A "transatlantic" follow-up study of the impact of the COVID-19 pandemic on patients with obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive symptom fluctuations may be contingent on the number of stressful pandemic-related events and the resilience characterizing different cultures. We investigated the influence of the pandemic on symptom changes in a sample of obsessive-compulsive disorder (OCD) patients from Brazil and Italy, two countries that were highly affected by the outbreak. METHODS: Ninety-one OCD outpatients were evaluated at baseline and about one year later. Thirty of them were assessed in Brazil and 61 in Italy. Socio-demographic variables, symptoms' severity and the number of stressful pandemic-related events were collected. Comparisons between countries' samples were performed, and a linear regression examined whether the country of origin, demographic features and the number of stressful events were able to predict the symptoms' severity at the follow-up. RESULTS: Brazilian patients experienced more stressful pandemic-related events than Italian patients (p = 0.018). However, along with higher age (p < 0.01) and increased severity of symptoms at baseline (p < 0.01), lower number of events predicted increased symptoms' severity after one year (p < 0.01). Country of origin was not a significant predictor of severity. LIMITATIONS: Small number of subjects; lack of information regarding duration of illness; and potential sample differences between countries. CONCLUSIONS: During the pandemic, the occurrence of more stressful pandemic-related events was associated with decreased severity of patients' OCD symptoms. Nevertheless, older patients and those with more severe symptoms seemed prone to exhibit increased OCD severity at follow-up.

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.

Googling for Suicide-Content and Quality Analysis of Suicide-Related Websites: Thematic Analysis.

BACKGROUND: Suicide represents a public health concern, imposing a dramatic burden. Prosuicide websites are "virtual pathways" facilitating a rise in suicidal behaviors, especially among socially isolated, susceptible individuals. OBJECTIVE: The aim of this study is to characterize suicide-related webpages in the Italian language. METHODS: The first 5 most commonly used search engines in Italy (ie, Bing, Virgilio, Yahoo, Google, and Libero) were mined using the term "suicidio" (Italian for suicide). For each search, the first 100 webpages were considered. Websites resulting from each search were collected and duplicates deleted so that unique webpages could be analyzed and rated with the HONcode instrument. RESULTS: A total of 65 webpages were included: 12.5% (8/64) were antisuicide and 6.3% (4/64) explicitly prosuicide. The majority of the included websites had a mixed or neutral attitude toward suicide (52/64, 81.2%) and had informative content and purpose (39/64, 60.9%). Most webpages targeted adolescents as an age group (38/64, 59.4%), contained a reference to other psychiatric disorders or comorbidities (42/64, 65.6%), included medical/professional supervision or guidance (45/64, 70.3%), lacked figures or pictures related to suicide (41/64, 64.1%), and did not contain any access restraint (62/64, 96.9%). The major shortcoming to this study is the small sample size of webpages analyzed and the search limited to the keyword "suicide." CONCLUSIONS: Specialized mental health professionals should try to improve their presence online by providing high-quality material.

Delirium in COVID-19 patients: a multicentric observational study in Italy.

INTRODUCTION: Although recent data show that SARS-CoV-2 infection seems to affect the central nervous system (CNS), little is known about the neuropsychiatric effects resulting from this condition. In addition to the well-known neurotrophism of coronaviruses, recent evidence shows also that the "cytokine storm" induced by the infection is at the basis of the neuroinflammation of the CNS. Furthermore, prolonged hospitalization, polypharmacotherapy, and isolation could be at the basis of the onset of delirium in hospitalized COVID patients. This multicentric observational study explores the incidence of the onset of delirium in an Italian cohort of SARS-CoV-2 positive inpatients. METHODS: Data were collected in the COVIDhospitals of Brescia, Bergamo, Chieti, and Genova. Different socio-demographic, medical, neurological, and pharmacological parameters were collected. As a rapid screening for delirium, the 4AT scale was used. Eighty COVID-19 inpatients (mean age 74.7 ± 14.5 years) met the inclusion criteria (confirmed positivity to the SARS-CoV-2 virus; the presence of delirium and/or psychomotor agitation and/or new onset of other neuropsychiatric symptoms during hospitalization). RESULTS: The majority of these patients (68.8%) had "hyperactive delirium" subtype. Polypharmacotherapy, current treatment with corticosteroids, and higher age were associated with delirium severity. CONCLUSION: These data provide an insight into the onset of delirium among COVID-19 patients underlining the need for monitoring, especially in elderly patients, the neuropsychiatric symptoms, and the therapy in order to have shorter hospitalization times and better outcomes.

Cannabinoid use and self-injurious behaviours: A systematic review and meta-analysis.

BACKGROUND: The increasing availability of high-potency cannabis-derived compounds and the use of synthetic cannabinoids may be responsible for severe side effects like cognitive impairment, psychosis or self-injurious behaviours (SIB). In particular, SIB like non-suicidal self-injury (NSSI) and deliberate self-harm (DSH) raise growing concern as a possible consequence of cannabis use. However, the research to date has not addressed the relationship between cannabinoid use and SIB systematically. METHODS: We conducted a systematic review on PubMed up to March 2020, using search terms related to cannabinoids and SIB. RESULTS: The search yielded a total of 440 abstracts. Of those, 37 studies published between 1995 and 2020 were eligible for inclusion. Cannabinoid use was significantly associated with SIB at the cross-sectional (OR=1.569, 95%CI [1.167-2.108]) and longitudinal (OR=2.569, 95%CI [2.207-3.256]) level. Chronic use, presence of mental disorders, depressive symptoms, emotional dysregulation and impulsive traits might further increase the likelihood of self-harm in cannabis users. Synthetic cannabinoids may trigger highly destructive SIB mainly through the psychotomimetic properties of these compounds. CONCLUSION: Cannabinoid use was associated with an increased prevalence of self-injury and may act as a causative factor with a duration-dependent manner. Emotional regulation and behavioural impulsivity functions might crucially moderate this association. Future studies should further investigate the mechanisms underlying this association, while exploring potential therapeutic applications of substances modulating the endocannabinoid system.

Sexual response in obsessive-compulsive disorder: the role of obsessive beliefs.

BACKGROUND: Sexual response in obsessive-compulsive disorder (OCD) research and practice is overlooked. According to the Dual Control Model, satisfactory sexual response is based upon a balance of sexual excitation and inhibition. The assessment of sexual response in OCD may have clinical implications, such as the integration of sex therapy in psychotherapeutic intervention. The present study was aimed at comparing sexual excitation and inhibition levels between OCD patients and matched control subjects, and investigating whether obsessive beliefs might predict sexual excitation/inhibition. METHODS: Seventy-two OCD patients (mean age ± standard deviation [SD]: 34.50 ± 10.39 years) and 72 matched control subjects (mean age ± SD: 34.25 ± 10.18) were included (62.50% men and 37.50% women in both groups). The Obsessive Compulsive Inventory-Revised (OCI-R), the Obsessive Beliefs Questionnaire-46 (OBQ-46), and the Sexual Inhibition/Sexual Excitation Scales (SIS/SES) were administered. RESULTS: Patients with OCD showed significantly higher levels of sexual excitation, inhibition due to threat of performance failure, and inhibition due to threat of performance consequences than the controls. In addition, the patients with more severe symptoms showed lower excitation than those with less severe symptoms, and those with higher perfectionism had stronger inhibition due to threat of performance failure than those with lower perfectionism. CONCLUSIONS: This is the first study exploring sexual response in OCD according to the Dual Control Model. Sexual response is an impaired quality of life outcome in OCD that should be assessed in routine clinical practice. These findings support the importance of addressing specific obsessive beliefs to improve sexuality in OCD patients.

Sexual Arousal in Obsessive-Compulsive Disorder With and Without Contamination/Washing Symptoms: A Moderating Role of Disgust Sensitivity.

Different findings would indicate that obsessive-compulsive disorder (OCD), a common psychiatric condition, might significantly impair intimate relationships and sexual well-being. The aim of the present study was to ascertain whether OCD outpatients with contamination/washing symptoms experience a lower sexual arousal than those experiencing other symptoms. In addition, we explored whether a higher disgust propensity/sensitivity might moderate the relation between contamination/washing symptoms and impaired sexual arousal. A total of 72 outpatients (27 with contamination/washing symptoms and 45 with other obsessive-compulsive symptoms) were selected for this study and assessed by a battery of specific rating scales. The results highlighted how OCD patients with contamination/washing symptoms and higher disgust sensitivity showed an increased propensity to inhibition due to threat of sexual performance failure and consequences. It may be speculated that the disgust sensitivity may be a mechanism involved in the impairment of this well-being domain. In conclusion, these findings suggest that the sexual wellbeing should be evaluated during routine clinical evaluation of OCD patients.

Sexual dysfunction and satisfaction in obsessive compulsive disorder: protocol for a systematic review and meta-analysis.

BACKGROUND: Obsessive compulsive disorder (OCD) is a chronic mental health condition recognized as one of the most serious causes of disability and impaired quality of life. In the literature, there is no review about sexual dysfunction and satisfaction in OCD. The current paper presents the protocol for a systematic review and meta-analysis aimed to summarize data (1) comparing the presence of sexual dysfunction between groups with OCD and non-clinical groups, (2) investigating prevalence of each one of the sexual dysfunctions in patients with OCD, (3) comparing risk for sexual dysfunction in OCD groups with the prevalence in control groups, (4) comparing sexual satisfaction between OCD groups and non-clinical groups, and (5) investigating moderators of sexual dysfunction in OCD groups as compared with control groups. Gender, age, marital status, OCD symptom severity and subtypes, comorbid depressive disorders, comorbid anxiety disorders, concurrent psychiatric medications, comorbid general medical disease, and study quality will be investigated as moderators. METHODS: The protocol is reported according to PRISMA-P guidelines. The search will be conducted by independent reviewers during the second week of December 2019 by using electronic databases (Scopus, PubMed, EMBASE, PsycINFO, CINAHL, and the Cochrane Library), by contacting the authors of the included studies to identify further data, by examining the references of the included studies, and by handsearching conference proceedings and theses/doctoral dissertations. The study quality will be independently evaluated using the Newcastle-Ottawa Quality Assessment Scale. Random-effect meta-analyses will be computed. If there is insufficient data for a specific outcome, only a systematic review will be performed. DISCUSSION: This review may support clinical practice highlighting the importance of the assessment of sexuality in patients with OCD and suggesting the use of therapeutic strategies dedicated to sexuality in this clinical population with the aim of improving patients' quality of life. Potential limitations will regard the heterogeneity of the studies in terms of the instruments used to assess sexual dysfunction/satisfaction and of the definitions used to conceptualize sexual dysfunction. SYSTEMATIC REVIEW REGISTRATION: Prospero CRD42019132264.

Reasons for initiating long-acting antipsychotics in psychiatric practice: findings from the STAR Network Depot Study.

BACKGROUND: Long acting injectable (LAI) antipsychotics have been claimed to ensure treatment adherence and possibly reduce the daily burden of oral formulations. So far, only surveys investigating the theoretical prescribing attitudes of clinicians have been employed. On this basis, we aimed to investigate reasons for prescribing LAIs in a real-world, unselected sample of patients. METHODS: The STAR Network Depot Study is an observational, multicentre study consecutively enrolling adults initiating a LAI over a 12-months period. Clinical severity was assessed with the Brief Psychiatric Rating Scale, and patient's attitude toward medications with the Drug Attitude Inventory 10 items. Psychiatrists recorded reasons for LAI prescribing for each study participant. Responses were grouped into six non-mutually exclusive categories: aggressiveness, patient engagement, ease of drug taking, side-effects, stigma, adherence. RESULTS: Of the 451 patients included, two-thirds suffered from chronic psychoses. Improving patient engagement with the outpatient psychiatric service was the most common reason for prescribing LAIs (almost 80% of participants), followed by increasing treatment adherence (57%), decreasing aggressiveness (54%), and improving ease of drug taking (52%). After adjusting for confounders, logistic regression analyses showed that reasons for LAI use were associated with LAI choice (e.g. first-generation LAIs for reducing aggressiveness). CONCLUSION: Despite the wide availability of novel LAI formulation and the emphasis on their wider use, our data suggest that the main reasons for LAI use have remained substantially unchanged over the years, focusing mostly on improving patient's engagement. Further, clinicians follow implicit prescribing patterns when choosing LAIs, and this may generate hypotheses for future experimental studies.

A Pilot Study of Gender Differences in Sexual Arousal of Patients With OCD: The Moderator Roles of Attachment and Contamination Symptoms.

Sexual arousal is often impaired in patients with obsessive-compulsive disorder (OCD). However, little is known about the factors related to this impairment: no study focused on the role of gender-based effects of attachment styles and contamination symptoms. The Dual Control Model assumes three processes driving sexual arousal: sexual excitation (SE), sexual inhibition (SI) due to threat of performance failure, and SI due to threat of performance consequences (e.g., getting contaminated with sexually transmitted diseases). In a group of OCD patients, we hypothesized that (a) women report lower SE and higher SI than men; (b) patients with insecure (both anxious and avoidant) attachment styles show lower SE and higher SI; (c) attachment styles moderate the relation between gender and sexual arousal (respectively, for women, higher attachment anxiety, and for men higher attachment avoidance were related to impaired sexual arousal (higher SE and SI) controlling for OCD severity); and (d) contamination symptoms moderate the relation between gender and sexual impairment (women with contamination symptoms show impaired sexual arousal). Seventy-two OCD patients (37.50% women) completed the Obsessive-Compulsive Inventory-Revised, Attachment Styles Questionnaire and Sexual Inhibition/Sexual Excitation Scales. In contrast with our hypotheses, women reported higher SE and lower SI due to threat of performance consequences than men. Patients with higher attachment avoidance (discomfort with intimacy) but also confidence in self and others had higher SE. Women with attachment avoidance (i.e., discomfort with intimacy) had lower SE, while women with attachment anxiety (i.e., preoccupations with relationships) had higher SI due to negative performance consequences. Women with contamination symptoms had higher SI due to performance failure but lower SI due to performance consequences. The present preliminary findings suggest that sexual arousal impairment should be evaluated during the assessment of OCD patients, and gender-based effects of attachment styles and contamination symptoms should be considered during personalized treatment planning.

The role of disgust propensity and sensitivity on sexual excitations and inhibition in obsessive-compulsive disorder.

Sexuality is understudied in Obsessive-Compulsive Disorder (OCD). According to the Dual Control Model, low sexual excitation (SE) and high sexual inhibition (SI) are indicative of a higher probability of experiencing a sexual dysfunction. The present study investigated SE and SI in OCD patients compared with controls. It was hypothesized that OCD patients report lower SE and higher SI than controls. Given their potential role as inhibitors of sexual response, it was hypothesized that in the OCD group higher disgust propensity/sensitivity, contamination/washing symptoms, unacceptable thoughts, and obsessive beliefs predicted lower SE, higher SI due to Threat of Performance Failure, and higher SI due to Threat of Performance Consequences. Seventy-two OCD patients and 72 controls matched on gender/age completed the Disgust Propensity and Sensitivity Scale-Revised, Obsessive Beliefs Questionnaire-46, Obsessive Compulsive Inventory- Revised, and Sexual Inhibition/Sexual Excitation Scales. OCD patients had higher SE, SI due to Threat of Performance Failure, and SI due to Threat of Performance Consequences than controls. In the OCD group, higher disgust sensitivity, SI due to Threat of Performance Consequences, and perfectionism predicted higher SI due to Threat of Performance Failure. Higher SI due to Threat of Performance Failure and contamination/washing symptoms predicted higher SI due to Threat of Performance Consequences. These findings highlight the presence of sexual difficulties in OCD patients, particularly a higher SE and SI. The latter is especially relevant in those patients with higher disgust sensitivity, contamination/washing symptoms and perfectionism. Psychotherapists should assess and target sexuality during clinicalpractice with OCD patients.

Tratamiento con aripiprazol en la práctica clínica: consenso de un panel de expertos / Treatment with aripiprazole in clinical practice: Expert consensus panel

Objetivo: Revisión de la evidencia científica sobre el manejo clínico del aripiprazol. Metodología: Un panel de expertos formado por 7 miembros discutió una serie de casos clínicos. Cuando se llegó a un consenso, sacaron sus conclusiones. Además, se revisaron e incluyeron los datos y la evidencia clínica de los ensayos clínicos de aripiprazol más relevantes de los últimos 10años. Resultados: El aripiprazol por vía oral es eficaz para el tratamiento de los pacientes con esquizofrenia y trastorno bipolar, tanto en la fase aguda como en la fase de mantenimiento. También demostró ser eficaz para evitar las recaídas. La administración intramuscular es útil en el manejo de la agitación en esos pacientes. La presentación inyectable de liberación prolongada ha tenido resultados positivos en el retraso de la recaída en pacientes esquizofrénicos y bipolares, y mejora el cumplimiento del tratamiento. El aripiprazol es un fármaco bien tolerado y los efectos adversos, como somnolencia, aumento de peso, trastornos metabólicos o eventos cardiovasculares, son menos frecuentes que para otros fármacos antipsicóticos. El aripiprazol ha sido bien tolerado cuando se usa en combinación con otros antipsicóticos, debido a sus interacciones limitadas. Conclusiones: Los datos de los estudios revisados y el consenso del panel de expertos mostraron que el aripiprazol es un tratamiento efectivo y bien tolerado para los pacientes con esquizofrenia, trastorno esquizoafectivo, trastorno bipolar moderado a grave y episodios maníacos. Su uso también conduce a una mejor adherencia. La menor frecuencia de sedación y el hecho de que no afecte a la función cognitiva del paciente mejoran la adherencia y colocan al aripiprazol en una buena posición como opción terapéutica

Objective: To review the scientific evidence on the clinical management of aripiprazole. Methodology: A seven-member expert panel discussed a series of clinical cases. When a consensus was reached, they drew their conclusion. They also reviewed, and included data and clinical evidence from the most relevant aripiprazole clinical trials from the last 10years. Results: Oral aripiprazole is effective for the treatment of patients with schizophrenia and bipolar disorder, both in the acute and maintenance phase. It was also shown to be effective to prevent relapses. Intramuscular administration is useful in the management of agitation in these patients. The presentation of prolonged action has had positive results in the delay of a relapse in schizophrenic and bipolar patients, and improves treatment compliance. Aripiprazole is a well-tolerated drug and the secondary effects, such as drowsiness, increase in weight, metabolic disorders, or cardiovascular events are less common than in other antipsychotic drugs. Aripiprazole has been well-tolerated when it was used in combination with other antipsychotic drugs, due to their limited interaction. Conclusions: The data from the reviews studied and the consensus of the Expert Panel showed that Aripiprazole is an effective and well-tolerated treatment for patients with schizophrenia, schizo-affective disorders, moderate to severe bipolar disorder, and manic episodes. Its use leads to improved adherence. The lower sedation frequency and the fact that it does affect the cognitive function of the patient improves adherence and places aripiprazole in a good position as a therapeutic option

The HPA axis in bipolar disorder: Systematic review and meta-analysis.

OBJECTIVES: To provide a quantitative and qualitative synthesis of the available evidence on the role of Hypothalamic-Pituitary-Adrenal (HPA) axis in the pathophysiology of Bipolar Disorder (BD). METHODS: Meta-analysis and meta-regression of case-control studies examining the levels of cortisol, ACTH, CRH levels. Systematic review of stress reactivity, genetic, molecular and neuroimaging studies related to HPA axis activity in BD. RESULTS: Forty-one studies were included in the meta-analyses. BD was associated with significantly increased levels of cortisol (basal and post-dexamethasone) and ACTH, but not of CRH. In the meta-regression, case-control differences in cortisol levels were positively associated with the manic phase (p=0.005) and participants' age (p=0.08), and negatively with antipsychotics use (p=0.001). Reviewed studies suggest that BD is associated with abnormalities of stress-related molecular pathways in several brain areas. Variants of HPA axis-related genes seem not associated with a direct risk of developing BD, but with different clinical presentations. Also, studies on unaffected relatives suggest that HPA axis dysregulation is not an endophenotype of BD, but seems related to environmental risk factors, such as childhood trauma. Progressive HPA axis dysfunction is a putative mechanism that might underlie the clinical and cognitive deterioration of patients with BD. CONCLUSIONS: BD is associated with dysfunction of HPA axis activity, with important pathophysiological implications. Targeting HPA axis dysfunctions might be a novel strategy to improve the outcomes of BD.

Absence of bias in clinician ratings of everyday functioning among African American, Hispanic and Caucasian patients with schizophrenia.

A substantial research literature implicates potential racial/ethnic bias in the diagnosis of schizophrenia and in clinical ratings of psychosis. There is no similar information regarding bias effects on ratings of everyday functioning. Our aims were to determine if Caucasian raters vary in their ratings of the everyday functioning of schizophrenia patients of different ethnicities, to find out which factors determine accurate self-report of everyday functioning in different ethnic groups, and to know if depression has similar effects on the way people of different ethnicities self-report their current functionality. We analyzed data on 295 patients with schizophrenia who provided their self-report of their everyday functioning and also had a Caucasian clinician rating their functionality. Three racial/ethnic groups (African American (AA), Hispanic and Caucasian) were studied and analyzed on the basis of neurocognition, functional capacity, depression and real-world functional outcomes. No differences based on racial/ethnic status in clinician assessments of patients' functionality were found. Differences between racial groups were found in personal and maternal levels of education. Severity of depression was significantly correlated with accuracy of self-assessment of functioning in Caucasians, but not in AAs. Higher scores on neurocognition and functional capacity scales correlated with reduced overestimation of functioning in AAs, but not in Hispanics. This data might indicate that measurement of everyday functionality is less subject to rater bias than measurement of symptoms of schizophrenia.

Social competence versus negative symptoms as predictors of real world social functioning in schizophrenia.

Deficits in real world social functioning are common in people with schizophrenia and the treatment of social skills deficits has been a long-time treatment strategy. However, negative (i.e., deficit) symptoms also appear to contribute to real-world social dysfunction. In this study, we combined data from three separate studies of people with schizophrenia (total n=561) who were assessed with identical methods. We examined the prediction of real-world social functioning, rated by high contact clinicians, and compared the influence of negative symptoms and social skills measured with performance-based methods on these outcomes. Negative symptom severity accounted for 20% of the variance in real-world social functioning, with social skills adding an incremental 2%. This 2% variance contribution was the same when social skills were forced into a regression model prior to negative symptom severity. When we examined individual negative symptoms, prediction of real-world social functioning increased to 28%, with active and passive social avoidance entering the equation. Adding depression into the predictor model improved the prediction of real-world social functioning significantly, but minimally (4% variance). Social skills contribute to real-world social outcomes, but treating negative symptoms appears to be a possible path for improving real-world social functioning in this population.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial.

BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size. METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome. RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected. CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

The Course and Correlates of Everyday Functioning in Schizophrenia.

Previously institutionalized older patients with schizophrenia show changes in cognitive and functional capacity over time. This study examined changes in real-world functioning in a sample of people with schizophrenia who varied in their history of long-term institutionalization and related changes in real world functioning to changes in cognition and functional capacity over the follow-up period. Older patients with schizophrenia (n=111) were examined with assessments of cognitive functioning, functional capacity, clinical symptoms, and everyday functioning. They were then followed up to 45 months and examined up to two times. Mixed-model regression was used to examine changes in real-world functioning in social, everyday living, and vocational domains over the follow-up period and identify potential predictors of change. Everyday functioning worsened over time in all three domains. Although length of longest hospitalization predicted worsening, this influence was eliminated when the course of functional capacity was used to predict the course of everyday functioning. For both vocational and everyday living domains, as well as the composite score on functional status, worsening in performance based measures of everyday functioning and social competence predicted worsening in real world functioning. Changes in negative symptoms further predicted worsening in the everyday living domain. Worsening in everyday functioning is found in people with schizophrenia and those with a history of greater chronicity and severity of illness seem more affected. These influences seem to be expressed through worsening in the ability to perform everyday functional skills. Potential causes of these changes and implications for reducing these impairments are discussed.

Duloxetine-bupropion combination for treatment-resistant atypical depression: a double-blind, randomized, placebo-controlled trial.

The efficacy, safety, and tolerability of combined bupropion versus placebo using duloxetine as active reference drug, in patients with a DSM-IV diagnosis of major depression with atypical features and a history of treatment resistance, were evaluated in this preliminary six-week study. Patients (n=46) had a baseline Hamilton Depression Scale (HAM-D) ≥14 and were randomly assigned to 150/300 mg/day bupropion vs. placebo, which was added to 60 to 120 mg/day duloxetine depending on baseline depression severity. Atypical features of depression were assessed using the additional eight-item module of the Structured Interview Guide for the HAM-D with the Atypical Depression Supplement. By week 6, only five (21.7%) patients receiving duloxetine+placebo vs. six (26.1%) patients on the bupropion combination achieved response. No significant difference in final HAM-D scores between the two groups was observed between those patients achieving response. The presence of a higher number of atypical features significantly predicted non-response, with the relevant binary logistic regression model correctly classifying 17 out 22 (77.3%) of non-responders [Exp(B)=0.294; p=0.016] vs. 17 out 23 (73.9%) [Exp(B)=0.353; p=0.028] non-responder cases in the "+placebo" and "+bupropion" groups, respectively. In those patients receiving bupropion, treatment-emergent adverse events leading to withdrawal were more common among those receiving lower doses of the combination drug, and no life-threating dangers were noted. Additional studies, including an adequate course of duloxetine trial, are nonetheless aimed to allow a firm conclusion about the usefulness of the combination of duloxetine and bupropion for treatment-resistant cases of major depression with atypical features.