Recent Advances in Psychopharmacology

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

Deadline for manuscript submissions: 30 April 2024 | Viewed by 2062

Special Issue Editors

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
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

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Keywords

  • psychopharmaca
  • pharmacogenomics
  • pharmacogenetics
  • psychedelics
  • dementia drugs

Published Papers (1 paper)

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Research

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 3 | Viewed by 1659
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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