcomes, aligning with the principles of personalized medicine in psychiatric care.

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.

Membrane Permeation of Psychedelic Tryptamines by Dynamic Simulations.

Renewed scientific interest in psychedelic compounds represents one of the most promising avenues for addressing the current burden of mental health disorders. Classic psychedelics are a group of compounds that exhibit structural similarities to the naturally occurring neurotransmitter serotonin (5-HT). Acting on the 5-HT type 2A receptors (HT2ARs), psychedelics induce enduring neurophysiological changes that parallel their therapeutic psychological and behavioral effects. Recent preclinical evidence suggests that the ability of psychedelics to exert their action is determined by their ability to permeate the neuronal membrane to target a pool of intracellular 5-HT2ARs. In this computational study, we employ classical molecular dynamics simulations and umbrella sampling techniques to investigate the permeation behavior of 12 selected tryptamines and to characterize the interactions that drive the process. We aim at elucidating the impact of N-alkylation, indole ring substitution and positional modifications, and protonation on their membrane permeability. Dimethylation of the primary amine group and the introduction of a methoxy group at position 5 exhibited an increase in permeability. Moreover, there is a significant influence of positional substitutions on the indole groups, and the protonation of the molecules substantially increases the energy barrier at the center of the bilayer, making the compounds highly impermeable. All the information extracted from the trends predicted by the simulations can be applied in future drug design projects to develop psychedelics with enhanced activity.

Efficacy and safety of ketamine and esketamine for unipolar and bipolar depression: an overview of systematic reviews with meta-analysis.

Background: Unipolar and bipolar depression present treatment challenges, with patients sometimes showing limited or no response to standard medications. Ketamine and its enantiomer, esketamine, offer promising alternative treatments that can quickly relieve suicidal thoughts. This Overview of Reviews (OoR) analyzed and synthesized systematic reviews (SRs) with meta-analysis on randomized clinical trials (RCTs) involving ketamine in various formulations (intravenous, intramuscular, intranasal, subcutaneous) for patients with unipolar or bipolar depression. We evaluated the efficacy and safety of ketamine and esketamine in treating major depressive episodes across various forms, including unipolar, bipolar, treatment-resistant, and non-resistant depression, in patient populations with and without suicidal ideation, aiming to comprehensively assess their therapeutic potential and safety profile. Methods: Following PRIOR guidelines, this OoR's protocol was registered on Implasy (ID:202150049). Searches in PubMed, Scopus, Cochrane Library, and Epistemonikos focused on English-language meta-analyses of RCTs of ketamine or esketamine, as monotherapy or add-on, evaluating outcomes like suicide risk, depressive symptoms, relapse, response rates, and side effects. We included studies involving both suicidal and non-suicidal patients; all routes and formulations of administration (intravenous, intramuscular, intranasal) were considered, as well as all available comparisons with control interventions. We excluded meta-analysis in which the intervention was used as anesthesia for electroconvulsive therapy or with a randomized ascending dose design. The selection, data extraction, and quality assessment of studies were carried out by pairs of reviewers in a blinded manner. Data on efficacy, acceptability, and tolerability were extracted. Results: Our analysis included 26 SRs and 44 RCTs, with 3,316 subjects. The intervention is effective and well-tolerated, although the quality of the included SRs and original studies is poor, resulting in low certainty of evidence. Limitations: This study is limited by poor-quality SRs and original studies, resulting in low certainty of the evidence. Additionally, insufficient available data prevents differentiation between the effects of ketamine and esketamine in unipolar and bipolar depression. Conclusion: While ketamine and esketamine show promising therapeutic potential, the current evidence suffers from low study quality. Enhanced methodological rigor in future research will allow for a more informed application of these interventions within the treatment guidelines for unipolar and bipolar depression. Systematic review registration: [https://inplasy.com/inplasy-2021-5-0049/], identifier (INPLASY202150049).

Clinical benefits and bioequivalence of vortioxetine oral drop solution versus oral tablets.

BACKGROUND: Vortioxetine is efficacious and well tolerated in patients with major depressive disorder (MDD) and is available as an immediate-release tablet and oral drop solution. The oral drop solution may offer clinical benefits versus a tablet, such as the reduced risk of nausea, personalised dosing and ease of administration. AIMS: To investigate the bioequivalence of vortioxetine 20 mg/mL oral drop solution versus a 20 mg immediate-release tablet. METHODS: Healthy adults were randomised 1:1 to receive vortioxetine 20 mg oral drop solution or immediate-release 20 mg tablet after fasting on days 1 and 29 in an open-label, single-centre, single-dose crossover study. The area under the plasma concentration-time curve from 0 to 72 h (AUC0-72h) and maximum plasma concentration (Cmax) were analysed. Bioequivalence was concluded if the 90% CI for the oral drop solution-to-immediate-release tablet ratio for AUC0-72h and Cmax were contained within a range of 0.80-1.25. RESULTS: Vortioxetine oral drop solution was bioequivalent to the tablet (n = 26; estimated AUC0-72h ratio 1.06 (90% CI: 1.03-1.10); Cmax ratio 1.01 (90% CI: 0.97-1.05)). A similar proportion of participants reported adverse events in each study arm but more headache events (7 vs 1) were reported with the oral drop solution versus tablet. The most common adverse event was nausea (16-23% of participants; all mild intensity). CONCLUSIONS: Vortioxetine oral drop solution is bioequivalent to immediate-release tablets. Oral drop solution provides an alternative to tablets and facilitates clinical benefit through individualised treatment, including gradual dose up-titration, for patients with MDD.

The impact of COVID-19 pandemic in patients with a diagnosis of Oral Lichen Planus: Pain perception and psychological profile analysis.

OBJECTIVES: To assess the impact of COVID-19 in patients affected by OLP, in terms of level of pain, stress, depression and anxiety and their impact on the clinical manifestation of the disease. MATERIAL AND METHODS: A longitudinal design was employed. Psychometric evaluations of anxiety, stress, and depression were conducted using the DASS21 scale, while pain levels were measured using the VAS scale. Clinical diagnosis and phenotype evaluation were performed. RESULTS: The study included 24 patients with an average age of 62.9 years, with 70.8% presenting erosive OLP. Results revealed a significant worsening of anxiety, stress, and depression scores during the pandemic. Pain level (1.5 ± 1.2 pre-pandemic VS 3.8 ± 1.1 during the pandemic, p < 0.0001) was also negatively affected. CONCLUSIONS: These findings highlight the potential interplay between psychological stress and oral health conditions, emphasizing the need for a comprehensive understanding of OLP's complex etiology and its response to external stressors. CLINICAL RELEVANCE: Multidisciplinary care strategies to address both physical and psychological aspects of OLP patients is recommended following the present findings. Further research is warranted to confirm these observations in larger multicenter studies and to guide tailored guidance approaches for OLP patients during challenging times.

Trazodone in the Management of Major Depression Among Elderly Patients with Dementia: A Narrative Review and Clinical Insights.

Objective: Major depressive disorder (MDD) often co-occurs with dementia and other neurological disorders, and treatment with antidepressants can improve symptoms, quality of life, and survival in these patients. This narrative review provides an expert opinion about the role and effectiveness of trazodone in the treatment of older adults with MDD and cognitive impairment due to physical illnesses, such as dementia. Results: Because of its mechanism of action, trazodone can treat several depression symptoms often seen in people with dementia, including insomnia, agitation, anxiety, cognitive impairment, and irritability. Conclusion: Trazodone may be beneficial for patients with dementia or other neurological disorders comorbid with MDD, especially when the clinical picture of depression includes or is comorbid to symptoms of insomnia, irritability, inner tension, anxiety, or psychomotor agitation.

Is intravenous valproate more efficacious than oral valproate for inpatients with bipolar I disorder with a manic or depressive episode and concomitant symptoms of opposite polarity?

INTRO: Valproic acid (VPA) is a commonly prescribed mood stabilizer, available in both oral (OS) and intravenous (IV) formulations. However, few studies have compared their safety and efficacy. This retrospective study aimed to investigate the safety and efficacy of and IV-VPA in patients with Bipolar Disorder. METHODS: Fifty patients with Bipolar Disorder experiencing a manic or depressive episode, with concomitant symptoms of opposite polarity, admitted to our inpatient unit and treated with IV-VPA were included in a retrospective, single-centre, non-randomized, open-label, parallel-group comparative study. Fifty patients experiencing a manic or depressive episode, with concomitant symptoms of opposite polarity, treated with oral-VPA and selected among those who were admitted to the inpatient unit prior to the introduction of IV-VPA in our clinical practice, were included as the control group (matched based on age, gender and clinical scales score at baseline). The Clinical Global Impression (CGI), Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) scores were recorded at baseline, after 3 days of treatment and discharge from the inpatient unit. Patients were asked to respond on the basis of the symptoms present on the day the scale was administered. Response rate and the presence of adverse effects were also recorded. RESULTS: Both patients treated with oral and IV-VPA demonstrated significant improvements in all psychometric scales (p < 0.001). However, the IV group exhibited superior efficacy, with significantly lower scores on the CGI, YMRS, MADRS and HAM-A scales on Day 3 and at discharge from the inpatient unit. The IV-VPA treatment showed higher response rates on all psychometric scales, and no adverse effects were reported in either group. CONCLUSION: This retrospective study supports the use of IV-VPA as a more efficacious treatment option for patients with Bipolar Disorder, particularly in acute settings where rapid symptom improvement is crucial. Both oral and IV-VPA were found to be safe and well-tolerated.

["Insomnia disorder": an overview of current models and of the complex link with psychopathology.] / Il "disturbo da insonnia": una overview sui modelli attuali e sul complesso link con i quadri psicopatologici.

Insomnia disorder is the most common sleep disorder. The new models frame insomnia as a stress-related disorder and a "24-hour" syndrome with night and day symptoms. The hyperarousal has been identified as the neurobiological mechanism underlying chronic insomnia. Since chronic insomnia is considered a risk factor for psychopathology it is possible that hyperarousal may act as a link with psychopathological conditions. Assessing and treating insomnia could therefore also have a preventive value in psychopathology.

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.

Nationwide consensus on the clinical management of treatment-resistant depression in Italy: a Delphi panel.

BACKGROUND: Treatment-resistant depression (TRD) is defined by the European Medicines Agency as a lack of clinically meaningful improvement after treatment, with at least two different antidepressants. Individual, familiar, and socio-economic burden of TRD is huge. Given the lack of clear guidelines, the large variability of TRD approaches across different countries and the availability of new medications to meet the need of effective and rapid acting therapeutic strategies, it is important to understand the consensus regarding the clinical characteristics and treatment pathways of patients with TRD in Italian routine clinical practice, particularly in view of the recent availability of esketamine nasal spray. METHODS: A Delphi questionnaire with 17 statements (with a 7 points Likert scale for agreement) was administered via a customized web-based platform to Italian psychiatrists with at least 5 years of experience and specific expertise in the field of depression. In the second-round physicians were asked to answer the same statements considering the interquartile range of each question as an index of their colleagues' responses. Stata 16.1 software was used for the analyses. RESULTS: Sixty panellists, representative of the Italian territory, answered the questionnaire at the first round. For 8/17 statements more than 75% of panellists reached agreement and a high consensus as they assigned similar scores; for 4 statements the panellists assigned similar scores but in the middle of the Likert scale showing a moderate agreement with the statement, while for 5 statements there was indecision in the agreement and low consensus with the statement. CONCLUSIONS: This Delphi Panel showed that there is a wide heterogeneity in Italy in the management of TRD patients, and a compelling need of standardised strategies and treatments specifically approved for TRD. A high level of consensus and agreement was obtained about the importance of adding lithium and/or antipsychotics as augmentation therapies and in the meantime about the need for long-term maintenance therapy. A high level of consensus and agreement was equally reached for the identification of esketamine nasal spray as the best option for TRD patients and for the possibility to administrate without difficulties esketamine in a community outpatient setting, highlighting the benefit of an appropriate educational support for patients.

Role of trazodone in treatment of major depressive disorder: an update.

Major depressive disorder (MDD) is the most common mood disorder and a leading cause of disability worldwide. Trazodone, a triazolopyridine serotonin receptor antagonist and reuptake inhibitor (SARI) antidepressant approved for major depressive disorder (MDD) in adults, has established efficacy that is comparable to other available antidepressants, and is effective for a range of depression symptoms, including insomnia, which is one of the most common and bothersome symptoms of depression. Also, trazodone's pharmacodynamic properties allow it to avoid the side effects of insomnia, anxiety and sexual dysfunction often associated with selective serotonin reuptake inhibitor antidepressants. In this narrative review, we have summarized recent clinical trials and real-world data on trazodone, including the recently introduced once-daily formulation, which has single dose pharmacokinetic properties that maintain effective blood trazodone levels for 24 h, while avoiding concentration peaks associated with side effects. This, combined with a low incidence of weight gain, and sexual dysfunction, may improve adherence to treatment. The most common adverse effects of trazodone are somnolence, headache, dizziness and xerostomia. It has minimal anticholinergic activity but may be associated infrequently with orthostatic hypotension (especially in patients with cardiovascular disease or older adults), QT interval prolongation, cardiac arrhythmias, and rare episodes of priapism. The low liability for activating side effects, the efficacy on symptoms such as insomnia and psychomotor agitation and the rapid onset of action make it useful for many depressed patients, both in monotherapy at nominal dosages of 150-300 mg/day, and in combination with other antidepressants at lower dosages.

Exploring depression in Alzheimer's disease: an Italian Delphi Consensus on phenomenology, diagnosis, and management.

BACKGROUND: In Alzheimer's disease (AD), the progressive cognitive impairment is often combined with a variety of neuropsychiatric symptoms, firstly depression. Nevertheless, its diagnosis and management is difficult, since specific diagnostic criteria and guidelines for treatment are still lacking. The aim of this Delphi study is to reach a shared point of view among different Italian specialists on depression in AD. METHODS: An online Delphi survey with 30 questions regarding epidemiology, diagnosis, clinical features, and treatment of depression in AD was administered anonymously to a panel of 53 expert clinicians. RESULTS: Consensus was achieved in most cases (86%). In the 80% of statements, a positive consensus was reached, while in 6% a negative consensus was achieved. No consensus was obtained in 14%. Among the most relevant findings, the link between depression and AD is believed to be strong and concerns etiopathogenesis and phenomenology. Further, depression in AD seems to have specific features compared to major depressive disorder (MDD). Regarding diagnosis, the DSM 5 diagnostic criteria for MDD seems to be not able to detect the specific aspects of depression in AD. Concerning treatment, antidepressant drugs are generally considered the main option for depression in dementia, according to previous guidelines. In order to limit side effects, multimodal and SSRI antidepressant are preferred by clinicians. In particular, the procognitive effect of vortioxetine seems to be appealing for the treatment of depression in AD. CONCLUSIONS: This study highlights some crucial aspects of depression in AD, but more investigations and specific recommendations are needed.

Moving from serotonin to serotonin-norepinephrine enhancement with increasing venlafaxine dose: clinical implications and strategies for a successful outcome in major depressive disorder.

INTRODUCTION: Mental health disorders, especially depressive and anxiety disorders, are associated with substantial health-related burden. While the second-generation antidepressants are widely accepted as first-line pharmacological treatment for major depressive disorder (MDD), patient response to such treatment is variable, with more than half failing to achieve complete remission, and residual symptoms are frequently present. AREAS COVERED: Here, the pharmacodynamics of venlafaxine XR are reviewed in relation to its role as both a selective serotonin reuptake inhibitor (SSRI) and a serotonin-norepinephrine-reuptake inhibitor (SNRI), and we look at how these pharmacodynamic properties can be harnessed to guide clinical practice, asking the question 'is it possible to develop a symptom-cluster-based approach to the treatment of MDD with comorbid anxiety utilizing venlafaxine XR?.' Additionally, three illustrative clinical cases provide practical examples of the utility of venlafaxine-XR in real-world clinical practice. The place of venlafaxine XR in managing fatigue/low energy, a frequent residual symptom in MDD, is explored using pooled data from clinical trials of venlafaxine XR. EXPERT OPINION: Venlafaxine XR should be considered as a first-line treatment for MDD with or without comorbid anxiety, and there are clear pharmacodynamic signals supporting a symptom cluster-based treatment paradigm for venlafaxine XR.

Autistic traits distribution in different psychiatric conditions: A cluster analysis on the basis of the Adult Autism Subthreshold Spectrum (AdAS Spectrum) questionnaire.

Increasing interest is being paid on full-threshold and sub-threshold autism spectrum conditions among adults. Sub-threshold autistic traits (AT) seem to be distributed in a continuum from the clinical to the general population, being particularly higher among subjects with other psychiatric disorders. The aim of the present study was to evaluate the distribution of AT in a sample of subjects with different psychiatric conditions by means of a cluster analysis on the basis of the score reported to the AdAS Spectrum instrument. A total of 738 subjects recruited by seven Italian Universities were divided in 5 groups depending on the clinical diagnosis: Autism spectrum disorder (ASD), subthreshold ASD symptoms (partial ASD), Bipolar disorder (BD), Feeding and eating disorders (FED), and controls (CTLs). All subjects were assessed with the AdAS Spectrum. The cluster analysis identified 3 clusters: the high, medium and low autism clusters. The Restricted interests and rumination domain reported the highest influence in forming the clusters. The high, medium and low autism clusters were respectively more represented in the ASD, partial ASD and CTL groups. The clusters were represented intermediately in the FED and BD groups, confirming the presence of intermediate levels of AT in these clinical populations.