lithium response Dotaz Zobrazit nápovědu
- MeSH
- biomedicínský výzkum MeSH
- lidé MeSH
- lithium aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
Mezi faktory, které mohou ovlivňovat účinky léčiv, patří současné podávání jiných farmak. Způsobů, kterými spolu léky mohou vzájemně interagovat je několik, ale nejčastěji se lékové interakce dělí na farmakokinetické (absorpce, distribuce, metabolizmus, exkrece), farmakodynamické nebo na smíšené. Znalost mechanizmů, kterými nějaká interakce probíhá je důležitá v praxi, neboť při znalosti mechanizmu interakce můžeme ovlivnit její průběh nebo se jí někdy zcela záměrně můžeme vyhnout. Některé důležité interakce mezi léčivy se odehrávají na úrovni dvou či více mechanizmů. Tabulka lékových interakcí antidepresiv a lithia je rozdělena do následujících částí: nejprve jsou uvedeny interagující léčiva, výsledek lékové interakce a její mechanizmus, klinická závažnost a dokumentace vážící se k dané interakci. Jestliže hodnotíme nějakou potenciální lékovou interakci zaměřujeme se na její klinický význam a závažnost. Potenciálně závažná léková interakce je zvláště důležitá z hlediska hodnocení risku a benefitu terapeutických možností. Při vhodné úpravě dávkování nebo úpravě režimu, můžeme řadě negativních účinků většiny interakcí předejít. V tabulce jsou uvedeny 4 stupně závažnosti interakcí, označené písmeny A-D. Úroveň dokumentace je označena čísly 1-4.
One of the factors that can alter the response to drug is the concurrent administration of other drugs. There are several mechanisms by which drugs may interact, but most can be categorized as pharmacokinetic (absorption, distribution, metabolism, excretion), pharmacodnamic or combined interaction. Knowledge of the mechanism by which a given drug interaction occurs is often clinically useful, since the mechanism may influence both the time course and the methods of circumventing the interaction. Some important drug interactions occur as a result of two or more mechanisms. The table of antidepressant and lithium drug interaction of antidepressant drugs and lithuim listed below is divided into the following sections: interacting drugs, outcome and mechanism of the interaction, clinical relevance and documentation of the interaction. When evaluating any potential drug ineraction, a primary concern is the clinical relevance or significance of the interaction. The potential severity of the interaction is particularly important in assessing the risk vs benefit of therapeutic alternatives. With appropriate dosage adjustments or modification of the administration schedule, the negative effects of most interactions can be avoided. In the table there are four degree of relevance of interaction and they are defined by letters A-D. Documentation levels are marked of numbers 1-4.
Jak je lithium používáno v ČR, jaké mají psychiatři praktické zkušenosti s lithiem a názory na jeho používání, se pokusil zjistit dotazník, který byl distribuován na neuropsychofarmakologické konferenci.
The purpose of the questionnaire distributed on the neuropsychopharmacologic conference was to establish the situation of lithium use in the Czech Republic, such as psychiatrist‘s experiences with lithium and their views about it.
Psychiatrický výzkum je limitován řadou faktorů, mezi nimiž podstatnou roli hraje diagnóza. Validita psychiatrických diagnóz je zpochybnéna jednak tím, že neznáme patofyziologii duševních nemocí, jednak absencí diagnostických testů. Robins a Guze (1970) navrhli pět kritérií k validizaci psychiatrických diagnostických kategorií. V tomto přehledu shrnuji data, která ukazují, že bipolární porucha s kompletní odpovědí na léčbu lithiem splňuje kriteria Robinse a Guzeho. Tito pacienti 1) mají specifický klinický obraz, 2) liší se od respondérů na jiné typy dlouhodobé léčby; 3) odpověď na lithium je dlouhodobě stabilní, 4) má charakteristický genetický profil a 5) koreluje s určitými biologickými markery. Vzhledem k těmto vlastnostem jsou lithioví respondéři vhodnou populací pro výzkum etiologických faktorů u poruch nálady.
Accurate diagnosis is prominent among the factors limiting psychiatric research. Validity of psychiatric diagnosis is problematic in light of unknown pathophysiology and non-existent diagnostic tests. Robins and Guze (1970) proposed five criteria that should aid in defining a valid psychiatric diagnosis. In this paper I show that bipolar disorder responsive to lithium meets the Robins and Guze criteria by being 1) clinically distinct, 2) different from the forms of bipolar disorder responsive to other long term treatments, 3) longitudinally stable, 4) familial, and 5) likely associated with specific biological markers. These properties make bipolar disorder responsive to lithium particularly promising in search for etiological factors in mood disorders.
- MeSH
- bipolární porucha diagnóza genetika klasifikace MeSH
- farmakogenetika metody MeSH
- genetická predispozice k nemoci klasifikace prevence a kontrola MeSH
- lidé MeSH
- lithium aplikace a dávkování farmakokinetika MeSH
- následné studie MeSH
- psychopatologie klasifikace MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
Telomeres consist of exanucleotide tandem repeats and proteins complexes at the end of chromosome ends. Telomeres shorten at each cell division, and as such telomere length is a marker of cellular age. Accelerated telomere shortening and cell senescence have been associated with a number of chronic medical conditions, including psychiatric disorders, where increased prevalence of age-related disorders and shorter telomere length have been reported. Shorter telomeres in psychiatric patients are thought to be the consequence of allostatic load, consisting in the overactivation of allostatic systems due to chronic exposure to severe medical conditions and failure to adapt to chronic stressful stimuli. Most of the studies on telomere length in psychiatry have focused on major depressive disorder, but recent findings have shown shorter leukocyte telomere length in bipolar disorder patients and suggested that lithium may counteract telomeres shortening. These findings provided new insights into the pathophysiology of bipolar disorder and the mechanism of action of lithium. In this review we will present findings from the literature on telomere length in bipolar disorder, with a specific focus on lithium. We will also discuss advances and limitations of published work as well as methodological issues and potential confounding factors that should be taken into account when designing research protocols to study telomere length.
- MeSH
- bipolární porucha krev diagnóza farmakoterapie MeSH
- homeostáza telomer účinky léků fyziologie MeSH
- lidé MeSH
- lithium farmakologie terapeutické užití MeSH
- telomery účinky léků fyziologie MeSH
- výsledek terapie MeSH
- zkracování telomer účinky léků fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Lithium is regarded as a first-line treatment for bipolar disorder (BD), but partial response and non-response commonly occurs. There exists a need to identify lithium non-responders prior to initiating treatment. The Pharmacogenomics of Bipolar Disorder (PGBD) Study was designed to identify predictors of lithium response. METHODS: The PGBD Study was an eleven site prospective trial of lithium treatment in bipolar I disorder. Subjects were stabilized on lithium monotherapy over 4 months and gradually discontinued from all other psychotropic medications. After ensuring a sustained clinical remission (defined by a score of ≤3 on the CGI for 4 weeks) had been achieved, subjects were followed for up to 2 years to monitor clinical response. Cox proportional hazard models were used to examine the relationship between clinical measures and time until failure to remit or relapse. RESULTS: A total of 345 individuals were enrolled into the study and included in the analysis. Of these, 101 subjects failed to remit or relapsed, 88 achieved remission and continued to study completion, and 156 were terminated from the study for other reasons. Significant clinical predictors of treatment failure (p < 0.05) included baseline anxiety symptoms, functional impairments, negative life events and lifetime clinical features such as a history of migraine, suicidal ideation/attempts, and mixed episodes, as well as a chronic course of illness. CONCLUSIONS: In this PGBD Study of lithium response, several clinical features were found to be associated with failure to respond to lithium. Future validation is needed to confirm these clinical predictors of treatment failure and their use clinically to distinguish who will do well on lithium before starting pharmacotherapy.
- MeSH
- bipolární porucha * diagnóza farmakoterapie genetika MeSH
- farmakogenetika MeSH
- lidé MeSH
- lithium terapeutické užití MeSH
- prospektivní studie MeSH
- sloučeniny lithia terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
OBJECTIVES: The Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale) is the most widely used clinical measure of lithium response phenotypes. We assess its performance against recommended psychometric and clinimetric standards. METHODS: We used data from the Consortium for Lithium Genetics and a French study of lithium response phenotypes (combined sample >2500) to assess reproducibility, responsiveness, validity, and interpretability of the A scale (assessing change in illness activity), the B scale, and its items (assessing confounders of response) and the previously established response categories derived from the Total Score for the Alda scale. RESULTS: The key findings are that the B scale is vulnerable to error measurement. For example, some items contribute little to overall performance of the Alda scale (eg, B2) and that the B scale does not reliably assess a single construct (uncertainty in response). Machine learning models indicate that it may be more useful to employ an algorithm for combining the ratings of individual B items in a sequence that clarifies the noise to signal ratio instead of using a composite score. CONCLUSIONS: This study highlights three important topics. First, empirical approaches can help determine which aspects of the performance of any scale can be improved. Second, the B scale of the Alda is best applied as a multidimensional index (identifying several independent confounders of the assessment of response). Third, an integrated science approach to precision psychiatry is vital, otherwise phenotypic misclassifications will undermine the reliability and validity of findings from genetics and biomarker studies.
Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.
- MeSH
- bipolární porucha * farmakoterapie genetika MeSH
- celogenomová asociační studie MeSH
- deprese MeSH
- depresivní porucha unipolární * farmakoterapie genetika MeSH
- lidé MeSH
- lithium terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org ). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.
- MeSH
- bipolární porucha * farmakoterapie genetika MeSH
- deprese MeSH
- depresivní porucha unipolární * farmakoterapie genetika MeSH
- genetická predispozice k nemoci MeSH
- lidé MeSH
- lithium terapeutické užití MeSH
- multifaktoriální dědičnost MeSH
- rizikové faktory MeSH
- schizofrenie * farmakoterapie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
