Influence of Concomitant Medications on the Total Clearance and the Risk for Supra-therapeutic Plasma Concentrations of Citalopram. A Population-Based Cohort Study

Wenzel-Seifert, Katharina; Brandl, R; Hiemke, Christoph; Haen, Ekkehard

doi:10.1055/s-0034-1390477

Cited by 7 publications

(3 citation statements)

References 20 publications

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“…When combining drugs that are inhibitors or inducers of drug metabolizing enzymes (▶Table 2, 3), pharmacokinetic drug-drug interactions may occur if the comedication is a substrate of the inhibited or induced enzyme. Many interactions have been found by TDM either by chance or retrospective analysis of TDM data bases [183,502,918,974,1054,1055,1295]. Among environmental factors, smoking is of high clinical relevance for drugs that are substrates of CYP1A2 [336,343].…”

Section: Absorption Distribution and Elimination Of Neuropsychiatricmentioning

confidence: 99%

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Bergemann²,

et al. 2017

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Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

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Section: Absorption Distribution and Elimination Of Neuropsychiatricmentioning

confidence: 99%

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Bergemann²,

et al. 2017

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“…The difference in the serum CITA concentrations of this study might be explained in part by the sampling time for citalopram, taking comedications and CYP2C19 polymorphisms. Because citalopram is extensively metabolized by CYP2C19 [ 18 ], CYP2C19 polymorphisms, and the use of CYP2C19 inhibitors, especially proton pump inhibitors could increase the citalopram concentrations [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Serum N-Desmethylcitalopram Concentrations are Associated with the Clinical Response to Citalopram of Patients with Major Depression

Özbey

Yücel²,

Bodur

et al. 2018

Psychiatry Investig

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Objective Citalopram (CITA) is a widely used and well-tolerated selective serotonin reuptake inhibitor. The aim of the study was to evaluate the possible influences of serum concentrations of CITA and its major metabolite n-desmethylcitalopram (NDCITA) on the efficacy and tolerability of CITA in patients with major depressive disorder. Methods The study included 46 outpatients with major depressive disorder who received CITA. The efficacy and tolerability were assessed for 6 weeks. Serum CITA and NDCITA levels were measured at the 4th week. Results The HDRS17 total scores of the patients with high NDCITA and CITA & NDCITA concentrations showed a more significant reduction compared to the patients with expected and low serum NDCITA and CITA & NDCITA concentrations. However, we did not observe a correlation between the serum concentrations and the side effects of CITA, NDCITA, and CITA & NDCITA. Conclusion Our results suggested the potential contribution of NDCITA to the antidepressant effect of CITA. Further studies involving larger clinical samples are required to confirm the impact of serum NDCITA concentrations on the efficacy of CITA.

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“…Most pharmacokinetic DDI of psychotropic drugs occur at the metabolic level involving the CYP enzyme system [15]. Psychotropic DDI give rise to highly variable serum-concentrations of the respective victim drug [9,10,16], leading to ADRs [17,18]. Thereby, elderly patients are particularly sensitive to ADRs, especially because of age-related changes in pharmacokinetics and pharmacodynamics [19,20], a higher prevalence of comorbidity [21] and a high rate of drug consumption [2] which increases the risk of drug interactions [3].…”

Section: Introductionmentioning

confidence: 99%

Prevalence and type of potential pharmacokinetic drug-drug interactions in old aged psychiatric patients

Hefner¹,

Unterecker²,

Ben-Omar³

et al. 2015

Contemp Behav Health Care

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Purpose: The number of prescribed drugs increases with age, and resulting polypharmacy bears the risk of drug-drug interactions (DDI). We assessed the prevalence and type of cytochrome P450 (CYP) associated pharmacokinetic DDI that were considered as clinically relevant in elderly psychiatric patients under conditions of every day pharmacotherapy.Methods: For retrospective analysis a large therapeutic drug monitoring (TDM) data base was used. Patients included were elderly in-and outpatients, aged ≥ 65 years with a psychiatric disorder for whom serum level measurements of a psychotropic drug had been requested. Medication data were examined for co-prescription of clinically relevant CYP inhibitors or inducers and drugs that are substrates of these enzymes (victim drugs).Results: Data from 1243 patients (65.3% female) with a mean (± standard deviation) age of 73 ± 6 years were available for analysis. Mean number of prescribed drugs was 5.3 ± 3.4 per patient. Moderate (n=189, 73.8%) or strong (n=67, 26.2%) CYP inhibitors or inducers were prescribed in 18.9% of all patients. Most frequently prescribed CYP inhibitors were duloxetine (CYP2D6 inhibitor, n=73, 31.7%), melperone (CYP2D6 inhibitor, n=63, 27.4%) and omeprazole (CYP2C19 inhibitor, n=20, 8.7%). Carbamazepine was the most commonly prescribed CYP inducer (primarily CYP3A4 inducer, n=25, 96.2%). Taken inhibitory, inducing and substrate properties of combined drugs together, CYP-mediated DDI considered as clinically relevant could be detected in 133 (10.7%) of included patients.Conclusions: CYP-mediated DDI are common among elderly psychiatric patients. To avoid potentially supra-or sub-therapeutic concentrations of victim drugs, physicians should be more aware of these preventable interactions and adjust the dose.

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Influence of Concomitant Medications on the Total Clearance and the Risk for Supra-therapeutic Plasma Concentrations of Citalopram. A Population-Based Cohort Study

Cited by 7 publications

References 20 publications

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Serum N-Desmethylcitalopram Concentrations are Associated with the Clinical Response to Citalopram of Patients with Major Depression

Prevalence and type of potential pharmacokinetic drug-drug interactions in old aged psychiatric patients

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