At the Crossroads between Eating Disorders and Body Dysmorphic Disorders-The Case of Bigorexia Nervosa.

Bigorexia nervosa (BN) is a controversial nosological entity, considered either a feeding/eating disorder (FED) or a subtype of body dysmorphic disorder (BDD). This rapid review aims to explore the characteristic features of BN and identify evidence-based therapeutic interventions for this condition. Three electronic databases (PubMed, Cochrane, and Google Scholar) were searched for relevant information about BN, and 26 reports were reviewed in detail. The results showed that bodybuilders, weightlifters, and other populations involved in athletic activities are the most vulnerable to the onset of this disorder. Patients with BN should also be screened for physical and psychiatric comorbidities and complications, such as anabolic steroid use disorder, physical exercise addiction, and depressive or anxiety disorders. The main differential diagnoses for BN are schizophrenia spectrum disorders, depressive disorders, anxiety disorders, bodily distress disorder, and obsessive-compulsive disorders. Using validated screening instruments is considered very important from a clinical perspective, with the aim of providing early identification of this disorder. Therapeutic interventions for patients with BN are still in the early phases of development, and no specific pharmacological treatment has yet been identified. Since it is similar to the obsessive-compulsive spectrum, cognitive behavioral therapy has been suggested as a useful intervention; however, it has not yet been validated in large-scale clinical trials. In conclusion, based on the reviewed data, clarifying the concept of BN is of practical importance for constructing adequate prevention strategies and validating proper therapeutic interventions.

Current trends and perspectives in the exploration of anorexia athletica-clinical challenges and therapeutic considerations.

Elite athletes are exposed to a considerable amount of physical and psychological stress throughout their entire professional life, but the exploration of the consequences of this stressful regimen on mental health is still in its early stages. Eating disorders (EDs), substance use disorders, and behavioral addictions represent only several domains that are worth more investigation in this vulnerable population, in order to find preventative and therapeutic strategies. The exploration of EDs in athletes is important because this population is very vulnerable to the impact that weight and body shape may have on their professional performances, and epidemiological studies support this concern, i.e., the prevalence of EDs in athletes is significantly higher than in the general population. This article is dedicated to the synthesis of available data regarding a specific pathology reported in elite athletes, i.e., anorexia athletica (AA), based on a narrative reviewing methodology. The information about risk factors, pathophysiology, positive and differential diagnosis, epidemiology, structured evaluation, and treatment of AA have been summarized and future research directions have been highlighted. While tentative diagnostic criteria for AA and a self-administered questionnaire exist, its pathophysiology is still insufficiently explored, and the treatment is not based on good-quality trials. According to the retrieved data, more research targeting the physical and mental health of elite athletes, especially those practicing esthetic sports, is needed, in order to implement adequate screening and early intervention programs. Future studies targeting various sub-populations of elite athletes, i.e., esthetic vs. non-esthetic sports, individuals presenting a history of ED vs. those without such a history, and those practicing individual sports vs. team sports are needed to reach the objective of improving the quality of life in this population.

The complex interplay between psychosocial and biological factors in pregorexia nervosa - a rapid review.

The importance of detecting eating disorders (EDs) during pregnancy cannot be overemphasized, because of the major negative effects this pathology has on both maternal and fetal health. Based on a rapid review including primary and secondary reports, PN may still be considered an elusive diagnosis entity, that partially overlaps with other EDs, either well-defined, like anorexia nervosa, or still in search of their own diagnosis criteria, like orthorexia nervosa. Neurochemical and hormonal factors, psychological and social mechanisms, along with lifestyle changes create a very complex framework for clinicians interested in defining the typical features of pregorexia nervosa (PN). The personal history of EDs is considered one of the most important risk factors for PN. The core diagnostic criteria for this entity are, so far, lack of gaining weight during pregnancy, an excessive focus on counting calories and/or intense physical exercising with a secondary decrease of interest in the fetus's health, lack of acceptance of the change in body shape during pregnancy, and pathological attention for own body image. Regarding the treatment of PN, nutritional and psychosocial interventions are recommended but no specific therapeutic strategies for this disorder have been detected in the literature. Psychotherapy is considered the main intervention for pregnant women with associated EDs and mood disorders, as the pharmacological agents could have teratogenic effects or insufficient data to support their safety in this population. In conclusion, taking into consideration the methodological limitations of a rapid review, data supporting the existence of PN were found, mainly regarding tentative diagnostic criteria, risk factors, and pathophysiological aspects. These data, corroborated with the importance of preserving optimal mental health in a vulnerable population, e.g., pregnant women, justify the need for further research focused on finding specific diagnostic criteria and targeted therapeutic approaches.

Therapeutic management of atypical antipsychotic­related metabolic dysfunctions using GLP­1 receptor agonists: A systematic review.

Metabolic disorders (MDs) like obesity, dyslipidemia, and type 2 diabetes are more frequently observed in patients diagnosed with psychiatric disorders undergoing treatment with antipsychotics, particularly atypical agents, than in the general population. The second generation of antidiabetics (SGAD) has been associated with cardiovascular benefits in large clinical trials which represent an important advantage over first-generation agents and might be of interest in the psychiatric population where multiple risk factors for cardiovascular disease (e.g., smoking, lack of exercise, and lack of healthy diet) are common occurrences. Therefore, this systematic review focused on the evaluation of the glucagon-like peptide-1 receptor agonists (GLP1-RAs), as a representative of the SGAD, to determine whether these agents may be recommended in patients with psychiatric disorders and MDs. For analysis, three electronic databases and clinical trial registers were explored for papers published between January 2000 and November 2022. After applying the inclusion and exclusion criteria, 20 clinical and preclinical trials, therapeutic guidelines, and meta-analyses were reviewed, and clinical recommendations were formulated. The large majority of the reviewed data (nine papers) were graded 'moderate' based on the GRADE criteria. The efficacy and tolerability of liraglutide and exenatide in the management of antipsychotic-induced MDs were supported by evidence of average quality, while the results regarding other GLP-1RAs were not sufficient to formulate a recommendation for their administration in this specific population. Clozapine and olanzapine had the most negative consequences on body weight, glycemic, and lipid metabolism. Therefore, careful monitoring of metabolic parameters is required when these are prescribed. Liraglutide and exenatide may be recommended as augmentative agents to metformin therapy, especially in patients receiving these two atypical antipsychotics, but most of the reviewed data supported the efficacy of GLP-1RAs only during the treatment administration. The two follow-up studies retrieved in the literature reported modest effects after GLP-1RA discontinuation after 1 year; therefore, long-term monitoring of metabolic parameters is required. More research is needed, and three randomized clinical trials are already ongoing, to evaluate the effects of GLP-1RAs in decreasing body weight, but also on other important metabolic variables, such as HbA1c status, fasting glucose levels, and lipid levels in patients receiving antipsychotic treatment.

An integrative model as a step toward increasing the awareness of eating disorders in the general population.

Eating disorders (EDs) represent a contradictory chapter of clinical psychiatry, i.e., although they are associated with significant prevalence and risks in the long term (including vital risk, especially for anorexia nervosa), the therapeutic resources are minimal and based on low-quality data. Another contradiction arose in the last few decades, i.e., a variety of new EDs have been described, either by clinicians or signaled by mass media, but their systematic exploration is progressing very slowly. Entities like "food addiction," "orthorexia nervosa," or "emotional eating disorder" still require intensive exploration in order to find the most accurate diagnostic instruments, diagnosis criteria, prevalence data, vulnerability factors, and therapeutic approaches. This article is focused on integrating into a comprehensive model a variety of EDs not specified or loosely defined by the current international classifications of psychiatric disorders. This framework is intended as an instrument for stimulating clinical and epidemiological research, with potential favorable consequences for therapeutic research. The dimensional model suggested here includes four main categories that accommodate the already recognized EDs (i.e., anorexia nervosa, bulimia nervosa, and binge eating disorder) as well as ten EDs that still need intensive research to find their clinical and pathophysiological characteristics. More good-quality studies are urgently required regarding this topic, based on the mental and physical negative impact these EDs may have in the short and long term, especially in vulnerable populations (e.g., pregnant women, athletes, adolescents, etc.).

State of the Art and Challenges in Epilepsy-A Narrative Review.

Epilepsy is a common condition worldwide, with approximately 50 million people suffering from it. A single seizure does not mean epilepsy; almost 10% of the population can have a seizure during their lifetime. In particular, there are many other central nervous system disorders other than epilepsy in which seizures occur, either transiently or as a comorbid condition. The impact of seizures and epilepsy is, therefore, widespread and easily underestimated. It is estimated that about 70% of patients with epilepsy could be seizure-free if correctly diagnosed and treated. However, for patients with epilepsy, quality of life is influenced not only by seizure control but also by antiepileptic drug-adverse reactions, access to education, mood, employment, and transportation.

The pharmacogenetics of the new-generation antipsychotics - A scoping review focused on patients with severe psychiatric disorders.

Exploring the possible correlations between gene variations and the clinical effects of the new-generation antipsychotics is considered essential in the framework of personalized medicine. It is expected that pharmacogenetic data will be useful for increasing the treatment efficacy, tolerability, therapeutic adherence, functional recovery, and quality of life in patients with severe psychiatric disorders (SPD). This scoping review investigated the available evidence about the pharmacokinetics, pharmacodynamics, and pharmacogenetics of five new-generation antipsychotics, i.e., cariprazine, brexpiprazole, aripiprazole, lumateperone, and pimavanserin. Based on the analysis of 25 primary and secondary sources and the review of these agents' summaries of product characteristics, aripiprazole benefits from the most relevant data about the impact of gene variability on its pharmacokinetics and pharmacodynamics, with significant consequences on this antipsychotic's efficacy and tolerability. The determination of the CYP2D6 metabolizer status is important when administering aripiprazole, either as monotherapy or associated with other pharmacological agents. Allelic variability in genes encoding dopamine D2, D3, and serotonin, 5HT2A, 5HT2C receptors, COMT, BDNF, and dopamine transporter DAT1 was also associated with different adverse events or variations in the clinical efficacy of aripiprazole. Brexpiprazole also benefits from specific recommendations regarding the CYP2D6 metabolizer status and the risks of associating this antipsychotic with strong/moderate CYP2D6 or CYP3A4 inhibitors. US Food and Drug Administration (FDA) and European Medicines Agency (EMA) recommendations about cariprazine refer to possible pharmacokinetic interactions with strong CYP3A4 inhibitors or inducers. Pharmacogenetic data about cariprazine is sparse, and relevant information regarding gene-drug interactions for lumateperone and pimavanserin is yet lacking. In conclusion, more studies are needed to detect the influence of gene variations on the pharmacokinetics and pharmacodynamics of new-generation antipsychotics. This type of research could increase the ability of clinicians to predict favorable responses to specific antipsychotics and to improve the tolerability of the treatment regimen in patients with SPD.

The current state of research for psychobiotics use in the management of psychiatric disorders-A systematic literature review.

The need to find new therapeutic interventions in patients diagnosed with psychiatric disorders is supported by the data suggesting high rates of relapse, chronic evolution, therapeutic resistance, or lack of adherence and disability. The use of pre-, pro-, or synbiotics as add-ons in the therapeutic management of psychiatric disorders has been explored as a new way to augment the efficacy of psychotropics and to improve the chances for these patients to reach response or remission. This systematic literature review focused on the efficacy and tolerability of psychobiotics in the main categories of psychiatric disorders and it has been conducted through the most important electronic databases and clinical trial registers, using the PRISMA 2020 guidelines. The quality of primary and secondary reports was assessed using the criteria identified by the Academy of Nutrition and Diabetics. Forty-three sources, mostly of moderate and high quality, were reviewed in detail, and data regarding the efficacy and tolerability of psychobiotics was assessed. Studies exploring the effects of psychobiotics in mood disorders, anxiety disorders, schizophrenia spectrum disorders, substance use disorders, eating disorders, attention deficit hyperactivity disorder (ADHD), neurocognitive disorders, and autism spectrum disorders (ASD) were included. The overall tolerability of the interventions assessed was good, but the evidence to support their efficacy in specific psychiatric disorders was mixed. There have been identified data in favor of probiotics for patients with mood disorders, ADHD, and ASD, and also for the association of probiotics and selenium or synbiotics in patients with neurocognitive disorders. In several domains, the research is still in an early phase of development, e.g., in substance use disorders (only three preclinical studies being found) or eating disorders (one review was identified). Although no well-defined clinical recommendation could yet be formulated for a specific product in patients with psychiatric disorders, there is encouraging evidence to support further research, especially if focused on the identification of specific sub-populations that may benefit from this intervention. Several limitations regarding the research in this field should be addressed, i.e., the majority of the finalized trials are of short duration, there is an inherent heterogeneity of the psychiatric disorders, and the diversity of the explored Philae prevents the generalizability of the results from clinical studies.

Orphan Drugs in Neurology-A Narrative Review.

BACKGROUND AND AIMS: Orphan diseases, or rare diseases, are defined in Europe as diseases that affect less than 5 out of every 10,000 citizens. Given the small number of cases and the lack of profit potential, pharmaceutical companies have not invested much in the development of possible treatments. However, over the last few years, new therapies for rare diseases have emerged, giving physicians a chance to offer personalized treatment. With this paper, we aim to present some of the orphan neurological diseases for which new drugs have been developed lately. METHODS: We have conducted a literature review of the papers concerning rare diseases and their treatment, and we have analyzed the existing studies for each orphan drug. For this purpose, we have used the Google Scholar search engine and the Orphanet. We have selected the studies published in the last 15 years. RESULTS: Since the formation of the National Organization for Rare Diseases, the Orphan Drug Act, and the National Institutes of Health Office of Rare Diseases, pharmacological companies have made a lot of progress concerning the development of new drugs. Therefore, diseases that until recently were without therapeutic solutions benefit today from personalized treatment. We have detailed in our study over 15 neurological and systemic diseases with neurological implications, for which the last 10-15 years have brought important innovations regarding their treatment. CONCLUSIONS: Many steps have been taken towards the treatment of these patients, and the humanity and professionalism of the pharmaceutical companies, along with the constant support of the patient's associations for rare diseases, have led to the discovery of new treatments and useful future findings.

Efficacy, Tolerability, and Safety of Toludesvenlafaxine for the Treatment of Major Depressive Disorder-A Narrative Review.

The estimated rate of treatment-resistant major depressive disorder (TRD) remains higher than 30%, even after the discovery of multiple classes of antidepressants in the last 7 decades. Toludesvenlafaxine (ansofaxine, LY03005, or LPM570065) is a first-in-class triple monoaminergic reuptake inhibitor (TRI) that has reached clinical use. The objective of this narrative review was to summarize clinical and preclinical evidence about the efficacy, tolerability, and safety of toludesvenlafaxine. Based on the results of 17 reports retrieved in the literature, the safety and tolerability profiles of toludesvenlafaxine were good in all clinical trials, and the pharmacokinetic parameters were well described in the phase 1 trials. The efficacy of toludesvenlafaxine was demonstrated in one phase 2 and one phase 3 trial, both on primary and secondary outcomes. In conclusion, this review highlights the favorable clinical results of toludesvenlafaxine in only two short-term trials that enrolled patients with major depressive disorder (MDD) (efficacy and tolerability were good for up to eight weeks), indicating the need for more good quality, larger-sample, and longer-term trials. Exploring new antidepressants, such as TRI, can be considered a priority for clinical research due to the high rates of TRD, but also due to the significant percentages of relapse in patients with MDD.

Impact of SGLT2 inhibitors on metabolic status in patients with psychiatric disorders undergoing treatment with second­generation antipsychotics (Review).

Metabolic dysfunctions have been reported in patients diagnosed with severe mental illnesses who are undergoing treatment with antipsychotics, especially second-generation agents. Sodium-glucose co-transporter 2 inhibitors (SGLT2Is) and glucagon-like peptide receptor agonists are new-generation antidiabetics whose favourable effects in the treatment of diabetes mellitus in the non-psychiatric population may raise interest in their use in patients presenting with severe mental illnesses and metabolic comorbidities possibly related to the use of antipsychotics. The objectives of this review were to investigate the evidence to support the use of SGLT2Is in this population and to find the most important aspects that need to be addressed by future research. A total of one preclinical trial, two guideline-format clinical recommendations, one systematic review and one case report were found, and their conclusions were analysed. The results support the following conclusions: i) SGLT2Is may be combined with metformin in selected cases of type 2 diabetes mellitus in the context of antipsychotic treatment, as they have been associated with favourable metabolic effects; and ii) data for the recommendation of SGLT2Is as second-line treatment in patients with diabetes mellitus who are also treated with olanzapine or clozapine are supported by very limited preclinical and clinical evidence. Further high-quality, large-scale research is needed in the field of the management of metabolic dysfunctions in patients with severe psychiatric illnesses who undergo treatment with second-generation antipsychotics.

Esketamine for treatment­resistant depression: A review of clinical evidence (Review).

Treatment-resistant depression (TRD) is a challenge for psychiatrists, even after more than seven decades since the first antidepressants were used in clinical practice. Non-monoaminergic-based drugs with antidepressant properties have been developed, but to date, only esketamine and brexanolone have been approved for TRD and postpartum depression, respectively. A narrative review on the efficacy and safety of esketamine in the main categories of depressive disorders has been conducted through four electronic databases (Pubmed, Cochrane, EMBASE and Clarivate/Web of Science) The primary objective of the present review was to find evidence that may support the usefulness of esketamine for patients diagnosed with TRD as well as data about its potential adverse effects in the short and long term. A total of 14 papers were reviewed, and their results support the recommendation of esketamine for treatment of TRD as an add-on to antidepressants, but more data is needed in order to assess its long-term efficacy and safety. It must also be mentioned that there have been a few trials which did not report a significant effect on the severity of depressive symptoms with esketamine in TRD, therefore, caution is indicated for patients initiated on this adjuvant agent. There has been insufficient data to formulate specific guidelines about esketamine administration because evidence about favorable or negative prognostic factors of this treatment has been lacking, and the duration of its administration has not been unanimously accepted. Novel directions for research have been identified, especially in the case of patients with TRD and substance use disorders, geriatric or bipolar depression or in major depression with psychotic features.

Is fecal microbiota transplantation a useful therapeutic intervention for psychiatric disorders? A narrative review of clinical and preclinical evidence.

The therapeutic management of psychiatric disorders is currently confronted with a critical need to find new therapeutic interventions due to the high rates of non-responsivity or low responsivity in the key pathologies, e.g. schizophrenia spectrum disorders, alcohol use disorders, or major depressive disorder. The modulation of intestinal microbiota has been explored in various organic and psychiatric dysfunctions, with different degrees of success. However, this type of intervention may represent a helpful add-on at a conceptual level since it does not associate negative pharmacokinetics interactions, significant adverse events, or risk for non-adherence in the long term. Oral administration of pre-, pro-, or synbiotics, and especially the treatment with fecal microbiota transplantation (FMT), are methods still in their early research phase for patients with psychiatric disorders, therefore an exploration of data regarding the potential benefits and adverse events of FMT was considered necessary. In order to accomplish this purpose, the available results of research dedicated to each category of psychiatric disorders, starting with depressive and anxiety disorders, continuing with schizophrenia, substance use disorders, and finishing with disorders diagnosed during childhood, were presented in this paper. Seven clinical trials, 16 preclinical studies, three meta-analyses/systematic reviews, and six case reports, all of these representing ten distinct categories of psychiatric disorders or manifestations, have been reviewed. Mood disorders, anxiety disorders, and alcohol dependence have been the most extensively investigated clinical entities from the FMT efficacy and tolerability perspective, and reviewed data are generally promising. Based on the current status of research, FMT may be considered a helpful intervention in specific psychiatric pathologies. Still, this review showed that most of the information is derived from entirely preclinical studies. Therefore, clinical trials with sound methodology and more participants are needed to clarify FMT's benefits and risks in psychiatric disorders.

Third-generation antipsychotics in patients with schizophrenia and non-responsivity or intolerance to clozapine regimen: What is the evidence?

Clozapine is considered « the golden standard ¼ for the management of treatment-resistant schizophrenia, but many patients do not present adequate responsivity even to this antipsychotic. If we add the need to strictly monitor the hematologic and cardiometabolic adverse events during each clozapine trial and the difficulty of preserving therapeutic adherence in patients with low insight, residual negative/positive symptoms, or economic challenges, then the necessity of exploring alternative interventions for these patients becomes obvious. Also, in case of intolerance to clozapine or where clozapine did not induce remission, clinicians have to find new ways to help their patients. Switching to other antipsychotics or using these agents as add-ons to clozapine are the main interventions explored in this review, for patients with schizophrenia resistant to clozapine (ultra-resistant schizophrenia, URS). When clozapine intolerance is detected, conversion to another antipsychotic with distinct pharmacologic properties or formulation (e.g., long-acting intramuscular injectable agents, LAI) may be a useful option. Third-generation antipsychotics (TGA) have been selected for their distinct pharmacodynamically profile, which allows, at a theoretical level, their use in combination with clozapine. This narrative review is based on searching four electronic databases, that retrieved 19 primary and secondary reports on aripiprazole (seven case reports or case series presenting 24 patients; nine clinical trials, and three systematic reviews/meta-analyses), two primary reports on brexpiprazole (case report and case series, N = 3 patients), and six primary reports on cariprazine (case reports and case series, N = 14 patients). Based on the information collected from these reports, which included oral and LAI formulations, the TGA most supported by evidence for the augmentation of clozapine is aripiprazole (high-and medium-quality data), followed by cariprazine (low-quality data). Brexpiprazole has not yet been systematically explored for this indication, and in the case of lumateperone, no report could be found. The efficacy of aripiprazole and cariprazine was supported in the domains of positive, negative, and general symptoms, and aripiprazole may positively impact the metabolic profile in patients with URS. Also, adding TGA may lead to a decrease in the dose of clozapine concomitantly administered. More data derived from good quality research are needed in order to confirm the circumstances of TGAs recommendation in patients with URS, either as monotherapy, or added to clozapine.

Therapeutic management of buying/shopping disorder: A systematic literature review and evidence-based recommendations.

The prevalence of buying/shopping disorder (B/SD) has been increasing in the last two decades, and this disorder has a substantial negative impact on general functioning and quality of life. Therefore, a systematic review of the studies dedicated to the efficacy and tolerability of therapeutic interventions, both psychological and pharmacological, might help clinicians to decide on the most evidence-based treatment for these patients. In order to further increase the clinical usefulness of the current review, GRADE-based recommendations were formulated, where enough evidence was found to support such an approach. A number of five electronic databases were searched for single case reports, case series, open-label and double-blind, placebo/active intervention-controlled trials, but other secondary reports (i.e., systematic reviews and meta-analyses) were also included in this analysis. Studies with unspecified designs or those that do not report either qualitatively or quantitively the evolution of B/SD core manifestations were excluded. All data included in the secondary analysis were evaluated using the Joanna Briggs Institute critical appraisal checklists. A total number of 24 manuscripts (i.e., 12 clinical trials, eight case reports, and four reviews) were included. Most of the reviewed studies were of moderate quality, representing a certain limitation of this review and preventing the formulation of high-validity recommendations. Psychotherapy, especially cognitive behavioral therapy (CBT) seems to be the main intervention supported by the current evidence, followed by the combination of antidepressants and CBT, and serotoninergic antidepressants as monotherapy. There is an obvious need to further develop good-quality trials with a more significant number of participants with B/SD and longer follow-up periods.

Investigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents.

Many investigational drugs with antidepressant activity are currently explored in different phases of clinical research, with indications such as major depressive disorder, treatment-resistant major depression, bipolar depression, post-partum depression, and late-life depression. Although the vast majority of the antidepressants in clinical use are based on the monoaminergic hypothesis of depression, recent data supported the launching on the market of two new, non-monoamine-modulating drugs. Esketamine for treatment-resistant major depression and brexanolone for post-partum depression are two exceptions from the monoaminergic model, although their use is still limited by high costs, unique way of administration (only intravenously for brexanolone), physicians' reluctance to prescribe new drugs, and patients' reticence to use them. Glutamatergic neurotransmission is explored based on the positive results obtained by intranasal esketamine, with subanesthetic intravenous doses of ketamine, and D-cycloserine, traxoprodil, MK-0657, AXS-05, AVP-786, combinations of cycloserine and lurasidone, or dextromethorphan and quinidine, explored as therapeutic options for mono- or bipolar depression. Sestrin modulators, cholinergic receptor modulators, or onabotulinumtoxinA have also been investigated for potential antidepressant activity. In conclusion, there is hope for new treatments in uni- and bipolar depression, as it became clear, after almost 7 decades of monoamine-modulating antidepressants, that new pathogenetic pathways should be targeted to increase the response rate in this population.

Investigational Drugs for the Treatment of Depression (Part 1): Monoaminergic, Orexinergic, GABA-Ergic, and Anti-Inflammatory Agents.

Therapeutic management of depression has currently important limitations, and its low efficacy is reflected in high rates of non-response even after multiple trials of antidepressants. Almost two-thirds of the patients diagnosed with major depression who received a 4-6 weeks trial of antidepressant could not reach remission, and more than 30% of these patients are considered treatment-resistant. In bipolar depression, the situation is also discouraging if we analyze the high suicide rate, the risk for the treatment-emergent affective switch when antidepressants are added, the high rate of treatment resistance (up to 25%), and the severe functional impairments associated with these episodes. Therefore, new therapeutic agents are needed, as well as new pathogenetic models for depression. The vast majority of the currently approved antidepressants are based on the monoamine hypothesis, although new drugs exploiting different neurotransmitter pathways have been recently approved by FDA. Brexanolone, an allopregnanolone analog, is an example of such new antidepressants, and its approval for post-partum depression inspired the search for a new generation of neurosteroids and GABA-ergic modulators, with an easier way of administration and superior tolerability profile. Orexin receptors antagonists are also extensively studied for different psychiatric disorders, depression included, in phase II trials. Antiinflammatory drugs, both cyclo-oxygenase 2 inhibitors and biological therapy, are investigated in patients with depressive disorders based on the proven correlation between inflammation and mood disorders in preclinical and clinical studies. Also, a new generation of monoamine-based investigational drugs is explored, ranging from triple reuptake inhibitors to atypical antipsychotics, in patients with major depression. In conclusion, there is hope for new treatments in uni- and bipolar depression, as it became clear, after almost seven decades, that new pathogenetic pathways should be targeted to increase these patients' response rate.

Current Trends and Perspectives in the Immune Therapy for Substance Use Disorders.

Substance use disorders (SUDs) are an extremely challenging category of disorders because of the high rate of relapse, lower life expectancy, important rate of psychiatric and somatic co-morbidity, lack of patients' insight during most of the disease duration, healthcare costs, etc. One of the reasons to consider these disorders very difficult for physicians and the healthcare system is the lack of adequate pharmacological agents with long-term proven efficacy. So far, there are no Food and Drug Administration (FDA) or European Medicines Agency (EMA)-approved treatments for most of the SUDs, except for alcohol use disorder, nicotine use disorder, and opioid use disorder. Immunotherapy has been considered a possible solution to SUDs because it may selectively target a certain drug of abuse, it may have a long-lasting effect (several weeks or months), and it ensures an adequate therapeutic adherence. The objective of this paper was to establish the current stage of research in the field of SUDs vaccines, based on a brief literature review. Vaccines for cocaine and nicotine dependence have reached phase III trials, while other researchers are focusing on passive immunization therapy for methamphetamine use disorder. New generations of vaccines are currently explored, and they are based on superior technologies compared to the first generation of immune therapy (e.g., viral transfer genes, more immunogenic adjuvants, or higher specificity haptens). Therefore, finding immune therapies for substance use disorders SUDs remains a matter of interest, and this approach may be useful for the management of an extremely dangerous and versatile psychiatric pathology.

Case Report: Cariprazine Efficacy in Young Patients Diagnosed With Schizophrenia With Predominantly Negative Symptoms.

Negative symptoms of schizophrenia are among the most invalidating clinical manifestations of this disorder, and they are correlated with poorer prognosis, lower quality of life, and fewer chances for successful social reintegration and professional rehabilitation. Although atypical antipsychotics have been associated with higher efficacy on negative symptoms than typical agents, not all of them are equally effective. Cariprazine is a new D3 and D2 receptor partial agonist, and its high D3 affinity may be useful for decreasing several adverse events (e.g., extrapyramidal symptoms or hyperprolactinemia), and also for increasing this drug's efficacy over negative symptoms. This case series presents three young adults with predominantly negative symptoms during treatment with an atypical antipsychotic, administered in stable dose within the therapeutic range, and for at least 4 weeks prior to the cariprazine switch. These patients (two male and one female, mean age 35.7 years) were diagnosed with schizophrenia, according to the DSM-5 criteria. They were evaluated using Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S), and Global Assessment of Functioning (GAF). Their mean initial values were 80.3 on PANSS, 4.3 on CGI-S, and 48 on GAF. All these patients were already on a treatment with stable doses of atypical antipsychotics (olanzapine 10 mg/day, n = 1, risperidone 6 mg/day, n = 1, and quetiapine 600 mg/day, n = 1). Cross-titration to cariprazine was initiated, from 1.5 mg qd up to 6 mg qd, during a mean period of 2.7 weeks. After 12 weeks of cariprazine 6 mg/day, the positive scale of PANSS was relatively stable compared to baseline, while the negative mean score decreased by 22%. Also, the mean CGI-S improvement was 15.4% and the GAF mean score increased by 17%. The overall tolerability was good, without severe adverse events being reported. Conclusions: Cariprazine is well tolerated and efficient for patients diagnosed with schizophrenia who have significant negative symptoms that impair daily functioning. After 12 weeks cariprazine succeeded in improving negative symptoms, global functioning, and clinical global impression.

Current Status of Evidence for a New Diagnosis: Food Addiction-A Literature Review.

Food addiction is considered an important link for a better understanding of psychiatric and medical problems triggered by dysfunctions of eating behaviors, e. g., obesity, metabolic syndrome, binge eating disorder, or bulimia nervosa. At behavioral level, food addiction has high degrees of similarity with other eating disorders, a phenomenon that creates difficulties in finding specific diagnostic criteria. Food addiction has been also described as "eating addiction" or "eating dependence" by several researchers, who placed the emphasis on the behavior and not on the food itself. High-sodium foods, artificially flavored-foods, rich carbohydrate- and saturated fats-containing foods are triggers for the activation of the same neural pathways, therefore they act similarly to any drug of abuse. Food addiction is considered a disorder based on functional negative consequences, associated distress and potential risks to both psychological well-being and physical health. A clinical scale was validated for the quantification of the eating addiction severity, namely the Yale Food Addiction Severity Scale (YFAS), constructed to match DSM IV criteria for substance dependence. Using this instrument, a high prevalence of food addiction was found in the general population, up to 20% according to a meta-analytic research. The pathogenesis of this entity is still uncertain, but reward dysfunction, impulsivity and emotion dysregulation have been considered basic mechanisms that trigger both eating dysfunctions and addictive behaviors. Genetic factors may be involved in this dependence, as modulators of higher carbohydrate and saturate fat craving. Regarding the existence of potential therapeutic solutions, lorcaserin, antiepileptic drugs, opioid antagonists, antiaddictive agents are recommended for obesity and eating disorders, and they may be intuitively used in food addiction, but clinical trials are necessary to confirm their efficacy. In conclusion, a better understanding of food addiction's clinical profile and pathogenesis may help clinicians in finding prevention- and therapeutic-focused interventions in the near future.