Alessandro Cuomo

Prevalence, chronicity, burden and borders of bipolar disorder

Bipolar disorder (BD) has traditionally been thought of as an episodic condition, characterized by periods of hypomania/mania and depression. However, evidence is accumulating to suggest that this condition is associated with significant chronicity. For a large proportion of patients with BD, residual, sub-syndromal symptoms persist between major syndromal episodes, and studies have shown that many patients with bipolar disorder are symptomatic for approximately 50% of the time over follow-up periods of greater than 10 years. Moreover, while the prevalence of BD has been estimated to be around 1-2%, there is growing evidence that this may be a substantial underestimation. There are a number of reasons for this potential underestimation, including difficulties in diagnosis. Adding to the burden of BD is the issue of comorbidity, with an increased prevalence of many chronic conditions in those with a primary diagnosis of BD. Conversely, for many patients with chronic conditions, both medical and psychiatric, BD frequently exists as a comorbid secondary diagnosis. This issue of comorbidity complicates estimates of use of pharmaceutical agents for BD, such as mood stabilizers, which are known to be used off-label in conditions such as borderline personality or substance use disorder. We speculate that such off-label prescribing may not be truly off-label but may be instead fully justified by an overlooked secondary diagnosis of BD. Finally, we discuss the association of bipolar disorder with a significant economic burden, to the individual and to society, both due to the direct costs of medical expenditure and indirect costs such as loss of productivity and increased mortality.

Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice

Introduction: Asenapine is a sublingually administered second-generation antipsychotic with proven efficacy for the treatment of moderate to severe manic episodes associated with bipolar I disorder in adults. Its relatively favorable weight and metabolic profile, as well as the lack of appreciable activity at muscarinic cholinergic receptors and the sublingual administration are of clinical interest. Areas covered: This paper comprises a review and commentary regarding the use of sublingual asenapine in the treatment of acute manic and mixed episodes of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration with other medications are provided. Expert opinion: Asenapine displays quick and reliable effects on manic symptoms, very low risk of depressive switches, efficacy on depressive symptoms during manic and mixed episodes, usually good tolerability and continued longer-term efficacy on residual and subthreshold symptoms. The fast-dissolving sublingual route of administration may favor those who have difficulties in swallowing medications. Also, the sublingual administration reduces the risk of overdose when more than the prescribed tablets are swallowed. The relatively low metabolic risk and the lack of anticholinergic side effects contribute to making this medication a useful tool for the treatment of patients with bipolar disorder.

Interplay among psychopathologic variables, personal resources, context-related factors, and real-life functioning in individuals with schizophrenia a network analysis

Importance Enhanced understanding of factors associated with symptomatic and functional recovery is instrumental to designing personalized treatment plans for people with schizophrenia. To date, this is the first study using network analysis to investigate the associations among cognitive, psychopathologic, and psychosocial variables in a large sample of community-dwelling individuals with schizophrenia. Objective To assess the interplay among psychopathologic variables, cognitive dysfunctions, functional capacity, personal resources, perceived stigma, and real-life functioning in individuals with schizophrenia, using a data-driven approach. Design, Setting, and Participants This multicenter, cross-sectional study involved 26 university psychiatric clinics and/or mental health departments. A total of 921 community-dwelling individuals with a DSM-IV diagnosis of schizophrenia who were stabilized on antipsychotic treatment were recruited from those consecutively presenting to the outpatient units of the sites between March 1, 2012, and September 30, 2013. Statistical analysis was conducted between July 1 and September 30, 2017. Main Outcomes and Measures Measures covered psychopathologic variables, neurocognition, social cognition, functional capacity, real-life functioning, resilience, perceived stigma, incentives, and service engagement. Results Of 740 patients (221 women and 519 men; mean [SD] age, 40.0 [10.9] years) with complete data on the 27 study measures, 163 (22.0%) were remitted (with a score of mild or better on 8 core symptoms). The network analysis showed that functional capacity and everyday life skills were the most central and highly interconnected nodes in the network. Psychopathologic variables split in 2 domains, with positive symptoms being one of the most peripheral and least connected nodes. Functional capacity bridged cognition with everyday life skills; the everyday life skills node was connected to disorganization and expressive deficits. Interpersonal relationships and work skills were connected to avolition; the interpersonal relationships node was also linked to social competence, and the work skills node was linked to social incentives and engagement with mental health services. A case-dropping bootstrap procedure showed centrality indices correlations of 0.75 or greater between the original and randomly defined samples up to 481 of 740 case-dropping (65.0%). No difference in the network structure was found between men and women. Conclusions and Relevance The high centrality of functional capacity and everyday life skills in the network suggests that improving the ability to perform tasks relevant to everyday life is critical for any therapeutic intervention in schizophrenia. The pattern of network node connections supports the implementation of personalized interventions.

Does higher severity really correlate with a worse quality of life in obsessive-compulsive disorder? A meta-regression

Background Obsessive–compulsive disorder (OCD) is one of the leading causes of disability and reduced quality of life (QOL), with impairment in a number of domains. However, there is a paucity of literature on the association between severity of OCD symptoms and QOL, and the data that do exist are inconsistent. In addition, the role of severity in QOL has not been summarized as yet from a cross-generational perspective (ie, across childhood/adolescence and adulthood). Through meta-regression techniques, the current study summarized evidence about the moderator role of severity of OCD symptoms on differences in global QOL between individuals with OCD and controls. Methods Online databases were searched, and cross-sectional case–control studies comparing participants of all ages with OCD with controls on self-report QOL measures were included. Random-effect meta-regression techniques were used to comment on the role of illness severity in global QOL in individuals with OCD. Results Thirteen studies were included. A positive significant association emerged between OCD severity and effect sizes on global QOL: in samples with higher severity, there were narrower differences in QOL between patients with OCD and controls than in samples with lower severity. Such positive association was confirmed by a sensitivity analysis conducted on studies including only adults, where the difference in QOL ratings between patients and controls was significantly narrower when OCD severity was higher. Conversely, a negative association between severity and QOL was found in those studies including only children/adolescents, where the difference in QOL was significantly larger between patients and controls when OCD severity was higher. Conclusion QOL remains an important issue to address in the management of OCD in all age groups, irrespective of illness severity. Even in those with lower severity ratings, QOL may be considered as an important marker of treatment response.

Practical guidance for prescribing trazodone extended-release in major depression

Abstract Introduction: Treatment of major depressive disorder aims for symptom remission and recovery of function, and involves a multifaceted approach including drug therapy, evidence-based psychotherapy, and electroconvulsive therapy, according to disease severity. Antidepressant monotherapy is generally the first-line approach for moderate to severe major depressive disorder (with or without psychotherapy). In some severe cases, patients may require the addition of antipsychotic therapy, electroconvulsive therapy, or antidepressant combination therapy. Areas covered: This article examines the use of trazodone in major depressive disorder, with a focus on practical guidance regarding the use of trazodone extended-release (Contramid®). Expert opinion: The extended-release once-a-day formulation of trazodone may provide a combination of efficacy and improved tolerability over other antidepressants and over the conventional immediate-release formulation.

Disorganization and real-world functioning in schizophrenia: Results from the multicenter study of the Italian Network for Research on Psychoses

BACKGROUND A general consensus has not yet been reached regarding the role of disorganization symptoms in real-world functioning in schizophrenia. METHODS We used structural equations modeling (SEM) to analyze the direct and indirect associations between disorganization and real-world functioning assessed through the Specific Levels of Functioning Scale (SLOF) in 880 subjects with schizophrenia. RESULTS We found that: 1) conceptual disorganization was directly and strongly connected with SLOF daily activities; difficulty in abstract thinking was associated with moderate strength to all SLOF domains, and poor attention was connected with SLOF work skills; 2) grandiosity was only related with poor work skills, and delusions were associated with poor functioning in all SLOF domains; interpersonal relationships were weakly indirectly influenced by hallucinatory behavior, delusions and unusual thought contents through the mediation of social cognition (SC); 3) among the negative symptoms, avolition had only direct links with SLOF work skills and SLOF activities; anhedonia had direct links with SLOF work skills and SLOF interpersonal and indirect link with SLOF work skills through functional capacity (FC); asociality with SLOF interpersonal; blunted affect had direct links with SLOF activities and indirect links with SLOF interpersonal relationships mediated by SC. Lastly, alogia had only indirect links mediated by SC, FC, and neurocognition (NC). CONCLUSIONS Overall conceptual disorganization is the symptom that contributed more (both directly and indirectly) to the activities of community living in real-world. Thus, it should be considered as a treatment target in intervention programs for patients with schizophrenia.

Medication-Associated Sexual Dysfunction in Patients with Mental Illness

Sexual dysfunction (SD) is a frequent and distressing side effect of many psychotropic medications, including serotonergic antidepressants, antipsychotic medications, and mood stabilizers. Psychotropic medications may negatively influence any of the areas of sexual functioning, including libido, arousal, and orgasm. Sexual dysfunction is a threat to patients’ quality of life and frequently affects partners’ quality of life as well. Yet, SD is often underestimated both in clinical trials and in clinical practice. In fact, many patients feel embarrassed to spontaneously discuss side effects that involve sexual functions, and many study designs and clinicians rely only on spontaneous reports. This chapter provides an overview of medication-induced SD and examines the prevalence, clinical characteristics, causes, and treatment options for this burdensome condition.

Aripiprazole use during pregnancy, peripartum and lactation. A systematic literature search and review to inform clinical practice

BACKGROUND Aripiprazole is used relatively frequently in women with bipolar disorder or schizophrenia in childbearing years, owing to its efficacy and relatively favorable side effect profile. As is the case for other psychotropic medications, for ethical reasons, no prospective randomized placebo controlled trial to assess aripiprazole safety during pregnancy has ever been conducted. However, animal data are available and the amount of exposure and outcome data for human fetuses and infants has recently increased, providing published prospective safety data in relatively large numbers of pregnant women treated with aripiprazole. The aim of this study was to perform a systematic literature search and review to critically evaluate the available data on the use of aripiprazole during pregnancy, peripartum and lactation. METHODS PubMed, PsychInfo, and Cochrane Library were searched using the following search builder: (pregnancy OR pregnant OR gestation OR malformations OR perinatal OR reproduction OR organogenesis OR delivery OR breast-feeding OR lactation or peripartum or obstetric) AND aripiprazole. Reports that met the following pre-defined criteria were included in the present review: (1) published in English language in a peer-reviewed journal; (2) clearly defined use of aripiprazole during pregnancy and/or lactation and/or postpartum; (3) case report, case series, prospective, retrospective or cross-sectional studies. United States and European Medicine Agency prescribing information for aripiprazole were consulted as well and all the references of selected papers were cross checked for information pertaining to the use of aripiprazole during pregnancy, peripartum and lactation. RESULTS A total of 549 items published in a period ranging from 1995 to 2017, were retrieved from the search databases and reference cross check. One-hundred-fifty-three duplicate items were removed, 176 titles were deemed as not pertinent, 220 abstracts and 122 full-text articles were assessed for eligibility and 93 titles were included for qualitative synthesis. United States and European Medicine Agency prescribing information for aripiprazole were consulted and the selected manuscript references were cross checked. No randomized placebo controlled trial was found but relatively large prospective studies, large database studies, and several case reports and case studies were identified and summarized. CONCLUSIONS As is the case for other antipsychotics, definitive evidence on aripiprazole reproductive safety is lacking, but newer safety data are relatively reassuring. In many cases, the potential benefits of aripiprazole for patients with bipolar disorder or schizophrenia outweigh the potential risks.

The Microbiome: A New Target for Research and Treatment of Schizophrenia and its Resistant Presentations? A Systematic Literature Search and Review

Background: The gastrointestinal system hosts roughly 1,800 distinct phyla and about 40,000 bacterial classes, which are known as microbiota, and which are able to influence the brain. For instance, microbiota can also influence the immune response through the activation of the immune system or through the release of mediators that are able to cross the brain blood barrier or that can interact with other substances that have free access to the brain, such as tryptophan and kynurenic acid, which is a metabolite of tryptophan and which has been involved in the pathogenesis of schizophrenia. Objectives: This paper reviews the possible relationships between microbiome, schizophrenia and treatment resistance. Given the possibility of a role of immune activation and alterations, we also describe the relationship between schizophrenia and immune inflammatory response. Finally, we report on the studies about the use of probiotic and prebiotics in schizophrenia. Methods: Cochrane library and PubMed were searched from the year 2000 to 2018 for publications about microbiome, immune-mediated pathology, schizophrenia and neurodevelopmental disorders. The following search string was used: (microbiome or immune mediated) AND (schizophrenia OR neurodevelopmental disorder). Associated publications were hand-searched from the list of references of the identified papers. A narrative review was also conducted about the use of probiotics and prebiotics in schizophrenia. Results: There exists a close relationship between the central nervous system and the gastrointestinal tract, which makes it likely that there is a relationship between schizophrenia, including its resistant forms, and microbiota. This paper provides a summary of the most important studies that we identified on the topic. Conclusions: Schizophrenia in particular, remain a challenge for researchers and practitioners and the possibility of a role of the microbiome and of immune-mediated pathology should be better explored, not only in animal models but also in clinical trials of agents that are able to alter gut microbiota and possibly influence the mechanisms of gastrointestinal inflammation. Microbiome targeted treatments have not been well-studied yet in patients with mental illness in general, and with schizophrenia in particular. Nonetheless, the field is well worth of being appropriately investigated.

Using sertraline in postpartum and breastfeeding: balancing risks and benefits

ABSTRACT Introduction: The World Health Organization recommends newborns to be breastfed but this may be challenging if the mother needs to be treated for depression, since strong evidence to inform treatment choice is missing. Areas covered: We provide a critical review of the literature to guide clinicians who are considering sertraline for the management of depression during postpartum. Expert opinion: Sertraline is one of the safest antidepressants during breastfeeding. In most cases, women already taking sertraline should be advised to breastfeed and continue the medication. We recommend to begin with low doses and to slowly increase the dose up, with careful monitoring of the newborn for adverse effects (irritability, poor feeding, or uneasy sleep, especially if the child was born premature or had low weight at birth). The target dose should be the lowest effective. When feasible, child exposure to the medication may be reduced by avoiding breastfeeding at the time when the antidepressant milk concentration is at its peak. A decision to switch to sertraline from ongoing and effective treatment should be taken only after a scrupulous evaluation of the potential risks and benefits of switching versus continuing the ongoing medication while monitoring the infant carefully.