Advances in treatment for postpartum major depressive disorder.

Introduction: Postpartum depressive disorder (PPD) is a burdensome medical condition. To date, only one treatment (Brexanolone) has undergone registrational trials and is approved in the United States with an indication for the treatment of PPD. However, other treatments are prescribed and have been tested for this condition. Herein, the authors review the available scientific evidence pertaining to the somatic treatments of PPD. Areas covered: The authors evaluate the published open-label and randomized controlled trials (RCTs), examine the biological mechanisms of PPD treatments, and evaluate how the available data translates into information that may be useful for clinical practice. Expert opinion: Antidepressants have long been the mainstay of PPD treatment, despite the limited evidence from randomized clinical trials that supports this practice. Brexanolone improves treatment options for women with PPD. However, the relatively burdensome administration and monitoring protocol, along with the high cost of the medication, limit the possibility for an extensive use of this medication. Large, randomized, controlled trials of hormonal treatments in patients with PPD are warranted. Also, treatment with mood stabilizers and/or antipsychotics in women with major depressive disorder, who meet the DSM-5 mixed features specifiers in the post-partum period, should be tested in controlled clinical trials.

Pharmacotherapeutic strategies for treating binge eating disorder. Evidence from clinical trials and implications for clinical practice.

INTRODUCTION: Binge eating disorder (BED) is the most common eating disorder and was newly recognized in 2013 in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). BED is frequently associated with obesity and the metabolic syndrome, as well as with other psychiatric diseases, such as mood (49%), anxiety (41%), and substance use (22%) disorders. BED is highly prevalent and carries a high burden of mental and physical illness and disability. However, BED is frequently under-recognized and under-treated. AREAS COVERED: This paper reviews the main pharmacological treatments for BED and provides an expert opinion based on the available evidence and on the authors' clinical experience with patients affected by BED. EXPERT OPINION: Several medications have proven to be effective for the treatment of BED, including Lisdexamfetamine (LDX), topiramate as well as anti-anxiety and antidepressant medications. To date, LDX is the only FDA approved medication for BED. Consequently, as a general rule, the use of an FDA approved medication should always be preferred. However, when in the presence of concomitant psychiatric conditions such as anxiety or depression, other medications that have proven efficacy in those comorbid conditions can be used and may contextually provide a benefit for BED.

The complex relationship between self-reported 'personal recovery' and clinical recovery in schizophrenia.

Self-reported 'personal recovery' and clinical recovery in schizophrenia (SRPR and CR, respectively) reflect different perspectives in schizophrenia outcome, not necessarily concordant with each other and usually representing the consumer's or the therapist's point of view. By means of a cluster analysis on SRPR-related variables, we identified three clusters. The first and third cluster included subjects with the best and the poorest clinical outcome respectively. The second cluster was characterized by better insight, higher levels of depression and stigma, lowest self-esteem and personal strength, and highest emotional coping. The first cluster showed positive features of recovery, while the third cluster showed negative features. The second cluster, with the most positive insight, showed a more complex pattern, a somewhat 'paradoxical' mixture of positive and negative personal and clinical features of recovery. The present results suggest the need for a characterization of persons with schizophrenia along SRPR and CR dimensions to design individualized and integrated treatment programs aimed to improve insight and coping strategies, reduce stigma, and shape recovery styles.

Older and Newer Strategies for the Pharmacological Management of Agitation in Patients with Bipolar Disorder or Schizophrenia.

BACKGROUND: The management of acute agitation in patients with bipolar disorder or schizophrenia is a multifaceted and dynamic task, which presents unique and complex challenges to healthcare providers. OBJECTIVE: To ascertain and describe which medications are best to use in patients with agitation, affected by bipolar disorder or schizophrenia. METHOD: Selective review of current literature and guidelines referred to the treatment of agitation in individuals affected with bipolar disorder or schizophrenia Results: When possible, the pharmacologic management of agitation should be preceded by a in-depth evaluation of the possible causes of the agitation. The use for of first and second-generation antipsychotic medications, of benzodiazepines and of the newer inhaled antipsychotic loxapine, is reviewed and commented. CONCLUSION: The mainstay of medication treatment of acute agitation should be based on a thotough assessment cause. If agitation is due to delirium or to another physial condition, an attempt to address the underlying causes should be always considered. When agitation is primarily due to schizophrenia or bipolar disorder, antipsychotics and/or benzodiazepines are usually the mainstay of treatment. Newer inhaled formulation of loxapine has shown ability to rapidly reduce the agitation in mild to moderate patients with schizophrenia or bipolar disorder, with a decrease in agitation that was evident since the first assessment, 10 minutes after the first dose.

[The neural bases of social cognition in major depressive disorder: a review]. / La cognizione sociale nel disturbo depressivo maggiore: una rassegna sulle basi neurali.

INTRODUCTION: Major depressive disorder (MDD) is associated with a significant impairment of social and interpersonal functioning. Several neuroimaging studies have evaluated social cognition, i.e. how people with MDD process, store and analyze information about other people and social situations. METHODS: We conducted a focused review and selected manuscript published until August 2016 indexed on PubMed and PsycINFO, searching for the following keywords: "major depressive disorder", "major depression", "unipolar depression", "clinical depression", "fMRI", "emotion comprehension", "emotion perception", "affect comprehension", "affect perception", "facial expression", "prosody", "theory of mind", "mentalizing", "empathy". RESULTS: During depressive episodes, patients with MDD show a difference pattern of neural response during emotion processing, compared to healthy controls. Many studies show that those alterations disappear once the acute episodes remit. However, other studies show that the alterations may persist during remission periods. Limits. The studies evaluate only one component of social cognition and not all studies include a control group. CONCLUSIONS: Neurobiological research supports a role of social cognition deficits in MDD, especially for what pertains interpersonal functioning, this suggesting the need for further research and the possibility for treatment implications.

Personal resources and depression in schizophrenia: The role of self-esteem, resilience and internalized stigma.

Depression in schizophrenia represents a challenge from a diagnostic, psychopathological and therapeutic perspective. The objective of this study is to test the hypothesis that resilience and self-stigma affect depression severity and to evaluate the strength of their relations in 921 patients with schizophrenia. A structural equation model was tested where depression is hypothesized as affected by resilience, internalized stigma, gender and negative symptoms, with the latter two variables used as exogenous covariates and the former two as mediators. The analysis reveals that low resilience, high negative symptoms, female gender were directly associated with depression severity, and internalized stigma acted only as a mediator between avolition and resilience, with similar magnitude. The cross-sectional study design and the variable selection limit the generalizability of the study results. The model supports a complex interaction between personal resources and negative symptoms in predicting depression in schizophrenia. The clinical implication of these findings is that personal resources could be a significant target of psychosocial treatments.

Clinical trial methodology to assess the efficacy/effectiveness of long-acting antipsychotics: Randomized controlled trials vs naturalistic studies.

Schizophrenia presents unique difficulties in clinical trial design associated with the condition's variable presentation and clinical course, and multiple features influencing affect, cognition, volition and perception. Randomized controlled trials (RCTs) are explanatory studies using a carefully selected patient population, predefined assessment intervals and, generally, symptom-focused endpoints. Naturalistic studies are pragmatic, with no active intervention, and outcomes that are generally those used in clinical practice (e.g. hospitalization, relapse rate). Both naturalistic studies and RCTs have pros and cons, making it difficult for physicians in clinical practice to apply research findings to their own treatment decisions. The choice of clinical trial design can have a significant impact on the comparative effectiveness or efficacy of drugs. This is particularly true for studies comparing long-acting injectable (LAI) antipsychotics with oral antipsychotics in schizophrenia, in which RCTs generally show no benefit for LAIs over oral drugs, whereas observational studies do. The more pragmatic the study design, the more likely it is to show a benefit for LAIs versus oral therapy. This article reviews the pros and cons of different study types, using published examples. Criteria are outlined to help physicians design appropriate prospective studies in schizophrenia including the relevant pragmatic and/or explanatory features, as required.

[Neural basis of social cognition in bipolar disorder]. / Le basi neurali della cognizione sociale nel disturbo bipolare.

AIM: This article review studies social and interpersonal functioning in patients with bipolar disorder (BD), and reports on the neurobiological underpinnings of the dysfunctions in emotion recognition, i.e. one of the main domains of social cognition. METHODS: A bibliographical research of controlled studies from 1967 to 2015 was completed in PubMed and PsycINFO using the keywords: "fMRI", "emotion comprehension", "emotion perception", "affect comprehension", "affect perception", "facial expression", "prosody", "theory of mind", "mentalizing", "attributional style", "social perception", "empathy" and "bipolar disorder" or "unipolar depression". RESULTS: Limbic hyperactivity, with a lack of appropriate cortical control, has been reported in subjects with BD during social interactions. This is particularly evident during the acute affective episodes but may persist during the euthymic phases. DISCUSSION: Deficits in emotion regulation, including neural systems implicated both in voluntary and automatic emotion regulatory subprocesses, are present in DB, particularly for what pertains to social interactions and interpersonal functioning. CONCLUSIONS: Patients with bipolar disorder may present a dysfunction in the cortical ability to modulate the limbic system, which may show hyperactivity during social interactions. More studies are needed, including studies to evaluate treatment implications.

Starting aripiprazole long-acting-once-a-month early in treatment: why, how and for whom? Expert consensus and practical recommendations by a panel of Italian clinicians.

INTRODUCTION: Aripiprazole long acting once-monthly (AOM) is approved for the treatment of schizophrenia in adults. Despite recent evidence of AOM efficacy in the acute treatment of schizophrenia, it is recommended that AOM should be started once the acute symptoms are controlled and patients are stabilized. However, there currently are no definitive guidelines exactly describing when a patient is to be considered stabilized enough to start AOM and which the patients are for whom an early AOM start is to be preferred. Areas covered: A panel of Italian clinicians experienced with real world use of AOM met to discuss the scenarios where an early (i.e., immediately after controlling the acute symptoms) start of AOM may be suggested. Real life clinical experiences were shared and a consensus was reached. Expert opinion: There are cases when the risks/benefits ratio suggests to start AOM early, i.e. immediately after the acute symptoms have been stabilized, as opposed to starting it several days/weeks after the stabilization of acute symptoms. Clinical pearls, guidelines and opinions are provided.

[Trazodone Contramid® in clinical practice: personalizing antidepressant intervention]. / Trazodone Contramid® nella pratica clinica: strategie per la personalizzazione dell'intervento antidepressivo.

AIM: This paper examines the use of Trazodone Contramid® in major depressive disorder (MDD), with a focus on practical guidance regarding real world challenges. The paper includes clinical case reports, developed for didactic reasons, which detail the practical management with Trazodone Contramid® of patients with MDD and either insomnia or anxiety or dementia or isolated (ipo)manic symptoms, which often fulfill the criteria for a diagnosis of MDD with with anxious distress or MDD with mixed features, according to the new DSM-5 classification. METHODS: A literature search was performed using appropriate keywords to identify studies where any formulation of trazodone was used. The reference lists of those studies identified were cross-referenced for additional studies. RESULTS: Based on the literature search and our clinical experience, we report that trazodones may be particularly useful in those forms of depression with comorbid anxiety or insomnia or isolated manic symptoms or dementia. DISCUSSION: Trazodone has proven an effective medication in patients with MDD but has not been extensily studied in terms of its efficacy for specific phenotypes of depression. Hereby we report that Trazodone Contramid® may be particularly effective in those forms of MDD that are characterized by comorbid insomnia, and/or anxiety, and/or isolated manic symptoms and/or dementia. These forms of depression are very common and a thorough knowledge of Trazodone Contramid® pharmacological properties will aid choosing and managing this medication at the best. CONCLUSIONS: Trazodone contramid is a relatively new formulation of trazodone, which has proven effective in MDD, particularly in those difficult to treat cases of MDD characterized by symptoms such as insomnia, anxiety, dementia or (ipo)manic symptoms. The once-a-day formulation of trazodone may provide a combination of improved tolerability and efficacy over other antidepressants and over the conventional immediate-release formulation of the same medication.

Switching long acting antipsychotic medications to aripiprazole long acting once-a-month: expert consensus by a panel of Italian and Spanish psychiatrists.

INTRODUCTION: Aripiprazole long acting once-monthly (AOM) is a long acting atypical antipsychotic with proven efficacy in schizophrenia and with a pharmacological and a side effect profile that is different from other antipsychotics. These and other characteristics make AOM a possible alternative in patients requiring a change in long acting antipsychotic treatment due to issues such as lack of efficacy or persistent side effects. Both clinical and pharmacological factors should be considered when switching antipsychotics, and specific guidelines for long acting antipsychotic switching that address all these factors are needed. AREAS COVERED: A panel of Italian and Spanish experts in psychiatry met to discuss the strategies for the switch to AOM in patients with schizophrenia. Real life clinical experiences were shared and the clinical strategies to improve the likelihood of success were discussed. EXPERT OPINION: Due to its specific pharmacological and tolerability profile, AOM represents a suitable alternative for patients with schizophrenia requiring a switch to a new LAI treatment because of lack of efficacy or persistent side effects from another LAI. Possible strategies for the switch to AOM are presented in this expert consensus paper in an attempt to provide guidance throughout the entire switching process.

Off-Label Trazodone Prescription: Evidence, Benefits and Risks.

Although trazodone is approved and marketed in most countries worldwide for the sole treatment of Major Depressive Disorder, the use for this medication is very common for many other conditions, such as primary or secondary insomnia, Generalised Anxiety Disorder, Panic Disorder, Post-Traumatic Stress Disorder and Obsessive- Compulsive Disorder. Other, not officially approved, uses of trazodone include: the treatment of bulimia, benzodiazepine and/or alcohol dependence or abuse, fibromyalgia, degenerative diseases of the central nervous system such as dementia and other organic disorders, schizophrenia, chronic pain, and diabetic neuropathy. In addition, due to its 5HT2A receptor antagonistic action, trazodone may be used to prevent the occurrence of initial and long-term side effects of SSRI, such as anxiety, insomnia and sexual dysfunction. Despite the favorable clinical experience and the encouraging results from the studies that have tested the efficacy of trazodone for some of its off-label indications, it is paramount that large, randomized and controlled clinical trials be conducted in the near future to evaluate which of the many off-label indications are supported by a strong scientific evidence.