Treatment Of Psychotic Disorders Research Articles

Clinical effects of CYP2D6 phenoconversion in patients with psychosis.

Pharmacogenetics is considered a promising avenue for improving treatment outcomes, yet evidence arguing for the use of pharmacogenetics in the treatment of psychotic disorders is mixed and clinical usefulness is under debate. Many patients with psychosis use multiple medications, which can alter the metabolic capacity of CYP enzymes, a process called phenoconversion. In clinical studies, treatment outcomes of drugs for psychosis management may have been influenced by phenoconversion. Here we evaluate the impact and predictive value of CYP2D6 phenoconversion in patients with psychotic disorders under pharmacological treatment. Phenoconversion-corrected phenotype was determined by accounting for inhibitor strength. Phenoconversion-corrected and genotype-predicted phenotypes were compared in association with side effects, subjective well-being and symptom severity. Phenoconversion led to a large increase in poor metabolizers (PMs; 17-82, 16% of sample), due to concomitant use of the serotonin reuptake inhibitors fluoxetine and paroxetine. Neither CYP2D6-predicted nor phenoconversion-corrected phenotype was robustly associated with outcome measures. Risperidone, however, was most affected by the CYP2D6 genotype. Polypharmacy and phenoconversion were prevalent and accounted for a significant increase in PMs. CYP2D6 may play a limited role in side effects, symptoms and well-being measures. However, due to the high frequency of occurrence, phenoconversion should be considered in future clinical trials.

Virtuell virkelighet, virkelig mestring: Virtual Reality som verktøy i behandling av psykoselidelser

Virtual reality (VR) is emerging as an innovative tool in psychotherapy. In this article, we review the evidence base for the use of VR in therapy, focusing on the treatment of psychotic disorders. We present a fictional case study based on real-life patient pathways from several psychosis treatment units at Oslo University Hospital, showing how VR can be used to address anxiety and avoidance behaviours in patients with psychotic disorders. Furthermore, we introduce RecoVRy, a novel Norwegian intervention combining VR and artificial intelligence (AI) to help individuals with psychotic disorders manage everyday anxiety. Although integrating VR and AI holds considerable potential, we also discuss challenges related to privacy and ethical considerations. We conclude that although VR therapy probably does not represent a universal solution, the technology constitutes a valuable supplement that can enrich therapeutic practices and potentially contribute to significant health and socioeconomic savings. Finally, we emphasise the need for further research to fully realise this potential. Keywords: Virtual reality, VR, virtual reality exposure therapy, VRET, artificial intelligence, AI, psychosis, schizophrenia

Cannabidiol as an antipsychotic drug.

Cannabidiol (CBD) is a major phytocannabinoid in the Cannabis sativa plant. In contrast to Δ9-tetrahydrocannabinol (THC), CBD does not produce the typical psychotomimetic effects of the plant. In addition, CBD has attracted increased interest due to its potential therapeutic effects in various psychiatric disorders, including schizophrenia. Several studies have proposed that CBD has pharmacological properties similar to atypical antipsychotics. Despite accumulating evidence supporting the antipsychotic potential of CBD, the mechanisms of action in which this phytocannabinoid produces antipsychotic effects are still not fully elucidated. Here, we focused on the antipsychotic properties of CBD indicated by a series of preclinical and clinical studies and the evidence currently available about its possible mechanisms. Findings from preclinical studies suggest that CBD effects may depend on the animal model (pharmacological, neurodevelopmental, or genetic models for schizophrenia), dose, treatment schedule (acute vs. repeated) and route of administration (intraperitoneal vs local injection into specific brain regions). Clinical studies suggest a potential role for CBD in the treatment of psychotic disorders. However, future studies with more robust sample sizes are needed to confirm these positive findings. Overall, although more studies are needed, current evidence indicates that CBD may be a promising therapeutic option for the treatment of schizophrenia.

Seven decades of antipsychotic drugs: Why is the life of Australians with schizophrenia still so suboptimal?

The advent of dopamine (D2) receptor-blocking medications over 70 years ago, ushered in a new era of biological treatment for schizophrenia. However, we argue that little subsequent progress has been made in translating this into fulfilled and fulfilling lives for people with schizophrenia. This Viewpoint asks why this is the case, and suggests ways forward for capitalising on extant and emerging new treatments for psychotic disorders, to the betterment of the lives of people living with schizophrenia.

Dysregulation of Microbiota in Patients With First-Episode Psychosis Is Associated With Symptom Severity and Treatment Response

BackgroundThe gut microbiome has been implicated in the pathogenesis of mental disorders where the gut-brain axis acts as a bidirectional communication network. MethodsHerein, we investigated the compositional and functional differences of gut microbiome between patients with first-episode psychosis (FEP) (n = 26) and healthy control participants (n = 22) using whole-genome shotgun sequencing. In addition, we assessed the oral microbiome in patients with FEP (n = 13) and listed their taxonomic diversity. ResultsOur findings suggest that there is a dysbiosis of gut microbiota in patients with FEP. Relative abundance of Bifidobacterium adolescentis, Prevotella copri, and Turicibacter sanguinis was markedly increased (linear discriminant analysis scores [log10] > 1, and Mann-Whitney U test; false discovery rate–adjusted p values < .05) in the FEP group compared with the healthy control participants. Pathway analysis indicated that several metabolic pathways, particularly deoxyribonucleotide biosynthesis, branched-chain amino acid biosynthesis, tricarboxylic acid cycle, and fatty acid elongation and biosynthesis, were dysregulated in the FEP group compared with the healthy control group. In addition, this preliminary study was able to identify specific gut microbes (at baseline) that were predictive of weight gain in the FEP group at a 1-year follow-up. Bacteroides dorei, Bifidobacterium adolescentis, Turicibacter sanguinis, Roseburia spp., and Ruminococcus lactaris were positively associated (eXtreme gradient boosting, XGBoost regression model, Shapley additive explanations, R2 = 0.82) with weight gain. ConclusionsOur findings may suggest the involvement of gut microbiota in the pathogenesis of psychosis. The benefit of modulation of the gut microbiome in the treatment of psychotic disorders should be explored further.

Trait Mindfulness in Psychotic Disorders: Dimensions Predicting Symptoms, Cognition, and Functional Outcome

Mindfulness-based treatments are efficacious for psychotic disorders (PD). However, which components of mindfulness (i.e., attentive monitoring and nonjudgmental acceptance) are most relevant treatment targets is unclear. Further, there is a dearth of literature examining clinical correlates of mindfulness in people with PD. The present study aimed to examine group differences and clinical correlates of mindfulness in people with PD. We hypothesized that PD would report lower monitoring and acceptance than CN and that mindfulness components would be associated with symptoms including dysfunctional beliefs, alexithymia, neurocognitive ability, positive symptoms, and mood symptoms. Groups included individuals with PD (n = 54) and nonpsychiatric controls (n = 55). Participants completed self-report measures of mindfulness and related constructs and clinical interviews of symptoms. Results of ANOVA models indicated that global mindfulness was lower in PD relative to CN, with greatest differences evident for acceptance in the affective psychosis group. Regression models found that greater monitoring was associated with improved neurocognitive performance, while acceptance was associated with lower defeatist beliefs, alexithymia, and depression/anxiety symptoms. Results highlight the importance of targeting acceptance in the psychosocial treatment of PDs, especially for those with mood symptoms.

The impact of cannabidiol treatment on resting state functional connectivity, prefrontal metabolite levels and reward processing in recent-onset patients with a psychotic disorder

The first clinical trials with cannabidiol (CBD) as treatment for psychotic disorders have shown its potential as an effective and well-tolerated antipsychotic agent. However, the neurobiological mechanisms underlying the antipsychotic profile of CBD are currently unclear. Here we investigated the impact of 28-day adjunctive CBD or placebo treatment (600 mg daily) on brain function and metabolism in 31 stable recent-onset psychosis patients (<5 years after diagnosis). Before and after treatment, patients underwent a Magnetic Resonance Imaging (MRI) session including resting state functional MRI, proton Magnetic Resonance Spectroscopy (1H-MRS) and functional MRI during reward processing. Symptomatology and cognitive functioning were also assessed. CBD treatment significantly changed functional connectivity in the default mode network (DMN; time × treatment interaction p = 0.037), with increased connectivity in the CBD (from 0.59 ± 0.39 to 0.80 ± 0.32) and reduced connectivity in the placebo group (from 0.77 ± 0.37 to 0.62 ± 0.33). Although there were no significant treatment effects on prefrontal metabolite concentrations, we showed that decreased positive symptom severity over time was associated with both diminishing glutamate (p = 0.029) and N-acetyl-aspartate (NAA; neuronal integrity marker) levels (p = 0.019) in the CBD, but not the placebo group. CBD treatment did not have an impact on brain activity patterns during reward anticipation and receipt or functional connectivity in executive and salience networks. Our results show that adjunctive CBD treatment of recent-onset psychosis patients induced changes in DMN functional connectivity, but not prefrontal metabolite concentrations or brain activity during reward processing. These findings suggest that DMN connectivity alteration may be involved in the therapeutic effects of CBD.

The use of digital psychosocial intervention (DIALOG+) via a mental health community team at the University Clinic of Psychiatry - Skopje

IntroductionThe University Clinic of Skopje – Skopje was part of two Horizon 2020 projects – IMPULSE and RECOVER-e that finished in December 2021. The advances in the field of community mental health in the capital of Skopje, the idea to combine the best aspects of the aforementioned projects and the need of continual implementation and research on an evidence-based community-based service delivery model for recovery-oriented care led to this study which aims to improve functioning, quality of life, and mental health outcomes for people with severe and enduring mental ill health, such as schizophrenia, bipolar disorder, severe depression.Objectives The objectives of the study are: - to design, implement and evaluate recovery-oriented care for people with severe mental illness in community settings using a psychosocial digital intervention - DIALOG+;- to recognize the value of experiential knowledge through inclusion of peer experts as members of community mental health teams;- to develop scale-up plans for national decision-makers, as informed by the intervention’s implementation and impact, for sustained implementation and scale up after the research study’s timeline.- to improve the conditions of people suffering from psychotic disorders and to overcome financial barriers encountered in the treatment of psychotic disorders in N. Macedonia.MethodsDIALOG+ represents an affordable and effective intervention which has already demonstrated positive outcomes in previous research. This study involves the use of the DIALOG+ intervention during home visits, so that patients themselves can decide which aspects of their life that they would like to discuss and work on improving. DIALOG+ lets them rate 12 domains that are related to quality of life, such as physical health, relationships and employment. Patient decide which of these they would like to discuss in detail during the meeting. There is then a 4-step approach to help improve this aspect of their life, using the principles of solution-focused therapy. Researchers will collect information about demographic characteristics, quality of life, and symptoms in patients taking part in the study through the administration of questionnaires and clinical scales.ResultsThe study is still in phase of completion. The results will be shown at the EPA Congress 2023.Conclusions Having the previous positive outcomes from IMPULSE and RECOVER-e, with this combined approach we expect even more improvement in functioning and better quality of life in patients suffering from severe and enduring mental ill health.Disclosure of InterestNone Declared

The relation between electroconvulsive therapy and dopamine

IntroductionThe use of electroconvulsive therapy (ECT) as a treatment for psychotic disorders is well-documented and effective. Despite the fact that ECT is often used, the precise neurobiological mechanisms supporting its effectiveness are still incompletely understood. Over the pastyears, extensive research on primates, rodents, and humans has begun to clarify the effects of electroconvulsive seizures (ECS) and ECT on neurotransmission systems such the dopaminergic system.ObjectivesThe aim of this paper is to search evidence in the literature regarding the effects of ECT on the dopamine system.MethodsIn order to write this article, we searched for information in the most important scientific articles from the Google Scholar and Pubmed databases regarding the effects of ECT on the dopaminergic system.ResultsECT and electroconvulsive shock are linked to enhanced dopamine release and dopamine receptor modification. Human studies show that ECT activates the dopamine system. In a study by Rudorfer et al., it was discovered that ECT increased the amount of homovanillic acid (HVA), a marker of dopamine turnover, in the cerebrospinal fluid (CRF). One important study indicates that monkeys given a brief clinical course of ECT (six sessions only) exhibit significant changes in dopaminergic presynaptic neurotransmission, with baseline function returning to quadratic (‘inverted U’ shape) by six weeks of the last ECT treatment. According to single-unit electrophysiological methods, repeated electroconvulsive shock to rats causes a subsensitivity of dopamine autoreceptors in the substantia nigra. Since effects identical to those reported with repeated treatment were also detected when a single electroconvulsive shock was followed by an acceptable treatment-free interval, this decreased sensitivity is time-dependent.ConclusionsThe results support the idea that ECT boosts the dopamine system and can be an effective strategy in the management of psychotic disorders.Disclosure of InterestNone Declared

Current evidence for various inpatient psychotherapy programs in the treatment of psychoses-A narrative review article

The analysis of the efficacy of evidence-based psychotherapy for patients with psychotic disorders has mostly been carried out in the outpatient field. In the inpatient field the efficacy is sometimes difficult to assess due to different healthcare systems. The aim of this narrative review is to summarize international guidelines and meta-analyses on the efficacy of inpatient psychotherapeutic treatment strategies for patients with psychotic disorders. Based on this, recommendations for disorder-specific ward concepts for acute and postacute fields are formulated. The German S3 guidelines, international guidelines, current meta-analyses and primary studies on psychological interventions in the treatment of psychotic disorders were included. Based on the results, recommendations for the inpatient psychotherapeutic treatment in various phases of treatment were formulated (acute phase and postacute phase). In the acute phase a combination of cognitive behavioral therapy (CBTp) in the individual setting and family interventions in the group setting as well as metacognitive training (MCT acute) is effective and recommended. In the postacute phase, in addition to individual and group CBTp and family interventions, psychoeducation, social skills training and cognitive remediation have been shown to be effective and are recommended. The suggested recommendations for concrete interventions in various treatment phases and the evidence base are critically discussed and recommendations for the structure of wards are presented.

Assessment of Plasma Glucose and Lipid Profile Dysregulation among Patients on Antipsychotics in Sokoto

Background: Antipsychotic drugs used in the treatment of psychotic disorders have been implicated in negative effects on the blood glucose and lipid profile levels of patients. Methods: We studied the anthropometric parameters and then the plasma glucose and lipid profile levels of one hundred and seventy-two (172) patients between the ages of 18 and 45 years; who are on various oral antipsychotics. Also, forty (40) treatment-naïve psychiatric patients and forty (40) healthy controls were included in the study. The results were analysed using standard methods. Results: The mean plasma glucose level was significantly higher (p&lt;0.05) in psychiatric patients on oral antipsychotic drugs compared to controls. The mean plasma glucose level of treatment-naïve psychiatric patients was also significantly higher (p&lt;0.05) compared to that of healthy controls. Furthermore, there was a significant increase in plasma glucose levels of patients on second-generation antipsychotic drugs compared to those on first-generation antipsychotic drugs. The lipid profile of patients on antipsychotic drugs showed a similar trend. There were significant increases in the plasma levels of Total Cholesterol (TC), Low-Density Lipoprotein (LDL), Triglycerides (TG) and a significant decrease in the plasma level of High-Density. However, the plasma TG levels were significantly higher in the typical antipsychotic drugs group. Lipoprotein (HDL) levels of individuals that were on antipsychotics were significantly decreased when compared to healthy controls Conclusion: The lipid profile and plasma glucose concentration were altered by oral antipsychotic drugs in Sokoto, Nigeria. Therefore, it may be clinically expedient to vigorously assess the plasma glucose and lipid profile levels of all patients that are on oral antipsychotic drugs and interventions planned as appropriate. Keywords: Antipsychotic drugs, lipid profile, glucose, Cholesterol, Lipoprotein

Dealing with Psychotic Symptoms at Digital Distance

The EPA Guidance on the Quality of eMental health interventions in the treatment of psychotic disorders (1), based on systematic literature review, found strong evidence that web- and mobile based interventions for people with schizophrenia and/or other psychotic disorders are feasible and acceptable both for patients and caregivers. There was moderate evidence that eMental health interventions may improve specific elements of mental healthcare processes, such as shared-decision-making, symptom monitoring, disease management, information provision, empowerment, and there was preliminary evidence that they may also improve outcomes by fostering symptom reduction and treatment adherence. E-mental health interventions hold promise to shape the future of mental healthcare delivery through increasing service accessibility, reducing stigma and self-stigma, and providing timely and flexible support to individuals with psychotic disorders and their caregivers. Nevertheless, it is important to also consider other aspects such as the lack of ethical guidelines and quality assurance mechanisms, and the need to analyse the legal frameworks about eMental health in different nations when developing and implementing eMental health interventions. We did not identify ethical guidelines or quality assurance systems specifically developed for eMental health interventions targeting people with psychotic disorders. E-mental health interventions are efficacious to increase mental health literacy. We also found preliminary evidence that eMental health interventions are efficacious to treat psychotic disorders. Recent overviews (2) are coming to similar conclusions. Future research needs to provide better controlled, sufficiently powered studies to provide definite answers to open questions. Gaebel et al., 2016, DOI 10.1007/s00406-016-0677-6 Donahue, Rodriguez, Shore, 2021, doi.org/10.1007/s11920-021-01242-yDisclosureNo significant relationships.

Hospital readmissions in the group of users on the Flexible Assertive Community Treatment – experiences from RECOVER E Montenegro samples

IntroductionAs a part of Horizon 2020 program, RECOVER-E project activities were initiated in Montenegro in 2018. The initial step involved a thorough situation analysis of the setting and circumstances of treatment of users with severe mental health illnesses, followed by the establishment of the community mental health team (CMHT) within the Special Psychiatric Hospital Kotor. The CMHT became responsible for the treatment of a group of clients with severe mental health illnesses, based on the principles of „Flexible Assertive Community Treatment (FACT – A Dutch model).ObjectivesThe main objective of this research was to establish whether there were substantial differences regarding the hospital readmissions in the group of patients treated by the CMHT, compared to usual mental health care in Montenegro.MethodsWithin the RECOVER-E project, a sample of 202 patients, users of mental health services, were recruited in Montenegro. Patients were randomized into two similar-sized groups - intervention group, whose treatment was managed by the multidisciplinary CMHT, and control group where treatment as usual was continued. To estimate and follow-up the frequency of hospital readmissions, medical documentation was used.ResultsPatients in the intervention group had less hospital days during the 18 months follow-up period. However, the differences between two groups regarding number of readmissions, and total length of hospital days were not statistically significant measured by independent T test.ConclusionsThis study showed that CMHT care could reduce the total length of hospital days during the treatment of psychotic disorders even dough during the COVID 19 pandemic and lock down measuresDisclosureNo significant relationships.

Ethical considerations in the treatment of chronic psychosis in a periviable pregnancy

Background: Treatment of psychotic disorders in pregnancy is often ethically and clinically challenging, especially when psychotic symptoms impair decision-making capacity. There are several competing ethical obligations to consider: the ethical obligation to maternal autonomy, the maternal and fetal beneficence-based obligations to treat peripartum psychosis, and the fetal beneficence-based obligation to minimize teratogenic exposure. Objective: This article outlines an ethical framework for clinical decision-making for the management of chronic psychosis in pregnancy, with an emphasis on special considerations in the previable and periviable period. Case Presentation: A 31-year-old gravida 2, para 1 with intrauterine pregnancy at 12 weeks and 4 days gestation was brought to the emergency department by her husband seven months after delivering her first child, due to sudden onset of behavioral changes that included self-isolation, not eating, and not taking care of her child. Her past medical history included hypothyroidism and inflammatory bowel disease, but no prior psychiatric illness. After being admitted to the psychiatric hospital, she continued to have poor oral intake and weight loss despite initial inpatient treatment with antipsychotics, levothyroxine, and discontinuation of corticosteroids. Her pregnancy was also complicated by the diagnosis of multiple fetal anomalies at 20 weeks gestation, when the fetus was periviable. Conclusions: For previable or periviable pregnancies, the patient and/or surrogate should decide whether to pursue prenatal genetic screening and invasive diagnostic testing, as well as whether to continue or terminate the pregnancy. When the choice is made to continue the pregnancy, initiation of long-term psychiatric treatment (including medications with potential adverse fetal effects) should be based on shared decision-making between the physician and the patient and/or surrogate. Although some pharmacologic interventions may have potential adverse effects on the developing fetus, the use of psychotropic medications can be ethically justified, even if the patient herself does not have the capacity to consent and requires a surrogate, when the goal is to restore maternal autonomy and minimize the risks of maternal and fetal harm from untreated psychiatric illness.

Structural Racism and Inequities in Incidence, Course of Illness, and Treatment of Psychotic Disorders Among Black Americans.

Psychotic disorders (e.g., schizophrenia, schizoaffective disorder) are a leading cause of morbidity and premature mortality and an overlooked health inequity in the United States. European data indicate inequities in incidence, severity, and treatment of psychotic disorders, particularly for Black communities, that appear to be primarily attributable to social adversities. The dominant US narrative is that any observed differences are primarily a result of clinician bias and misdiagnosis. We propose that employing the framework of structural racism will prompt European and US research to converge and consider the multifaceted drivers of inequities in psychotic disorders among Black Americans. In particular, we describe how historical and contemporary practices of (1) racialized policing and incarceration, and (2) economic exploitation and disinvestment, which are already linked to other psychiatric disorders, likely contribute to risks and experiences of psychotic disorders among Black Americans. This framework can inform new strategies to (1) document the role of racism in the incidence, severity, and treatment of psychotic disorders; and (2) dismantle how racism operates in the United States, including defunding the police, abolishing carceral systems, and redirecting funds to invest in neighborhoods, housing, and community-based crisis response and mental health care. (Am J Public Health. 2022;112(4):624-632. https://doi.org/10.2105/AJPH.2021.306631).

One-Month versus Three-Month Formulation of Paliperidone Palmitate Treatment in Psychotic Disorders: Patients', Relatives', and Mental Health Professionals' Perspectives.

PurposePaliperidone palmitate is the only available long acting injectable (LAI) antipsychotic with a monthly and three-monthly formulation. LAIs may help battle non-adherence. Studies about the experiences of switching from the monthly (PP1M) to the three-monthly formulation (PP3M) of paliperidone are scarce. Therefore, the aim of this study is to evaluate the perspectives of patients, relatives, and mental health professionals on PP3M compared with PP1M.Material and MethodsThis was a multicenter, retrospective, non-interventional one-time questionnaire survey among patients with psychotic disorders who switched from PP1M to PP3M (n = 38), their relatives (n = 13) and mental health professionals (n = 38). General satisfaction and (un)desired effects were measured using the Medication Satisfaction Questionnaire (MSQ) and the Subjects’ Reaction to Antipsychotics (SRA), respectively. Additional questionnaires assessed socio-demographic variables, preference, effectiveness, side-effects, and confidence in PP3M compared to PP1M.ResultsMean number of received PP3M injections was 4.2 (SD 2.5). The three study groups reported a high level of confidence in PP3M. High general satisfaction rates about PP3M among patients (69%) and mental health professionals (95%) were reported. The majority of patients, relatives, and mental health professionals reported similar or in some cases even greater effectiveness and similar or in some cases even less side-effects of PP3M compared to PP1M. Sixty-seven percent of the relatives reported less concerns about non-adherence after switching to PP3M.ConclusionMost patients, relatives, and mental health professionals prefer PP3M over PP1M. The positive attitudes of all parties may facilitate the more frequent use of PP3M and potentially the clinical outcomes.

La psicosi e i disturbi psicotici nei bambini e negli adolescenti

Psychosis can present a variety of symptoms such as hallucinations, delusions, catatonia, thought and speech disorganization, alogia, avolition and general functional decline. Transient psychotic symptoms are not uncommon during development and are not always indicative of psychopathology. Psychosis can be a manifestation of a schizophrenia spectrum disorder, or occur in the context of a mood disorder, such as major depression or bipolar mania. It can also be due to substance abuse or certain medical conditions, such as the NMDA encephalitis. Most cases of schizophrenia start between 15 and 25 years of age, while an onset under age 13 is rare. Schizophrenia tends to have an insidious onset with many months of subsyndromal and non-specific symptoms prior to the first openly psychotic episode. Repeated use of cannabis in youth increases the risk of psychosis, since the developing brain is especially sensitive to the psychoactive effects of tetrahydrocannabinol. As the duration of untreated psychosis predicts worse functional outcomes over time, a prompt recognition and early treatment of psychotic disorders has high clinical relevance. To this end, a close collaboration between paediatricians and child and adolescent neuropsychiatrists is crucial.

Adjunctive use of metformin in the treatment of atypical antipsychotic-induced weight gain

Introduction. Atypical antipsychotics are the gold standard in the treatment of psychotic and other mental disorders due to their efficacy and tolerability. However, the relatively frequent occurrence of antipsychotic-induced metabolic syndrome has encouraged research into possible solutions to this problem, including the adjunctive use of metformin. The aim of this review article is to present a concise, comprehensive and critical overview of the aforementioned issue based on the analysis of available experimental research. Material and Methods. PubMed and Google Scholar databases were searched for relevant literature published in a fifteen-year period between 2008 and 2022. The following terms were used in the search: atypical antipsychotics, metformin, and weight gain. Only double-blind, placebo-controlled, randomized, and cohort studies were taken into consideration. Results. A total of 145 papers were analyzed, of which 10 papers with 852 subjects met the inclusion criteria. All the reviewed studies concluded that the adjunctive administration of metformin at a daily dose of 500 mg to 2,000 mg has significantly reduced atypical antipsychotic-induced weight gain, with a favorable effect on other metabolic parameters that were examined in the analyzed papers. Conclusion. Taking into account the increased cardiovascular morbidity and the consequent mortality among those who have been using atypical antipsychotics in the long term, it is necessary to assess the risks and benefits of introducing adjunctive metformin in every patient who is at risk of developing metabolic syndrome. In order to recommend the routine use of metformin in such indications, studies that would include a larger sample and a longer period of treatment are needed.

Review: Influence of the CYP450 Genetic Variation on the Treatment of Psychotic Disorders.

Second-generation antipsychotic metabolism is mainly carried out by the CYP450 superfamily, which is highly polymorphic. Therefore, knowing the influence of the different known CYP450 polymorphisms on antipsychotic plasmatic levels and, consequently, the biological effect could contribute to a deeper knowledge of interindividual antipsychotic treatment variability, prompting possible solutions. Considering this, this state of the art review aimed to summarize the current knowledge about the influence of the diverse characterized phenotypes on the metabolism of the most used second-generation antipsychotics. Forty studies describing different single nucleotide polymorphisms (SNPs) associated with the genes CYP1A2, CYP2D6, CYP3A4, CYP3A5, and ABCB1 and their influence on pharmacokinetics of olanzapine, clozapine, aripiprazole, risperidone, and quetiapine. Most of the authors concluded that although significant differences in the pharmacokinetic parameters between the different phenotypes could be observed, more thorough studies describing pharmacokinetic interactions and environmental conditions, among other variables, are needed to fully comprehend these pharmacogenetic interactions.

Is change over time in psychotic symptoms related to social functioning?

In psychosis, treatment often focuses on symptom reduction whereas social functioning is also essential. In this study, we investigate positive psychotic symptoms and medication use in relation to social functioning over a 3-year time-period in 531 patients diagnosed with psychosis. Furthermore, relations of positive symptoms with needs for care and quality of life were also investigated. Using repeated measures analysis, changes were measured over time. Hereafter, mixed model analyses were performed to determine the associations of social functioning, needs for care, and quality of life with psychotic symptoms and patient characteristics. Finally, we assessed differences in symptoms and medication dose between those with an increase and those with a decrease in social functioning. Patients significantly improved in social functioning, while psychotic symptoms increased. Improvement in social functioning was associated with younger age, higher IQ, and lower social functioning at T1, but not with positive symptoms. Also, improvement in social functioning was found to be related to a decrease in the dose of clozapine. Improvement in social functioning occurs despite worsening of positive symptoms. The findings suggest the need to further explore the relation between symptomatology, social functioning, and medication use. In the treatment of psychotic disorders, one should reconsider the strong focus on reducing psychotic symptoms. The current focus needs to shift much more toward improving functional outcome, especially when the patient expresses a desire for change in this respect.