Prevalence and Correlates of Serotonin Syndrome in Real-World Inpatients.

BACKGROUND: Serotonin syndrome (SS) is a potentially life-threatening adverse drug reaction due to an increased central and peripheral serotonin activity, which usually presents as a triad of behavioral changes, neuromuscular excitability, and autonomic instability. Probably SS is often misdiagnosed, and its symptoms are mistaken for psychiatric symptoms or general medical issues: the true incidence of SS is not clear, and literature concerning potential risk factors is scarce. Our aims were to examine the prevalence of SS in a naturalistic sample of hospitalized patients and to evaluate potential factors related to the risk of developing the condition. METHODS: The sample included 133 patients being treated with serotonergic medications admitted to the psychiatric inpatient unit of the San Luigi Gonzaga Hospital. All patients received a medical examination (including a neurological examination) within 24 hours of admission. Serotonin syndrome was diagnosed according to Hunter Criteria. RESULTS: Sixteen patients (12%) were diagnosed with SS. In the subgroup of subjects with SS, we found a higher rate of male patients when compared with subjects with no SS (62.5% vs 33.3%, P = 0.023). CONCLUSIONS: SS probably is an underestimated condition, which should be carefully assessed in patients on serotonergic medications. Male gender was the only factor found to be significantly related to a higher risk of developing SS. Further studies on larger samples are needed, to gain more information on possible risk factors and to identify subjects more prone to developing SS, given the potential risk for patients' health.

The Resurgence of Exogenous Psychosis: A Phenomenological Examination of Substance-Induced Psychopathology.

ABSTRACT: The psychopathological manifestations associated with substance use, including induced psychotic experiences, are increasingly relevant but not well-understood within the medical community. Novel psychoactive substances and potentiated old compounds like cannabis and cocaine have emerged as a global concern, especially among adolescents and young adults. Transition rates from substance-induced psychosis (SIP) to persistent psychosis are significant, particularly in cases of cannabis-induced psychosis. Scientific inquiry into induced psychotic phenomena has revealed differences between SIP and primary psychotic disorders, highlighting the risk factors associated with each. The concept of exogenous psychosis, including its toxic variant known as lysergic psychoma, provides valuable insights into the role of external factors in psychosis development. A phenomenological approach characterizes this disruption in perception as a shift in temporal and spatial dimensions, leading to auditory and visual hallucinations. The "twilight state" of consciousness plays a crucial role in the transition from substance use to psychosis, with implications for spatiality, intersubjectivity, and temporality. This complex path to psychosis challenges traditional diagnostic models and underscores the need for a more nuanced understanding of substance-induced psychopathological experiences.

The Loss of Spatiality and Temporality in Twilight Consciousness: The Emergence of Exogenous Psychosis Induced by Novel Psychoactive Substances.

BACKGROUND: The state of twilight consciousness is marked by a focused narrowing of awareness, maintaining vigilance and attention while simultaneously experiencing perceptual shifts in the surrounding environment. It is crucial to recognize that this twilight state represents not just a contraction but also an expansion of conscious experience. SUMMARY: Substances of abuse, particularly new psychoactive substances, play a significant role in inducing this twilight state. They achieve this by deconstructing essential components of consciousness, such as the perception of time and space. KEY MESSAGE: This paper aimed to explore the phenomenon of the twilight state of consciousness and shed light on how new psychoactive substances can alter the perception of time and space during this twilight phase, potentially triggering exogenous psychosis. This comprehensive inquiry employs a phenomenological approach to the study of consciousness, recognizing it as the primary tool for ascribing significance to this intricate yet often overlooked aspect of psychopathology.

Assessing suicidality in adult ADHD patients: prevalence and related factors : Suicidality in adult ADHD patients.

BACKGROUND: The association between Attention-deficit hyperactivity disorder (ADHD) and suicidality has been subject of growing interest for research in the latest years. Suicidality was generally assessed categorically and without the use of validated instruments, leading to heterogeneous or even conflicting evidence. The prevalence of both suicidal ideation and attempts varies considerably, and the associated risk factors remain unclear. Our study investigated suicidality in ADHD using a dimensional approach and a validated and internationally recognized instrument. Our primary aim was to evaluate the prevalence of suicidal ideation (SI), severe suicidal ideation (SSI), suicidal behavior (SB) and non suicidal self-injury behavior (NSSIB) in a sample of adult patients with ADHD. The second objective was to identify sociodemographic and clinical features associated with increased risk of suicidality in these patients. METHODS: The sample included 74 adult patients with clinical diagnosis of ADHD. Suicidality was assessed by administering the Columbia-Suicide Severity Rating Scale. Logistic regressions were used to examine predictors of SI, SSI, SB and NSSIB. RESULTS: The lifetime prevalence of SI and SSI were 59.5% and 16.2%, respectively. The 9.5% of patients showed lifetime SB, while NSSIB was found in 10.8% of the subjects. Lifetime SI was associated with severity of inattentive symptoms during adulthood, low self-esteem and impairment in social functioning. Lifetime SSI appeared related to severity of inattentive symptoms during childhood, attentional impulsiveness and number of hospitalizations, while physical activity appeared to be protective. The prevalence of lifetime SB and NSSIB did not appear significantly related to any socio-demographic or clinical feature. CONCLUSIONS: Adults with ADHD should be considered at risk of suicide and it is important to determine which patients are at higher risk, in order to guide preventive interventions. The association between ADHD and suicidal ideation did not appear to be influenced by psychiatric comorbidities, but rather by inattention itself, which represents the core symptom of ADHD.

Risk Factors for Suicide Reattempt among Adolescents and Young Adults: The Role of Psychiatric Disorders.

Suicidal behaviour among young people is a serious public health concern. Each suicide attempt is related to further suicide attempts and completed suicide. This study aims to explore risk factors associated with repeated suicide attempt among adolescents and young adults. The cohort included 510 patients aged 12-29 years residing in Piedmont Region in North-Western Italy, who had been admitted to hospital or emergency department with a diagnosis of suicide attempt between 2010 and 2020. Cox regression models were used to evaluate potential risk factors for repeated suicide attempt. During the 11-years follow-up, 20.6% of adolescents and young adults repeated suicide attempt, 24.8% of females and 12.3% of males. Nearly 90% of youth who attempted suicide had a diagnosis of psychiatric disorder. After adjustment, younger age of onset of suicidal behaviour, and diagnosis of schizophrenia, bipolar disorder, depressive disorder, anorexia nervosa and personality disorder were significantly associated with repeated suicide attempt. The early identification of patients at higher risk of repetition of suicidal behaviour is of crucial importance. Better understanding of risk factors and effective treatment of mental disorders could help suicide prevention to reduce the burden of the problem among young people. Special attention should be paid during the initial months following discharge from hospital or emergency department, when suicide reattempt risk is very high.

Effects of seasonality in emergency admissions for mental disorders: two years of clinical experience.

OBJECTIVES: This retrospective study, conducted in Turin, Italy, between January 2021 and February 2023, investigates the impact of seasonal heatwaves on emergency department (ED) admissions for mental disorders. METHODS: Through the analysis of data from 2,854 patients, this research found a significant link between the occurrence of heatwaves, especially from June to August, and an elevated rate of ED admissions for psychiatric conditions. RESULTS: The data indicate a clear seasonal pattern, with admissions peaking during the hot months and diminishing in the colder months. Particularly, the study delineates an enhanced correlation between heatwaves and admissions for severe psychiatric disorders, such as bipolar disorder, major depression, personality disorders, and schizophrenia, accounting for 1,868 of the cases examined. This correlation was most pronounced among individuals aged 50-59 years. CONCLUSIONS: The results of this study highlight a critical association between the incidence of seasonal heatwaves and an uptick in ED visits for psychiatric disorders, with a distinct impact on severe cases. It underscores the urgency for healthcare systems to anticipate seasonal fluctuations in psychiatric ED admissions and to allocate resources effectively to support patients during peak periods.

Which patients benefit from adding short-term psychodynamic psychotherapy to antidepressants in the treatment of depression? A systematic review and meta-analysis of individual participant data.

BACKGROUND: Adding short-term psychodynamic psychotherapy (STPP) to antidepressants increases treatment efficacy, but it is unclear which patients benefit specifically. This study examined efficacy moderators of combined treatment (STPP + antidepressants) v. antidepressants for adults with depression. METHODS: For this systematic review and meta-analysis (PROSPERO registration number: CRD42017056029), we searched PubMed, PsycINFO, Embase.com, and the Cochrane Library from inception to 1 January 2022. We included randomized clinical trials comparing combined treatment (antidepressants + individual outpatient STPP) v. antidepressants in the acute-phase treatment of depression in adults. Individual participant data were requested and analyzed combinedly using mixed-effects models (adding Cochrane risk of bias items as covariates) and an exploratory machine learning technique. The primary outcome was post-treatment depression symptom level. RESULTS: Data were obtained for all seven trials identified (100%, n = 482, combined: n = 238, antidepressants: n = 244). Adding STPP to antidepressants was more efficacious for patients with high rather than low baseline depression levels [B = -0.49, 95% confidence interval (CI) -0.61 to -0.37, p < 0.0001] and for patients with a depressive episode duration of >2 years rather than <1 year (B = -0.68, 95% CI -1.31 to -0.05, p = 0.03) and than 1-2 years (B = -0.86, 95% CI -1.66 to -0.06, p = 0.04). Heterogeneity was low. Effects were replicated in analyses controlling for risk of bias. CONCLUSIONS: To our knowledge, this is the first study that examines moderators across trials assessing the addition of STPP to antidepressants. These findings need validation but suggest that depression severity and episode duration are factors to consider when adding STPP to antidepressants and might contribute to personalizing treatment selection for depression.

Two-Injection Start Regimen of Long-Acting Aripiprazole in 133 Patients With Schizophrenia.

PURPOSE/BACKGROUND: Based on a population-pharmacokinetic model, the European Medicines Agency has recently approved a simplified starting strategy of aripiprazole once a month (AOM), injectable and long-acting antipsychotic, with two 400 mg injections and a single oral 20 mg dose of aripiprazole, administered on the same day, instead of 1 injection and 14 daily administrations of concurrent oral aripiprazole. However, to our knowledge, no previous study has reported the safety and tolerability of this regimen in real-world patients. METHODS/PROCEDURES: We retrospectively reviewed medical records of 133 patients who received the newly approved 2-injection start regimen as part of their standard care in 10 Italian clinical centers. FINDINGS/RESULTS: Adverse effects were mild or moderate, with no clinically evident difference from the adverse effects observed in previous trials where AOM was started with a single injection followed by 14 days of orally administered aripiprazole. None of the patients who started AOM after the 2-injection start regimen experienced severe adverse effects or severe adverse effects. IMPLICATIONS/CONCLUSIONS: The coadministration of 2 injections of 400 mg aripiprazole and 20 mg oral aripiprazole was not associated with safety concerns beyond those reported after a single injection followed by 14 days of orally administered aripiprazole. Our results should be interpreted with caution, due to the limited sample size and to the retrospective design of the study.

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment-resistant depression.

BACKGROUND: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD. OBJECTIVES: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch. METHODS: Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up. RESULTS: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch. CONCLUSIONS: Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment.

Risk factors for mortality after hospitalization for suicide attempt: results of 11-year follow-up study in Piedmont Region, Italy.

PURPOSE: Suicide attempters are at high risk of premature death, both for suicide and for non-suicidal causes. The aim of this study is to investigate risk factors and temporal span for mortality in a cohort of cases admitted to hospital for suicide attempt. METHODS: The cohort included 1489 patients resident in Piedmont Region, North West of Italy, who had been admitted to hospital or emergency department for suicide attempt between 2010 and 2020. Cox regression models were used to identify risk factors for death. The final multivariate model included gender, age, area deprivation index, family composition, psychiatric disorders, malignant neoplasms, neurological disorders, diabetes mellitus, cardiovascular diseases, chronic obstructive pulmonary disease, and intracranial injury or skull fracture. RESULTS: During the observation period, 7.3% of patients died. The highest mortality was observed within the first 12 months after suicide attempt, and remained elevated for many years afterwards. Male gender, older age, high deprivation index of the census area, single-parent family, mood disorders, malignant neoplasms, diabetes mellitus and intracranial injuries or skull fracture were independent predictors of death. Risk factors for natural and unnatural causes of death were also identified. CONCLUSIONS: The mortality risk of suicide attempters is very high, both in the months immediately following the attempt and afterwards. The identification of high-risk groups can help to plan outpatient care following the hospital discharge. Our findings urge the need to design strategies for the assistance and care of these patients at long term in order to reduce the unfavourable outcomes.

Dissociation and Temporality in Substance Abuse: A Clinical Phenomenological Overview.

The term "dissociation" encompasses a wide array of symptoms and phenomena, all sharing the common characteristic of involving altered states of consciousness where an individual temporarily loses the sense of continuity of their own identity. In the context of addiction pathology, however, the dissociative paradigm remains a topic of ongoing debate. It fluctuates between the description of individual dissociative symptoms and the notion of post-traumatic dissociation as a structural process. This process involves fragmentation that extends beyond the confines of perception and experience within a singular moment, instead ensuring a persistent discontinuity of the self throughout one's existence. Pathological addiction stresses the question of the donation of sense in this deep and dramatic experience; it situates individuals within a compressed and constricted realm of vital space, alongside a frozen perception of time. Within this context, every emotion, sensation, and comprehension becomes impaired. Consequently, we have embarked on a journey starting with a historical analysis: the aim was to construct an elucidative framework for the dissociative paradigm in the context of addiction. This involves an in-depth exploration of the fundamental constructs of trauma and temporality, examined through the lens of phenomenological perspective.

Achieving long-term goals through early personalized management of schizophrenia: expert opinion on the role of a new fast-onset long-acting injectable antipsychotic.

Definition of an appropriate and personalized treatment plan focused on long-term outcomes is crucial in the management of schizophrenia. Following review of the literature, a panel of six leading psychiatrists discussed the importance of clear and shared long-term goals when initiating antipsychotic treatment in light of their clinical experience. The importance of establishing shared and progressive treatment objectives was stressed, which should be tailored based on the patient's characteristics, goals, and preferences. Consensus emerged on the key role that therapeutic alliance and patient empowerment play throughout the course of treatment. Reduction in symptoms in the acute phase along with good efficacy and tolerability in the maintenance phase emerged as essential features of a therapy that can favor achievement of long-term outcomes. Long-acting injectable (LAI) antipsychotics enhance adherence to treatment compared to oral formulations and have been shown to be effective in the maintenance phase. Currently available LAIs are characterized by a delayed onset of action and require a loading dose or oral supplementation to achieve therapeutic concentrations. Risperidone ISM® is a novel LAI antipsychotic with fast and sustained release of antipsychotic, reaching therapeutic plasma levels within a few hours after administration without oral supplementation or loading doses. Risperidone ISM® has been shown to rapidly control symptoms in patients with an acute exacerbation of schizophrenia and to be effective and well tolerated as maintenance treatment irrespective of the severity of initial symptoms. It thus represents a valuable and novel therapeutic option in management of schizophrenia.

Correlates of long duration of untreated illness (DUI) in patients with bipolar disorder: results of an observational study.

BACKGROUND: Despite a high number of studies investigating the correlation between long Duration of Untreated Illness (DUI) and poor course of Bipolar Disorder (BD), the results concerning the impact of DUI on some specific factors, such as suicidality and medical comorbidities, are still inconsistent. This cross-sectional observational study aimed at analyzing potential socio-demographic and clinical correlates of long DUI in a large cohort of real-world, well-characterized BD patients. METHODS: The socio-demographic and clinical characteristics of 897 patients with BD were collected. The sample was divided for analysis in two groups (short DUI vs long DUI) according to a DUI cutoff of 2 years. Comparisons were performed using χ2 tests for categorical variables and the Kruskal-Wallis test for continuous variables. Logistic regression (LogReg) was used to identify explanatory variables associated with DUI (dependent variable). RESULTS: Six-hundred and sixty patients (75.5%) presented long DUI (> 2 years) and mean DUI was 15.7 years. The LogReg analysis confirmed the association of long DUI with bipolar II disorder (p: 0.016), lower age at onset (p < 0.001), depressive predominant polarity (p: 0.018), depressive polarity onset (p < 0.001), longer duration of illness (p < 0.001), lifetime suicide attempts (p: 0.045) and current medical comorbidities (p: 0.019). CONCLUSIONS: The present study confirms the association between long DUI and higher risk of suicide attempts in patients with BD. Moreover, an association between long DUI and higher rates of medical conditions has been found.

Facts and myths about the use of lithium for bipolar disorder in routine clinical practice: an expert consensus paper.

BACKGROUND: Bipolar disorder is one of the most burdensome severe mental disorders, characterized by high levels of personal and social disability. Patients often need an integrated pharmacological and non-pharmacological approach. Lithium is one of the most effective treatments available not only in psychiatry, but in the whole medicine, and its clinical efficacy is superior to that of other mood stabilizers. However, a declining trend on lithium prescriptions has been observed worldwide in the last 20 years, supporting the notion that lithium is a 'forgotten drug' and highlighting that the majority of patients with bipolar disorder are missing out the best available pharmacological option. Based on such premises, a narrative review has been carried out on the most common "misconceptions" and "stereotypes" associated with lithium treatment; we also provide a list of "good reasons" for using lithium in ordinary clinical practice to overcome those false myths. MAIN TEXT: A narrative search of the available literature has been performed entering the following keywords: "bipolar disorder", "lithium", "myth", "mythology", "pharmacological treatment", and "misunderstanding". The most common false myths have been critically revised and the following statements have been proposed: (1) Lithium should represent the first choice for the treatment of patients with bipolar disorder; (2) lithium treatment is effective in different patients' groups suffering from bipolar disorder; (3) Drug-drug interaction risk can be easily managed during lithium treatment; (4) The optimal management of lithium treatment includes periodical laboratory tests; (5) Slow-release lithium formulation has advantages compared to immediate release formulation; (6) Lithium treatment has antisuicidal properties; (7) Lithium can be carefully managed during pregnancy. CONCLUSIONS: In recent years, a discrepancy between evidence-based recommendations and clinical practice in using lithium treatment for patients with bipolar disorder has been highlighted. It is time to disseminate clear and unbiased information on the clinical efficacy, effectiveness, tolerability and easiness to use of lithium treatment in patients with bipolar disorder. It is necessary to reinvigorate the clinical and academic discussion about the efficacy of lithium, to counteract the decreasing prescription trend of one of the most effective drugs available in the whole medicine.

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.

Episodic obsessive-compulsive disorder and bipolar spectrum disorder: new evidence from a large Italian OCD sample.

OBJECTIVES: Obsessive-Compulsive Disorder (OCD) has been considered to be a chronic illness; however, some authors described a subtype of OCD characterised by symptom-free periods of time: Episodic-OCD (E-OCD). Only few studies focussed on this subtype of the disorder. The objectives of this research were to study the association between the episodic course of the disorder and lifetime psychiatric comorbidities and to investigate socio-demographic and other clinical features correlated to the episodic course. METHODS: The sample is composed of adult OCD patients. The course was defined episodic when at least one circumscribed symptom-free interval of at least 6 months was present. The sample was divided into two subgroups: Episodic-OCD and Chronic-OCD. Differences between groups were analysed with Student's t-test, χ2 tests, Fisher test and multivariate logistic regression. RESULTS: Data regarding 585 individuals were collected. 14.2% (N = 83) of our sample had an episodic course. Bipolar I comorbid disorder, abrupt onset, lower severity of illness and lower rates of repeating compulsions were associated with the likelihood of having an E-OCD. CONCLUSIONS: Our findings confirm that a significant proportion of OCD patients have an episodic course and that E-OCD could represent a specific endophenotype.

A significant proportion of OCD patients has an episodic course;Episodic OCD was related to comorbid Bipolar I Disorder;Episodic course was associated with an abrupt onset of OCD;Lower rates of repeating compulsions were associated with Episodic OCD.

CANNABIS USE AND SUICIDE IN NON-AFFECTIVE PSYCHOSIS: A MINI-REVIEW OF RECENT LITERATURE.

Proof of correlation between psychotic spectrum disorders and suicide are found in literature, as well as between cannabis use disorder (CUD) and suicide and between CUD and schizophrenia. The study population of the selected papers consists of subjects diagnosed with schizophrenia spectrum or cannabis or SCs induced psychosis. Our objective is to assess how suicide risk (defined as suicidal ideation/attempt or death by suicide) in this population may vary with exposure to cannabis or one of its main active compounds. We searched PubMed, Scopus and Psycinfo database from January 2010 to February 2022. Study designs of the included articles are distributed as follows: 6 cross-sectional studies, 3 cohort studies, 1 case-control studies, 1 randomized double-blind study, 1 case report. Selected cohort studies seem to agree in identifying an increased suicide risk in patients with schizophrenia spectrum disorders when exposed to cannabis use. The case-control study and selected cross-sectionals provide contradictory data. However, qualitative analysis seem to point toward a positive correlation between cannabis use and increased suicidal risk in patients with schizophrenia spectrum disorders. In conclusion, emerging data on the correlation between cannabis use and suicide risk in patients with schizophrenia or other schizophrenic spectrum disorders are insufficient to draw firm conclusions. Nonetheless these studies seem to suggest a positive correlation of cannabis use with increased suicide risk, particularly regarding first episode psychosis (FEP) and male gender. Clinicians should be aware of the possibility of a higher risk of suicidal behavior associated specifically with cannabis use for men and patients during FEP.

Which mixed depression model? A comparison between DSM-5-defined mixed features and Koukopoulos' criteria.

BACKGROUND: The criteria of the Diagnostic and Statistical Manual of Mental Disorders 5th edition "with mixed features specifier" (DSM-5 MFS) are considered controversial since they include only typical manic symptoms. By contrast, Koukopoulos developed an alternative model of mixed depression (MxD) focusing primarily on the excitatory component. OBJECTIVE: To compare DSM-5 MFS and Koukopoulos' MxD (KMxD) in terms of prevalence, associated clinical variables, and discriminative capacity for bipolar depression in patients with major depressive episode (MDE). METHODS: A total of 300 patients with MDE-155 with major depressive disorder and 145 with bipolar disorder (BD)-were recruited. The discriminative capacity of DSM-5 MFS and KMxD criteria for BD was estimated using the area under the curves of receiver operating characteristic (ROC_AUC). The clinical variables associated with these two diagnostic constructs were assessed by performing a logistic regression. RESULTS: A total of 44 and 165 patients met the DSM-5 MFS and KMxD criteria, respectively. The ROC_AUCs and their confidence intervals for BD according to DSM-5 MFS and KMxD were 77.0% (72.0%-82.1%) and 71.9% (66.2%-77.7%), respectively. The optimal thresholds (combining sensitivity and specificity measures) for BD diagnosis were ≥1 (77%/68%) for DSM-5 MFS and ≥3 symptoms (78%/66%) for KMxD. However, considering the DSM-5 MFS cut-off (≥3 symptoms), the specificity (97%) increased at the expense of sensitivity (26%). CONCLUSIONS: KMxD and DSM-5-MFS showed an overlapping discriminative capacity for bipolar depression. The current diagnostic threshold of DSM-5 MFS did not prove to be very inclusive, if compared with the greater diagnostic sensitivity of KMxD, which also yielded better association with clinical variables related to mixedness.

Assessing response, remission, and treatment resistance in patients with obsessive-compulsive disorder with and without tic disorders: results from a multicenter study.

BACKGROUND: Highlighting the relationship between obsessive-compulsive disorder (OCD) and tic disorder (TD), two highly disabling, comorbid, and difficult-to-treat conditions, Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) acknowledged a new "tic-related" specifier for OCD, ie, obsessive-compulsive tic-related disorder (OCTD). As patients with OCTD may frequently show poor treatment response, the aim of this multicenter study was to investigate rates and clinical correlates of response, remission, and treatment resistance in a large multicenter sample of OCD patients with versus without tics. METHODS: A sample of 398 patients with a DSM-5 diagnosis of OCD with and without comorbid TD was assessed from 10 different psychiatric departments across Italy. For the purpose of the study, treatment response profiles in the whole sample were analyzed comparing the rates of response, remission, and treatment-resistance as well as related clinical features. Multivariate logistic regressions were performed to identify possible factors associated with treatment response. RESULTS: The remission group was associated with later ages of onset of TD and OCD. Moreover, significantly higher rates of psychiatric comorbidities, TD, and lifetime suicidal ideation and attempts emerged in the treatment-resistant group, with larger degrees of perceived worsened quality of life and family involvement. CONCLUSIONS: Although remission was associated with later ages of OCD and TD onset, specific clinical factors, such as early onset and presence of psychiatric comorbidities and concomitant TD, predicted a worse treatment response with a significant impairment in quality of life for both patients and their caregivers, suggesting a worse profile of treatment response for patients with OCTD.

Factors associated with lifetime suicide attempts in bipolar disorder: results from an Italian nationwide study.

The purpose of the present study was to detect demographic and clinical factors associated with lifetime suicide attempts in Bipolar Disorder (BD). A total of 1673 bipolar patients from different psychiatric departments were compared according to the lifetime presence of suicide attempts on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (presence of suicide attempts) at the univariate analyses, preliminary multiple logistic regression analyses were realized. A final multivariable logistic regression was then performed, considering the presence of lifetime suicide attempts as the dependent variable and statistically significant demographic/clinical characteristics as independent variables. The final multivariable logistic regression analysis showed that an earlier age at first contact with psychiatric services (odds ratio [OR] = 0.97, p < 0.01), the presence of psychotic symptoms (OR = 1.56, p < 0.01) or hospitalizations (OR = 1.73, p < 0.01) in the last year, the attribution of symptoms to a psychiatric disorder (no versus yes: OR = 0.71, partly versus yes OR = 0.60, p < 0.01), and the administration of psychoeducation in the last year (OR = 1.49, p < 0.01) were all factors associated with lifetime suicide attempts in patients affected by BD. In addition, female patients resulted to have an increased association with life-long suicidal behavior compared to males (OR: 1.02, p < 0.01). Several clinical factors showed complex associations with lifetime suicide attempts in bipolar patients. These patients, therefore, require strict clinical monitoring for their predisposition to a less symptom stabilization. Future research will have to investigate the best management strategies to improve the prognosis of bipolar subjects presenting suicidal behavior.