OBJECTIVE: The \"early intervention\" paradigm in psychiatry holds significant promise for preventing psychosis. Recent evidence showed that individuals at clinical high risk for psychosis (CHR-P) with antipsychotic (AP) prescription at baseline have higher psychosis transition rates compared with those without AP, although the underlying cause remains unclear. In this article, we reviewed international guidelines on early intervention in CHR-P people, paying specific attention to clinical recommendations on AP treatment. Then, we comment on these suggestions in the light of recent empirical evidence examining AP prescription in CHR-P populations within \"real-world\" clinical settings.
METHODS: This search was conducted on PubMed/MEDLINE, PsycINFO, EMBASE, and Google, looking for both \"Guidelines AND CHR-P OR UHR OR Early Psychosis.\"
RESULTS: International guidelines generally recommend not using AP as first-line treatment, but only when psychosocial interventions have failed. CHR-P people with AP drug showed high prevalence rates and had more severe clinical picture at entry. Is this a \"warning signal\" for potentially higher psychosis transition risk? Is it a direct AP iatrogenic effect? Is it possible to detect specific CHR-P subgroup that may benefit from AP? These are the questions that this article seeks to explore.
CONCLUSIONS: The current framework for identifying CHR-P subjects has defined psychometric criteria mainly based on positive symptoms. In our opinion, this is reductive, especially for evaluating therapeutic outcomes and prognosis. A more comprehensive assessment considering quality of life, psychiatric comorbidity, persistent negative symptoms, subjective experience of CHR-P psychopathology, and social/personal recovery is thus needed.

This report presents challenging psychopharmacotherapy management of a psychotic disorder in a patient with a delicate pharmacogenetic profile and drug-drug interactions. A 31-year old woman diagnosed with schizophrenia in 2017 was referred by her psychiatrist to a clinical pharmacologist for interpretation of a pharmacogenetic test and advice regarding optimal psychopharmacotherapy. In spite of adherence to aripiprazole, olanzapine, risperidone, and levomepromazine, and rational anxiolytic therapy, she still experienced anxiety, anhedonia, loss of appetite, sleeping problems, and auditory hallucinations with commands to harm herself. Due to a lack of alternative therapeutic steps, low aripiprazole serum concentrations, and a lack of explanation for pharmacotherapy unresponsiveness, pharmacogenetic testing was performed. The patient was defined as CYP2D6 *1/*1, CYP1A2 *1F/*1F, CYP3A4 *1/*1B, CYP3A5 *1/*3, and having increased activity of the enzymes UGT1A4 and UGT2B7, intermediate activity of ABCB1 transporter, and low activity of COMT. Carbamazepine was discontinued, aripiprazole was increased to a maximum of 30 mg/day orally with long-acting injection (400 mg monthly), and olanzapine was increased to a daily dose of 35 mg orally. These changes led to an optimal therapeutic drug concentration and improved clinical status. At the last follow-up, the patient was without severe auditory hallucinations, became more engaged in daily life, had more interaction with others, had found a job, and even had started an emotional relationship. In psychiatry, pharmacogenetic testing is an important tool for guiding pharmacological therapy, particularly in patients with an unsatisfactory clinical response and a lack of alternative therapeutic steps for pharmacotherapy unresponsiveness.

Background and Objectives: Vertical rhythmic dyskinetic movements that are primarily drug-induced and affect solely the jaw, mouth, and lips without involving the tongue have been historically described as \"rabbit\" syndrome (RS). Evidence on the unique features and implications of this disorder remains limited. This literature review aims to evaluate the clinical-epidemiological profile, pathological mechanisms, and management of this movement disorder. Materials and Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction published between 1972 and 2024. Results: A total of 85 articles containing 146 cases of RS were found. The mean frequency of RS among adults in psychiatric hospitals was 1.2% (range 0-4.4%). The mean age of affected patients was 49.2 (SD: 17.5), and 63.6% were females. Schizophrenia was the most frequent comorbidity found in 47.6%, followed by bipolar disorder (17.8%), major depressive disorder (10.3%), and obsessive-compulsive disorder (3.7%). Five cases were idiopathic. The most common medications associated with RS were haloperidol (17%), risperidone (14%), aripiprazole (7%), trifluoperazine (5%), and sulpiride (5%). The mean duration of pharmacotherapy before RS was 21.4 weeks (SD: 20.6). RS occurred in association with drug-induced parkinsonism (DIP) in 27.4% and with tardive dyskinesia (TD) in 8.2% of cases. Antipsychotic modification and/or anticholinergic drugs resulted in full or partial recovery in nearly all reported cases in which they were prescribed. Conclusions: RS occurs as a distinct drug-induced syndrome associated primarily but not exclusively with antipsychotics. Distinguishing RS from TD is important because the treatment options for the two disorders are quite different. By contrast, RS may be part of a spectrum of symptoms of DIP with similar course, treatment outcomes, and pathophysiology.

To assess the effect of Long-acting injectable (LAI) antipsychotics in acutely ill patients, we systematically searched major databases for randomized controlled trials (RCTs) comparing LAIs with other LAIs, oral antipsychotics, or placebo in acutely symptomatic adults with schizophrenia-spectrum disorders. Data were analyzed with a random-effects network meta-analysis. Co-primary outcomes were efficacy (mean change in psychopathology rating scales) and acceptability (all-cause discontinuations) at study endpoint. Of 25 RCTs, 19 studies tested second-generation LAIs (SGA-LAIs) and six first-generation LAIs (FGA-LAIs). Due to a disconnected network, FGA-LAIs were analyzed separately, with poor data quality. The SGA-LAIs network included 8,418 individuals (males=63%, mean age=39.3 years). All SGA-LAIs outperformed placebo in reducing acute symptoms at study endpoint (median follow-up=13 weeks). They were more acceptable than placebo with the only exception of olanzapine, for which no differences with placebo emerged. Additionally, we distinguished between different LAI formulations of the same antipsychotic to explore potential pharmacokinetic differences. Most formulations outperformed placebo in the very short-term (2 weeks or less), regardless of the need for initial oral supplementation. SGA-LAIs are evidence-based treatments in acutely ill individuals with schizophrenia-spectrum disorders. Findings support the use of SGA-LAIs to manage psychopathology and improve adherence right from the acute phases of illness.

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Premature mortality in people living with a severe mental illness (SMI) is often attributed to multiple factors including the use of medicines such as antipsychotics. Second-generation antipsychotics (SGAs) are known to cause metabolic syndrome which can increase the risk of cardiovascular disease. Practice guidelines have recommended regular physical health monitoring, particularly of metabolic parameters, however, metabolic monitoring for people living with SMI using antipsychotics remains suboptimal. Therefore, highlighting the need for ongoing research. This scoping review aimed to provide an overview of current metabolic monitoring practices. We anticipate that this information will assist clinicians and policymakers and inform future research. The following databases were searched: MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), the Cochrane Database of Systemic Reviews (Wiley), APA PsycInfo (Ovid) and Scopus (Elsevier Science Publishers). The target group was adults (aged ≥ 18) diagnosed with SMI (including bipolar disorder, major depressive disorder and psychotic disorders) and taking SGAs. In total, 44 studies from 14 countries were retrieved. Our findings highlighted that most studies conducted in hospitals did not report on metabolic monitoring practices. Additionally, the roles and responsibilities of healthcare professionals in metabolic monitoring for SMI were infrequently described and parameters such as waist circumference and BMI were often poorly monitored. The scoping review highlights that no streamlined approach towards metabolic monitoring currently exists. There is a need to stipulate and define the roles and responsibilities of all health professionals involved in metabolic monitoring in SMI to optimise care for these individuals. Moreover, there is a need for ongoing research, particularly in the community setting, to promote increased accessibility to metabolic monitoring for SMI.

BACKGROUND: Many articles suggest that clozapine was strongly associated with a higher incidence of new-onset diabetes mellitus, and the issue has remained unsettled. Many articles have compared clozapine with FGAs, but few have compared clozapine with SGAs. We aimed to compare the risk of new-onset diabetes mellitus in adults with schizophrenia treated with clozapine and other SGAs.
METHODS: We conducted a comprehensive search of databases from their inception up until August 26, 2023. The specific databases include PubMed, Embase and others. We included non-randomized controlled trials involving the use of SGAs such as clozapine, olanzapine, risperidone, quetiapine, amisulpride, and zotepine, with a focus on new-onset diabetes mellitus as an outcome. We utilized odds ratio with 95 % credible intervals (95 % CI) as our effect size measures. The study protocol is registered with PROSPERO, number CRD42024511280.
RESULTS: We included 7 studies with sufficient data to include in the meta-analysis. A total of eight studies with 641,48 participants met the eligibility criteria. The OR of the incidence rates of new-onset diabetes between clozapine and olanzapine was 0.95 (95 % CI:[0.82-1.09]), between clozapine and risperidone was 1.25 (95 % CI: [1.09-1.44]), between clozapine and quetiapine was 1.44 (95 % CI: [0.92-2.25]).
CONCLUSIONS: In patients with schizophrenia, clozapine has been found to have a higher rate of new-onset diabetes mellitus compared to risperidone. However, there was no significant difference in incidence rate between clozapine versus olanzapine and quetiapine. These findings can assist clinicians in balancing the risks and benefits of those drugs.

Dementia is a disease most prevalent in the older adult population. The cognitive symptoms of dementia include impairments in problem-solving, memory, and language. Some patients experience noncognitive symptoms in addition to the cognitive symptoms of dementia. These noncognitive symptoms are called behavioral and psychological symptoms of dementia or BPSD. The primary objective of our study was to examine the therapeutic options, guidelines, and clinical considerations for the management of BPSD. The existing literature about BPSD was reviewed with searches in PubMed, MEDLINE, and online search platforms. Dysregulation of neurotransmission involving acetylcholine, dopamine, and serotonin has been shown to cause behavioral and psychological symptoms of Alzheimer\'s disease. BPSD can include hallucinations, agitation, delusions, anxiety, apathy, abnormal body movements, irritability, depression, disinhibition, and sleep or appetite changes. Pharmacologic therapies used in the treatment of BPSD include antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Treatment can be tailored to the specific noncognitive symptoms that are experienced. The use of these agents may be limited based on recommendations from the Beers Criteria®, STOPP criteria, treatment guidelines, and FDA warnings.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are highly prevalent in people living with dementia. Second-generation antipsychotics (SGAs) are commonly used to treat BPSD, but their comparative efficacy and acceptability are unknown.
METHODS: The standard mean difference (SMD) was used to pool the fixed effects of continuous outcomes. We calculated ORs with corresponding 95% credible intervals (CI) for the categorical variable. Efficacy was defined as the scores improved on the standardised scales. Acceptability was defined as the all-cause dropout rate. Tolerability was defined as the discontinuation rate due to adverse effects (AEs). The relative treatment rankings were reported with the surface under the cumulative curve. The AE outcomes included mortality, cerebrovascular adverse events (CVAEs), falls, sedation, extrapyramidal symptoms and urinary symptoms.
RESULTS: Twenty randomised controlled trials with a total of 6374 individuals containing 5 types of SGAs (quetiapine, olanzapine, risperidone, brexpiprazole and aripiprazole) with intervention lengths ranging from 6 weeks to 36 weeks were included in this network meta-analysis. For the efficacy outcome, compared with the placebo, brexpiprazole (SMD=-1.77, 95% CI -2.80 to -0.74) was more efficacious, and brexpiprazole was better than quetiapine, olanzapine and aripiprazole. Regarding acceptability, only aripiprazole (OR=0.72, 95% CI 0.54 to 0.96) was better than the placebo, and aripiprazole was also better than brexpiprazole (OR=0.61, 95% CI 0.37 to 0.99). In terms of tolerability, olanzapine was worse than placebo (OR=6.02, 95% CI 2.87 to 12.66), risperidone (OR=3.67, 95% CI 1.66 to 8.11) and quetiapine (OR=3.71, 95% CI 1.46 to 9.42), while aripiprazole was better than olanzapine (OR=0.25, 95% CI 0.08 to 0.78). Quetiapine presented good safety in CVAE. Brexpiprazole has better safety in terms of falls and showed related safety in sedation among included SGAs.
CONCLUSIONS: Brexpiprazole showing great efficacy in the treatment of BPSD, with aripiprazole showing the highest acceptability and olanzapine showing the worst tolerability. The results of this study may be used to guide decision-making.

Schizophrenia presents a complex mental health challenge, often inadequately addressed by existing antipsychotic treatments, leading to persistent symptoms and adverse effects. Hence, developing alternative therapeutic approaches is crucial. Cannabidiol (CBD), a nonpsychoactive compound in Cannabis sativa, has been extensively explored for its therapeutic potential in treating psychiatric disorders, including schizophrenia. CBD exhibits antipsychotic, anxiolytic, and neuroprotective effects. However, distinguishing the individual effects of CBD and THC remains challenging. Therefore, this review aims to critically analyze the potential role of CBD as an adjunctive therapy in schizophrenia treatment. The therapeutic action of CBD may involve activating the 5-hydroxytryptamine 1A receptors and suppressing the G-protein-coupled receptor 55, thereby affecting various neurotransmitter systems. Additionally, the anti-inflammatory and antioxidative effects of CBD may contribute to alleviating neuroinflammation linked to schizophrenia. Compared to typical antipsychotics, CBD demonstrates a lower incidence of side effects and it exhibited favorable tolerability in clinical trials. A 2012 clinical trial demonstrated the efficacy of CBD in reducing both positive and negative symptoms of schizophrenia, presenting a safer profile than that of traditional antipsychotics. However, further research is needed to fully establish the safety and efficacy of CBD as an adjunctive treatment. Future research directions encompass exploring detailed antipsychotic mechanisms, long-term safety profiles, interactions with current antipsychotics, optimal dosing, and patient-specific factors such as genetic predispositions. Despite these research needs, the potential of CBD to enhance the quality of life and symptom management positions it as a promising candidate for innovative schizophrenia treatment approaches.