Atypical antipsychotic Lumateperone Beyond Schizophrenia: Seeking clarity in a time of Uncertainty

Lumateperone (ITI-007) is a serotonin 5HT2A tosylate salt with high affinity for dopamine D2 and D1 receptors and the serotonin transporter. It is unusual in that it controls serotonin, dopamine, and glutamate neurotransmission concurrently, all of which have been implicated in severe mental illness. Consider it a multi-targeted ligand and multifunctional modulator of the serotoninergic system with possible precognitive, antipsychotic, antidepressant, and anxiolytic properties. While lumateperone has been explored as a new agent for schizophrenia therapy, it also provides a unique therapeutic option for a range of other psychiatric and neurological diseases, including behavioural signs of dementia or Alzheimer's disease, sleep problems, and bipolar depression. Additionally, it had a better safety profile than placebo, with no significant extrapyramidal side effects, hyperprolactinemia, or changes in cardiometabolic or endocrine characteristics. Additional study is needed to validate and analyse lumateperone's effectiveness, as well as to identify prospective therapeutic targets. This article gives a comprehensive overview of the most notable results and potential future applications of this chemical in personalised medicine, particularly for neurodegenerative diseases.

Understanding the Effects of Antipsychotics on Appetite Control

Antipsychotic drugs (APDs) represent a cornerstone in the treatment of schizophrenia and other psychoses. The effectiveness of the first generation (typical) APDs are hampered by so-called extrapyramidal side effects, and they have gradually been replaced by second (atypical) and third-generation APDs, with less extrapyramidal side effects and, in some cases, improved efficacy. However, the use of many of the current APDs has been limited due to their propensity to stimulate appetite, weight gain, and increased risk for developing type 2 diabetes and cardiovascular disease in this patient group. The mechanisms behind the appetite-stimulating effects of the various APDs are not fully elucidated, partly because their diverse receptor binding profiles may affect different downstream pathways. It is critical to identify the molecular mechanisms underlying drug-induced hyperphagia, both because this may lead to the development of new APDs, with lower appetite-stimulating effects but also because such insight may provide new knowledge about appetite regulation in general. Hence, in this review, we discuss the receptor binding profile of various APDs in relation to the potential mechanisms by which they affect appetite.

Cigarette Smoking and Schizophrenia: Etiology, Clinical, Pharmacological, and Treatment Implications

Recent data suggests that the prevalence of smoking in schizophrenia remains high. While reports suggest that smoking increases the risk of developing schizophrenia, the potential causative role of smoking in this relationship needs further investigation. Smokers with schizophrenia are more likely to have more intense positive symptoms and lower cognitive function, but diminished intensity of extrapyramidal side effects than nonsmoking patients with schizophrenia. They were also more likely to exhibit aggressive behaviour compared to nonsmokers, which could suggest higher levels of baseline aggression. The significant cost associated with regular tobacco expenditure can detract from investment in key domains. Large-scale trials have shown that pharmacotherapy for smoking cessation is effective and does not worsen the risk of developing neuropsychiatric symptoms compared to placebo. Electronic cigarette use among schizophrenia patients is high, and there is emerging evidence supportive of its efficacy. Future improvements include large-scale trials assessing the utility, efficacy, and safety of electronic cigarettes in schizophrenia patients.

Erratum: Extrapyramidal side effects in first-episode schizophrenia treated with flupenthixol decanoate

No abstract available.

MTHFD1 1958 G>A Genetic Polymorphism (rs2236225) Dichotomy in Schizophrenia: Lower Manifestation Risks, but More Severe Negative Symptoms

Despite a large amount of data on the association of folate metabolism disturbances with different aspects of schizophrenia, the role of the MTHFD1 1958 G>A polymorphism in this disorder is barely studied. The aim of this study was to assess the distribution of alleles and genotypes frequencies of MTHFD1 1958 G>A in patients with schizophrenia and healthy controls and to study the association of allele/genotype carriage of this SNP with biochemical markers of one-carbon metabolism and with the severity of schizophrenia symptoms. Methods: In 57 patients with schizophrenia and 37 healthy volunteers the carriage of alleles/genotypes of the MTHFD1 1958 G>A and biochemical markers of folate metabolism disturbances were evaluated. Clinical symptoms of schizophrenia and the severity of extrapyramidal side effects of therapy were assessed in patients. Results: an association of the wild GG genotype with schizophrenia was shown (GG versus AG / AA: χ2 = 7.31; p = 0.007). The serum folate level in carriers of the wild genotype GG is lower (in all participants p = 0.024, in patients p = 0.10), and the level of cobalamin in this subgroup is higher (in all participants p = 0.047, in patients p = 0.091) than in carriers of other genotypes. Patients carrying the G allele had less severe negative symptoms (p = 0.0041) and extrapyramidal side effects of antipsychotics (p = 0.054), than patients with AA genotype. The age of psychosis manifestation is the later, the more wild alleles G are present in the genotype (p = 0.00195).

Acute Extrapyramidal Side Effects from Smoked Haloperidol

Introduction. Haloperidol is a dopamine receptor antagonist used to treat patients with psychotic disorders. Especially at high doses, haloperidol carries a higher risk of extrapyramidal symptoms (EPS) compared to second-generation antipsychotics. Few cases of haloperidol misuse are found in the medical literature. Case Presentation. We describe a patient with schizophrenia who smoked marijuana mixed with crushed haloperidol tablets. After the smoking of cannabis and haloperidol, the patient presented to the emergency department (ED) with suicidal ideation, psychosis, and acute dystonia. With the administration of intramuscular diphenhydramine at the ED, the dystonia resolved in less than an hour. To our knowledge, this is the first report on haloperidol misuse by smoking. Conclusion. Clinicians should be aware that patients might misuse prescribed antipsychotics via unconventional routes, potentially combined with other substances.

Antipsychotic-induced extrapyramidal side effects: A systematic review and meta-analysis of observational studies

Background Antipsychotic agents are the basis for the pharmacological management of acute and chronic schizophrenia, bipolar disorders, mood disorders with psychotic feature, and other psychotic disorders. Antipsychotic medication use is frequently associated with unfavorable adverse effects such as extrapyramidal side effects (EPSEs). Hence, this systematic review and meta-analysis was aimed to determine the magnitude of antipsychotic-induced EPSEs. Method A literature search was conducted using legitimate databases, indexing services, and directories including PubMed/MEDLINE (Ovid®), EMBASE (Ovid®), google scholar and WorldCat to retrieve studies. Following screening and eligibility, the relevant data were extracted from the included studies using an Excel sheet and exported to STATA 15.0 software for analyses. The Random effects pooling model was used to analyze outcome measures at a 95% confidence interval. Besides, publication bias analysis was conducted. The protocol has been registered on PROSPERO with ID: CRD42020175168. Result In total, 15 original articles were included for the systematic review and meta-analysis. The pooled prevalence of antipsychotic-induced EPSEs among patient taking antipsychotic medications was 37% (95% CI: 18–55%, before sensitivity) and 31% (95% CI: 19–44%, after sensitivity). The prevalence of antipsychotic-induced parkinsonism, akathisia, and tardive dyskinesia was 20% (95% CI: 11–28%), 11% (95% CI: 6–17%), and 7% (95% CI: 4–9%), respectively. To confirm a small-study effect, Egger’s regression test accompanied by funnel plot asymmetry demonstrated that there was a sort of publication bias in studies reporting akathisia and tardive dyskinesia. Conclusion The prevalence of antipsychotic-induced EPSEs was considerably high. One in five and more than one in ten patients experienced parkinsonism and akathisia, respectively. Appropriate prevention and early management of these effects can enhance the net benefits of antipsychotics.