Pregabalin augmentation of antidepressants in major depression - results from a European multicenter study

Dold, Markus; Bartova, Lucie; Fugger, Gernot; Mitschek, Marleen M M; Fabbri, Chiara; Serretti, Alessandro; Mendlewicz, Julien; Souery, Daniel; Zohar, Joseph; Montgomery, Stuart; Kasper, Siegfried

doi:10.1016/j.jad.2021.09.063

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…Genome wide association signals for depression also showed enrichment for the targets of antidepressants, suggesting that they may also help to reveal other effective treatment targets and more effective interventions. Pregabalin (Dobrea et al, 2012; Karaiskos et al, 2013; Generoso et al, 2017; Dold et al, 2022) and Modafinil (Goss et al, 2013) are both supported by sparse non-randomized evidence supporting their efficacy in depression and related conditions. Our findings provide further proof of principle, that GWAS is a useful means of identifying therapeutically relevant drug targets and treatments.…”

Section: Discussionmentioning

confidence: 99%

“…Pregabalin is an effective treatment for neuropathic pain, focal seizures and generalized anxiety disorder (GAD) (Generoso et al, 2017). Studies have shown that it is effective for the treatment of GAD-related depressive symptoms (Dold et al, 2022), but randomized controlled trial (RCT) evidence supporting its use in MD is weak. While pregabalin is sometimes prescribed to augment other effective treatments in medication-resistant MD (Dold et al ., 2022), there is now justification to consider its efficacy in MD within the context of an RCT.…”

Section: Discussionmentioning

confidence: 99%

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Genome-wide study of half a million individuals with major depression identifies 697 independent associations, infers causal neuronal subtypes and biological targets for novel pharmacotherapies

McIntosh,

Lewis

2024

Preprint

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In a genome-wide association study (GWAS) meta-analysis of 685,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries and across diverse and admixed ancestries, we identify 697 independent associations at 636 loci, 293 of which are novel. Using fine-mapping and functional genomic tools, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. Leveraging new single-cell gene expression data, we conducted a causal neural cell type enrichment analysis that implicates dysregulation of excitatory and inhibitory midbrain and forebrain neurons, peptidergic neurons, and medium spiny neurons in MD. Our findings are enriched for the targets of antidepressants and provide potential antidepressant repurposing opportunities (e.g., pregabalin and modafinil). Polygenic scores (PGS) trained using either European or multi-ancestry data significantly predicted MD status across all five diverse ancestries and explained a maximum of 5.8% of the variance in liability to MD in Europeans. These findings represent a major advance in our understanding of MD across global populations. MD GWAS reveals known and novel biological targets that may be used to target and develop pharmacotherapies addressing the considerable unmet need for effective treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genome-wide study of half a million individuals with major depression identifies 697 independent associations, infers causal neuronal subtypes and biological targets for novel pharmacotherapies

McIntosh,

Lewis

2024

Preprint

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“…Genome-wide genotyping was performed with Infinium PsychArray-24 BeadChip. Additional information on this study is available elsewhere (Fanelli et al, 2021(Fanelli et al, , 2022bDold et al, 2022).…”

Section: European Group For the Study Of Resistant Depressionmentioning

confidence: 99%

Polygenic scores of subcortical brain volumes as possible modulators of treatment response in depression

Oliva,

Martone,

Fanelli

et al. 2023

Preprint

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A significant proportion of patients with major depressive disorder (MDD) do not experience remission after one or more pharmacological treatments. Research has explored brain structural measures, particularly the hippocampus, as potential predictors of treatment response in MDD, as well as genetic factors.This study investigated the association of polygenic scores (PGSs) for seven subcortical brain volumes (including the hippocampus, nucleus accumbens, amygdala, and caudate nucleus) with treatment non-response and non-remission in MDD.Patients with MDD were recruited in the context of five clinical studies, including a total of 3,637 individuals. PGSs were estimated using a Bayesian framework and continuous shrinkage priors (PRS-CS-auto) after standard genotype quality control and imputation. Logistic regressions were performed between PGSs and non-response or non-remission in each sample, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, using a random-effect model.Caudate volume PGS was nominally associated with non-remission (OR=1.09, 95% CI=1.01–1.19, p=0.036). Leave-one-out sensitivity analyses suggested a possible association with the amygdala and thalamus PGSs. However, no association was significant after multiple testing correction.These results, although preliminary, suggest a possible link between caudate volume PGS and lack of symptom remission. Methodological improvements in PGSs estimation and statistical power may enhance their predictive performance and provide a contribution to precision psychiatry.

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“…Так, результати великого рандомізованого плацебо-конт рольованого дослідження демонструють, що додавання прегабаліну до антидепресантів є кращим, ніж продовження лікування ними [21]. Тому прегабалін із успіхом застосовують у лі- [22]. Дози прегабаліну, що застосовувалися в дослідженнях у пацієнтів з депресією, були в межах рекомендованого терапевтичного діапазону (75-600 мг/добу) [23,24].…”

Section: чи впливає вибір антидепресанту на ефективність лікування?unclassified

Поєднання Тривоги Та Депресії: Чому Іноді Лікування Не Допомагає?

2023

UMJ

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Редакція журналу «Український медичний часопис» Значна неоднорідність відповіді на лікування є основною проблемою лікування депресії та тривожних розладів. Незважаючи на те що наявні методи лікування є безпечними, як лікарям, так і пацієнтам доводиться мати справу зі значною варіабельністю результатів: 20-30% хворих не реагують на застосування 2 або більше антидепресантів [1]. Задачу вибору полегшують масштабні мережеві метааналізи та розуміння тонких механізмів фармакологічної дії. Так, серед інших антидепресантів есциталопрам вирізняється швидкістю настання ефекту, вищою або порівнянною ефективністю та переносимістю. При тривалому прийомі есциталопрам продемонстрував профілактичну дію щодо рецидивів. До того ж він має низький потенціал взаємодії з іншими ліками. Ці та інші властивості зумовлюють широке застосування есциталопраму у пацієнтів різних вікових груп, включаючи дітей та підлітків, з різними основними та супутніми патологіями, включаючи ішемічну хворобу серця, інсульт та хворобу Альцгеймера.

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Pregabalin augmentation of antidepressants in major depression - results from a European multicenter study

Cited by 5 publications

References 33 publications

Genome-wide study of half a million individuals with major depression identifies 697 independent associations, infers causal neuronal subtypes and biological targets for novel pharmacotherapies

Genome-wide study of half a million individuals with major depression identifies 697 independent associations, infers causal neuronal subtypes and biological targets for novel pharmacotherapies

Polygenic scores of subcortical brain volumes as possible modulators of treatment response in depression

Поєднання Тривоги Та Депресії: Чому Іноді Лікування Не Допомагає?

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