Advancements in Antipsychotics

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 3373

Special Issue Editor


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Guest Editor
Department of Pharmacy Practice, Wayne State University, Detroit, MI 48201, USA
Interests: antipsychotics; pharmacoepigenomics; pharmacometabolomics; pharmacoproteomics; insulin resistance; metabolic disease

Special Issue Information

Dear Colleagues,

Antipsychotic medications are the primary pharmacotherapeutic option used in the treatment of severe mental illness, including schizophrenia and bipolar disorder; however, their use is expanding to several other populations and disease states. Antipsychotics, while efficacious, exhibit a high degree of interindividual effectiveness as well as side effects leading to non-adherence. The exact mechanisms underlying the heterogeneous response to antipsychotic treatment remain to be fully elucidated. The aim of this Special Issue is to collect and publish findings on recent advancements in antipsychotic research. This Special Issue is especially focused on omic-type studies of antipsychotic treatment outcomes but can also include imaging studies, other mechanism-type studies or adjunct treatment studies. Submissions can include original research or review articles.

Dr. Kyle Burghardt
Guest Editor

Manuscript Submission Information

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Keywords

  • antipsychotics
  • mechanisms
  • omic
  • efficacy
  • side effects
  • pathways
  • clinical
  • pre-clinical

Published Papers (3 papers)

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13 pages, 970 KiB  
Article
Long-Acting Injectable Second-Generation Antipsychotics in Seriously Ill Patients with Schizophrenia: Doses, Plasma Levels, and Treatment Outcomes
by Juan José Fernández-Miranda, Silvia Díaz-Fernández, Francisco Javier Cepeda-Piorno and Francisco López-Muñoz
Biomedicines 2024, 12(1), 165; https://doi.org/10.3390/biomedicines12010165 - 12 Jan 2024
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Abstract
This research studies the dose–plasma level (PL) relationship of second-generation antipsychotics, together with the treatment outcomes achieved, in seriously ill people with schizophrenia. An observational, prospective, one-year follow-up study was carried out with patients (N = 68) with severe schizophrenia treated with paliperidone [...] Read more.
This research studies the dose–plasma level (PL) relationship of second-generation antipsychotics, together with the treatment outcomes achieved, in seriously ill people with schizophrenia. An observational, prospective, one-year follow-up study was carried out with patients (N = 68) with severe schizophrenia treated with paliperidone three-month (PP3M) or aripiprazole one-month (ARIM). Participants were divided into standard-dose or high-dose groups. PLs were divided into “standard PL” and “high PL” (above the therapeutic reference range, TRR) groups. The dose/PL relationship, and severity, hospitalizations, tolerability, compliance, and their relationship with doses and PLs were evaluated. There was no clear linear relationship between ARIM or PP3M doses and the PLs achieved. In half of the subjects, standard doses reached PLs above the TRR. The improvements in clinical outcomes (decrease in clinical severity and relapses) were related to high PLs, without worse treatment tolerability or adherence. All participants remained in the study, regardless of dose or PL. Clinical severity and hospitalizations decreased significantly more in those patients with high PLs. Considering the non-linear dose–PL relationship of ARIM and PP3M in people with severe schizophrenia, PLs above the TRR are linked to better treatment outcomes, without worse tolerability. The need in a notable number of cases for high doses to reach those effective PLs is highlighted. Full article
(This article belongs to the Special Issue Advancements in Antipsychotics)
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21 pages, 4935 KiB  
Article
Extrapyramidal Side Effects with Chronic Atypical Antipsychotic Can Be Predicted by Labeling Pattern of FosB and phosphoThr34-DARPP-32 in Nucleus Accumbens
by Sonia G. Prieto, Maria Camila Almeida, João C. S. Silva, Elaine Del-Bel and Marcela B. Echeverry
Biomedicines 2023, 11(10), 2677; https://doi.org/10.3390/biomedicines11102677 - 29 Sep 2023
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Abstract
Extrapyramidal side effects (EPS) can be induced by neuroleptics that regulate the expression of transcription factor FosB and dopaminergic mediator DARPP-32 in the striatum. However, the long-term neurobiological changes in striatal projection neurons resulting from a cumulative dosage of typical and atypical antipsychotics [...] Read more.
Extrapyramidal side effects (EPS) can be induced by neuroleptics that regulate the expression of transcription factor FosB and dopaminergic mediator DARPP-32 in the striatum. However, the long-term neurobiological changes in striatal projection neurons resulting from a cumulative dosage of typical and atypical antipsychotics are poorly understood. The present study aimed to determine the differential and long-lasting changes in FosB distribution and DARPP-32 phosphorylation in the striatum and nucleus accumbens (NAc) associated with chronic antipsychotic-induced EPS. Male C57Bl/6J mice received daily injections of Olanzapine (Olz, 15 mg/kg), Clozapine (Clz, 20 mg/kg), or Haloperidol (Hal, 1 mg/kg), for a period of 11 weeks with a 4-day withdrawal period before the last dosage. Catalepsy for detection of EPS, along with open-field and rotarod tests, were assessed as behavioral correlates of motor responses. Additionally, FosB and phosphorylated-DARPP-32 immunohistochemistry were examined in striatal regions after treatment. All antipsychotics produced catalepsy and reduced open-field exploration, such as impaired rota-rod performance after Olz and Hal. The washout period was critical for Clz-induced side effects reduction. Both Olz and Clz increased FosB in NAc Shell-region, and phosphoThr34-DARPP-32 in NAc. Only Clz reduced phosphoThr75-DARPP-32 in the dorsal striatum and showed FosB/phosphoThr34-Darpp-32-ir in the NAc Core region. This study provides evidence that atypical antipsychotics such as Olz and Clz also give rise to EPS effects frequently associated with a cumulative dosage of typical neuroleptics such as Hal. Nevertheless, FosB/phosphoThr34-Darpp-32-ir in the NAc Core region is associated with hypokinetic movements inhibition. Full article
(This article belongs to the Special Issue Advancements in Antipsychotics)
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16 pages, 1279 KiB  
Systematic Review
Metabolomics, Lipidomics, and Antipsychotics: A Systematic Review
by Kyle J. Burghardt, Megan Kajy, Kristen M. Ward and Paul R. Burghardt
Biomedicines 2023, 11(12), 3295; https://doi.org/10.3390/biomedicines11123295 - 13 Dec 2023
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Abstract
Antipsychotics are an important pharmacotherapy option for the treatment of many mental illnesses. Unfortunately, selecting antipsychotics is often a trial-and-error process due to a lack of understanding as to which medications an individual patient will find most effective and best tolerated. Metabolomics, or [...] Read more.
Antipsychotics are an important pharmacotherapy option for the treatment of many mental illnesses. Unfortunately, selecting antipsychotics is often a trial-and-error process due to a lack of understanding as to which medications an individual patient will find most effective and best tolerated. Metabolomics, or the study of small molecules in a biosample, is an increasingly used omics platform that has the potential to identify biomarkers for medication efficacy and toxicity. This systematic review was conducted to identify metabolites and metabolomic pathways associated with antipsychotic use in humans. Ultimately, 42 studies were identified for inclusion in this review, with all but three studies being performed in blood sources such as plasma or serum. A total of 14 metabolite classes and 12 lipid classes were assessed across studies. Although the studies were highly heterogeneous in approach and mixed in their findings, increases in phosphatidylcholines, decreases in carboxylic acids, and decreases in acylcarnitines were most consistently noted as perturbed in patients exposed to antipsychotics. Furthermore, for the targeted metabolomic and lipidomic studies, seven metabolites and three lipid species had findings that were replicated. The most consistent finding for targeted studies was an identification of a decrease in aspartate with antipsychotic treatment. Studies varied in depth of detail provided for their study participants and in study design. For example, in some cases, there was a lack of detail on specific antipsychotics used or concomitant medications, and the depth of detail on sample handling and analysis varied widely. The conclusions here demonstrate that there is a large foundation of metabolomic work with antipsychotics that requires more complete reporting so that an objective synthesis such as a meta-analysis can take place. This will then allow for validation and clinical application of the most robust findings to move the field forward. Future studies should be carefully controlled to take advantage of the sensitivity of metabolomics while limiting potential confounders that may result from participant heterogeneity and varied analysis approaches. Full article
(This article belongs to the Special Issue Advancements in Antipsychotics)
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