The Role of Pharmacogenetics in Personalizing the Antidepressant and Anxiolytic Therapy

Radosavljević, Milica; Štrac, Dubravka Švob; Jančić, Jasna; Samardžić, Janko

doi:10.3390/genes14051095

Cited by 13 publications

(5 citation statements)

References 206 publications

(289 reference statements)

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“…Somatic drugs can also affect plasma concentrations of psychotropic drugs via CYP interactions if these are relevant substrates ( 20 ). CYP interactions are partly also genetically determined, which makes them a focus of interest for personalised medicine ( 21 ). Therefore, even if the potential for CYP interaction exists theoretically, not all interactions will be of clinical relevance in all patients.…”

Section: Discussionmentioning

confidence: 99%

Serious adverse drug events associated with psychotropic treatment of bipolar or schizoaffective disorder: a 17-year follow-up on the LiSIE retrospective cohort study

Truedson,

Ott,

Wahlström

et al. 2024

Front. Psychiatry

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IntroductionMood stabilisers and other psychotropic drugs can lead to serious adverse drug events (ADEs). However, the incidence remains unknown. We aimed to (a) determine the incidence of serious ADEs in patients with bipolar or schizoaffective disorders, (b) explore the role of lithium exposure, and (c) describe the aetiology.MethodsThis study is part of the LiSIE (Lithium—Study into Effects and Side Effects) retrospective cohort study. Between 2001 and 2017, patients in the Swedish region of Norrbotten, with a diagnosis of bipolar or schizoaffective disorder, were screened for serious ADEs to psychotropic drugs, having resulted in critical, post-anaesthesia, or intensive care. We determined the incidence rate of serious ADEs/1,000 person-years (PY).ResultsIn 1,521 patients, we identified 41 serious ADEs, yielding an incidence rate of 1.9 events per 1,000 PY. The incidence rate ratio (IRR) between ADEs with lithium present and causally implicated and ADEs without lithium exposure was significant at 2.59 (95% CI 1.20–5.51; p = 0.0094). The IRR of ADEs in patients <65 and ≥65 years was significant at 3.36 (95% CI 1.63–6.63; p = 0.0007). The most common ADEs were chronic lithium intoxication, oversedation, and cardiac/blood pressure-related events.DiscussionSerious ADEs related to treatment of bipolar (BD) or schizoaffective disorder (SZD) were uncommon but not rare. Older individuals were particularly at risk. The risk was higher in individuals exposed to lithium. Serum lithium concentration should always be checked when patients present with new or unclear somatic symptoms. However, severe ADEs also occurred with other mood stabilisers and other psychotropic drugs.

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Section: Discussionmentioning

confidence: 99%

Serious adverse drug events associated with psychotropic treatment of bipolar or schizoaffective disorder: a 17-year follow-up on the LiSIE retrospective cohort study

Truedson,

Ott,

Wahlström

et al. 2024

Front. Psychiatry

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“…Pharmacotherapy for neuropsychiatric disorders, such as anxiety and depression, has been characterized by significant interindividual variability in drug response and the development of side effects. Pharmacogenetic research on depression and anxiety has focused on genetic polymorphisms affecting metabolism via cytochrome P450 (CYP) 54 . In antidepressant drug treatment, most drugs are metabolized via the polymorphic cytochrome P450 enzyme CYP2D6 55 .…”

Section: Discussionmentioning

confidence: 99%

Systems biology approaches to identify potential targets and inhibitors of the intestinal microbiota to treat depression

Teng

Gao

et al. 2023

Sci Rep

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Depression is a common mental disease, with some patients exhibiting ideas and behaviors such as self-harm and suicide. The drugs currently used to treat depression have not achieved good results. It has been reported that metabolites produced by intestinal microbiota affect the development of depression. In this study, core targets and core compounds were screened by specific algorithms in the database, and three-dimensional structures of these compounds and proteins were simulated by molecular docking and molecular dynamics software to further study the influence of intestinal microbiota metabolites on the pathogenesis of depression. By analyzing the RMSD gyration radius and RMSF, it was finally determined that NR1H4 had the best binding effect with genistein. Finally, according to Lipinski's five rules, equol, genistein, quercetin and glycocholic acid were identified as effective drugs for the treatment of depression. In conclusion, the intestinal microbiota can affect the development of depression through the metabolites equol, genistein and quercetin, which act on the critical targets of DPP4, CYP3A4, EP300, MGAM and NR1H4.

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“…Recent studies have emphasized the importance of interactions between genetic factors and exposure to stressors in promoting psychiatric disorders ( Radosavljevic et al, 2023 ). In psychiatry, stress, which can induce epigenetic changes, is believed to be a major environmental factor in disease variability.…”

Section: Insights From Stress-induced Models Of Depression In Rodentsmentioning

confidence: 99%

Of Mice and Men: The Inter-individual Variability of the Brain's Response to Drugs

Löscher

2024

eNeuro

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Biological variation is ubiquitous in nature. Despite highly standardized breeding and husbandry under controlled environmental conditions, phenotypic diversity exists in laboratory mice and rats just as it does in humans. The resulting inter-individual variability affects various characteristics of animal disease models, including the responsiveness to drugs. Thus, the common practice of averaging data within an experimental group can lead to misinterpretations in neuroscience and other research fields. In this commentary, the impact of inter-individual variation in drug responsiveness is illustrated by examples from the testing of antiseizure medications in rodent temporal lobe epilepsy models. Individual mice and rats rendered epileptic by treatment according to standardized protocols fall into groups that either do or do not respond to antiseizure medications, thus mimicking the clinical situation in patients with epilepsy. Population responses are not normally distributed, and divergent responding is concealed in averages subjected to parametric statistical tests. Genetic, epigenetic, and environmental factors are believed to contribute to inter-individual variation in drug response but the specific molecular and physiological causes are not well understood. Being aware of inter-individual variability in rodents allows an improved interpretation of both behavioral phenotypes and drug effects in a pharmacological experiment.

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The Role of Pharmacogenetics in Personalizing the Antidepressant and Anxiolytic Therapy

Cited by 13 publications

References 206 publications

Serious adverse drug events associated with psychotropic treatment of bipolar or schizoaffective disorder: a 17-year follow-up on the LiSIE retrospective cohort study

Serious adverse drug events associated with psychotropic treatment of bipolar or schizoaffective disorder: a 17-year follow-up on the LiSIE retrospective cohort study

Systems biology approaches to identify potential targets and inhibitors of the intestinal microbiota to treat depression

Of Mice and Men: The Inter-individual Variability of the Brain's Response to Drugs

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