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Pharmaceuticals
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Recent Advances in Psychopharmacology
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Recent Advances in Psychopharmacology

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 25 December 2024 | Viewed by 5115

Special Issue Editors

Prof. Dr. Roos Van Westrhenen

E-Mail Website1 Website2
Guest Editor
1. Parnassia Psychiatric Institute, Amsterdam, The Netherlands
2. Institute of Psychiatry, Psychology and Neuroscience (IoPPN) Kings College, London, UK
3. Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
4. St. John’s National Academy of Health Sciences, Bangalore, India
Interests: psychiatry; (psycho)pharmacology; pharmacogenetics; pharmacogenomics; genetics; pharmacokinetics; pharmacodynamics; pharmacovigilance; drug interactions; phenoconversion
Prof. Dr. Allan H. Young

grade E-Mail Website
Guest Editor
1. Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
2. South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Monks Orchard Road, Beckenham, Kent BR3 3BX, UK
Interests: psychopharmacology; bipolar disorder; major depressive disorder; novel treatments; cognition

Special Issue Information

Dear Colleagues,

Performing clinical trials in psychiatry is a challenge as it is difficult to include a sufficient number of patients and assess reliable outcome parameters, and due to the fact that drug companies as Astra Zeneca, Pfizer, Glaxo Smith Kline and Eli Lilly have stopped almost all psychopharmaca discoveries [1]. Nevertheless, in a recent overview of all the recent and current phase 2 or phase 3 clinical trials, n=43 were described for schizophrenia medication, n=11 for bipolar disorder, n=56 for major depressive disorder, n=29 for anxiety disorder and trauma related disorders, and n=17 for medication for treatment of substance disorders [2]. One has to bear in mind that, in general, the availability of new psychopharmaca to patients takes nearly nine years, and the likelihood of drug approval in psychiatry is only 6.2%. Thus, novel strategies in psychiatry are urgently needed [3].

We would like to add enhancing medication prescription with pharmacogenetics as another strategy. In general, only one-third of the patients respond to treatment with available medication in psychiatry [4,5]. Today, medication selection in psychiatry relies on a trial-and-error approach based mainly on physicians’ experience [4,5]. Pharmacogenetic testing can help in this process by determining the person-specific genetic factors that may predict clinical response and side effects associated with genetic variants that impact drug-metabolizing enzymes, drug transporters or drug targets [4–8].

In this Special Issue, some exciting examples of newly registered medications in psychiatry will be described, in addition to recent pharmacogenetic advances including the start of a clinical trial implementing pharmacogenetics in people with mood, anxiety, and psychotic disorders.

  1. Howes OD, Baxter L. The drug treatment deadlock in psychiatry and the route forward. World Psychiatry 2023;22(1): 2-4
  2. Correll, M. Solmi, S. Cortese, M. Fava, M. Højlund, HC. Kraemer, RS. McIntyre, DS. Pine, LS. Schneider, JM. Kane- The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de-risk trial programmes of novel agents, World Psychiatry 2023;22(1): 48-74
  3. Yatham LM All levels of the translational spectrum must be targeted to advance psychopharmacology and improve patient outcomes, World Psychiatry 2023;22(1): 75-76
  4. van Westrhenen& M. Ingelman-Sundberg. Editorial: From Trial and Error to Individualised Pharmacogenomics-Based Pharmacotherapy in Psychiatry. Frontiers in Pharmacology, 2021, doi: 10.3389/fphar.2021.725565
  5. Dutch Pharmacogenetics Working Group (DPWG) Guideline for the Gene-Drug Interaction between CYP2D6, CYP3A4 and CYP1A2 and Antipsychotics, L. Beunk, M Nijenhuis, B Soree,  de Boer-Veger, AM Buunk, H J Guchelaar, EJF Houwink, A Risselada, GAPJM. Rongen, RHN van Schaik, JJ Swen, D Touw, R van Westrhenen, VHM Deneer, J van der Weide Eur J Hum Gen 2023, https://doi.org/10.1038/s41431-023-01347-3
  6. Dutch Pharmacogenetics Working Group (DPWG) Guideline for the Gene-Drug Interaction between CYP2C19 and CYP2D6 and SSRIs" M. Nijenhuis, J. Brouwer, B. Soree, HJ. Guchelaar, J. Swen, R. van Schaik, J. van der Weide, G. Rongen, AM. Buunk, N. de Boer-Veger, E. Houwink, van Westrhenen, B. Wilffert, V. Deneer, and Hans Mulder. Eur J of Human Gen nov 2021, /doi.org/10.1038/s41431-021-01004-7
  7. Brown e.a. Pharmacogenomic Testing and Depressive Symptom Remission: A Systematic Review and Meta-Analysis of Prospective, Controlled Clinical Trials, Clin Pharm&Ther 2022; 112(6): 1303-1317
  8. Swen J, e.a. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet 2023;400(10374): 347-356

Prof. Dr. Roos Van Westrhenen
Prof. Dr. Allan H. Young
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • psychopharmaca
  • pharmacogenomics
  • pharmacogenetics
  • psychedelics
  • dementia drugs

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Published Papers (2 papers)

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17 pages, 1665 KiB  
Article
The Effects of CYP2C19 Genotype on Proxies of SSRI Antidepressant Response in the UK Biobank
by Win Lee Edwin Wong, Chiara Fabbri, Benjamin Laplace, Danyang Li, Roos van Westrhenen, Cathryn M. Lewis, Gavin Stewart Dawe and Allan H. Young
Pharmaceuticals 2023, 16(9), 1277; https://doi.org/10.3390/ph16091277 - 11 Sep 2023
Cited by 5 | Viewed by 3022
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used psychopharmaceutical treatment for major depressive disorder (MDD), but individual responses to SSRIs vary greatly. CYP2C19 is a key enzyme involved in the metabolism of several drugs, including SSRIs. Variations in the CYP2C19 gene [...] Read more.
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used psychopharmaceutical treatment for major depressive disorder (MDD), but individual responses to SSRIs vary greatly. CYP2C19 is a key enzyme involved in the metabolism of several drugs, including SSRIs. Variations in the CYP2C19 gene are associated with differential metabolic activity, and thus differential SSRI exposure; accordingly, the CYP2C19 genotype may affect the therapeutic response and clinical outcomes, though existing evidence of this link is not entirely consistent. Therefore, we analysed data from the UK Biobank, a large, deeply phenotyped prospective study, to investigate the effects of CYP2C19 metaboliser phenotypes on several clinical outcomes derived from primary care records, including multiple measures of antidepressant switching, discontinuation, duration, and side effects. In this dataset, 24,729 individuals were prescribed citalopram, 3012 individuals were prescribed escitalopram, and 12,544 individuals were prescribed sertraline. Consistent with pharmacological expectations, CYP2C19 poor metabolisers on escitalopram were more likely to switch antidepressants, have side effects following first prescription, and be on escitalopram for a shorter duration compared to normal metabolisers. CYP2C19 poor and intermediate metabolisers on citalopram also exhibited increased odds of discontinuation and shorter durations relative to normal metabolisers. Generally, no associations were found between metabolic phenotypes and proxies of response to sertraline. Sensitivity analyses in a depression subgroup and metabolic activity scores corroborated results from the primary analysis. In summary, our findings suggest that CYP2C19 genotypes, and thus metabolic phenotypes, may have utility in determining clinical responses to SSRIs, particularly escitalopram and citalopram, though further investigation of such a relationship is warranted. Full article
(This article belongs to the Special Issue Recent Advances in Psychopharmacology)
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25 pages, 2147 KiB  
Systematic Review
CYP2C19 Genetic Variants and Major Depressive Disorder: A Systematic Review
by Larissa Sousa Silva Bonasser, Calliandra Maria de Souza Silva, Caroline Ferreira Fratelli, Bruna Rodrigues Gontijo, Juliana Moura Alves Seixas, Livia Cristina Lira de Sá Barreto and Izabel Cristina Rodrigues da Silva
Pharmaceuticals 2024, 17(11), 1461; https://doi.org/10.3390/ph17111461 - 31 Oct 2024
Viewed by 736
Abstract
Major depressive disorder (MDD) affects over 300 million people globally and has a multifactorial etiology. The CYP2C19 enzyme, involved in metabolizing certain antidepressants, can influence treatment response. Following the PRISMA protocol and PECOS strategy, this systematic review assessed the variation in common CYP2C19 [...] Read more.
Major depressive disorder (MDD) affects over 300 million people globally and has a multifactorial etiology. The CYP2C19 enzyme, involved in metabolizing certain antidepressants, can influence treatment response. Following the PRISMA protocol and PECOS strategy, this systematic review assessed the variation in common CYP2C19 gene variants’ frequencies across populations with MDD, evaluating their impact on clinical characteristics and treatment response. We comprehensively searched five databases, identifying 240 articles, of which only nine within the last decade met our inclusion criteria. Except for one study that achieved 74.28% of STROPS items, the rest met at least 75% of GRIPS and STROPS guidelines for quality and bias risk assessment. The CYP2C19’s *1 allele, the *1/*1 genotype, and the NM phenotype, considered as references, were generally more frequent. Other CYP2C19 polymorphism frequencies exhibit significant variability across different populations. Some studies associated variants with MDD development, a more extended history of depression, prolonged depressive episodes, and symptom severity, while others reported no such association. Some studies confirmed variants’ effects on escitalopram and citalopram metabolism but not that of other drugs, such as sertraline, venlafaxine, and bupropion. Treatment tolerability and symptom improvement also varied between studies. Despite some common findings, inconsistencies highlight the need for further research to clarify the role of these polymorphisms in MDD and optimize treatment strategies. Full article
(This article belongs to the Special Issue Recent Advances in Psychopharmacology)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Effect of CYP2D6, CYP1A2, and CYP3A4 Variation on Antipsychotic Treatment Response
Lauren Varney, Elvira Bramon et al.

Demystifying the Antidepressant Mechanism of Action of Stinels, a Novel Class of Neuroplastogens: Positive Allosteric Modulators of the NMDA Receptor
John E. Donello et al.

Enchanting the Mind: Exploring the Logic and Conducting a Comprehensive Evaluation of AdipoRon’s Impact on Alzheimer’s Disease—A Systematic Review
Lucas Fornari Laurindo et al.

NMDA receptors and depression: linking psychopharmacology, pathology and physiology in a unifying hypothesis for the epigenetic code of neural plasticity
Stefano Comai et al.

 

 

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