Is Therapeutic Drug Monitoring Relevant for Antidepressant Drug Therapy? Implications From a Systematic Review and Meta-Analysis With Focus on Moderating Factors

Funk, Cleo S. M.; Hart, X.M.; Gründer, Gerhard; Hiemke, Christoph; Elsner, Björn; Kreutz, Reinhold; Riemer, Thomas

doi:10.3389/fpsyt.2022.826138

Cited by 14 publications

(6 citation statements)

References 45 publications

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“…In lower concentration ranges, there seems to be a positive direction of effect, increasing efficacy with increasing concentrations. In contrast, in higher concentration ranges, a negative direction could be observed, indicating a decline in efficacy with increasing concentrations ( 12 ). However, we did not find any data on the upper cut-off value of CIT concentrations in this study, although the recommended therapeutic reference range of CIT is 50–110 ng/mL by AGNP ( 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…As the associations between concentration and clinical effects of antidepressants have become a wide clinical concern, some reviews have been published earlier. One systematic review published in 2022 ( 12 ) focused on the association between the concentration and clinical effect of antidepressants, which were divided into several categories such as SSRI, tricyclic antidepressants (TCA), tetracyclic antidepressants (Tetra-CA), and selective serotonin-noradrenaline reuptake-inhibitors (SSNRI), but did not provide detailed information on CIT or escitalopram to guide clinical practice. From the perspective of review findings, both the previous review and our present review reported that research on the association between the concentration and clinical effect of antidepressants has yielded ambiguous results.…”

Section: Discussionmentioning

confidence: 99%

“…The search strategy was confirmed by an experienced information library specialist. The reference lists of previous guidelines, expert consensus, reviews ( 4 , 6 – 8 , 12 ) and included literature were searched for relevant studies.…”

Section: Methodsmentioning

confidence: 99%

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Toward therapeutic drug monitoring of citalopram in depression? Insights from a systematic review

Song

Jiang

et al. 2023

Front. Psychiatry

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BackgroundWithin the framework of individualized psychopharmacotherapy, therapeutic drug monitoring (TDM) has gained increasing relevance. In the absence of high-quality evidence, the TDM of citalopram (CIT) and the recommended therapeutic ranges of the plasma concentrations have been proposed by guidelines. However, the correlation between the plasma concentration of CIT and treatment outcomes has not been well established. Therefore, the aim of this systematic review was to evaluate the relationship between plasma CIT concentration and treatment outcomes in depression.Research design and methodsPubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese databases (CNKI, Wanfang Data and Sinomed) were searched up to August 6, 2022. We included clinical studies evaluating the correlation between the plasma CIT concentration and treatment outcomes in patients with depression receiving CIT treatment. Outcomes measured included efficacy, safety, medication adherence, and cost-related outcomes. A narrative synthesis was performed to summarize findings from individual studies. This study was performed according to the Preferred Reporting Items for Systematic Reviews, Meta-Analysis (PRISMA) and the reporting guideline for Synthesis without meta-analysis (SWiM).ResultsEleven studies involving 538 patients were included in total. The reported outcomes were mainly efficacy (n = 11) and safety (n = 3); one study reported the duration of hospitalization, and no study reported medication adherence. Regarding the efficacy outcomes, three studies revealed the plasma CIT concentration-response relationship and proposed a lower limit of 50 or 53 ng/mL, whereas this was not found in the rest of the studies. Regarding adverse drug events (ADEs), one study reported more ADEs in the low-concentration group (<50 ng/mL vs. >50 ng/mL), which is not convincing from the perspective of pharmacokinetics/pharmacodynamics. Regarding the cost-related outcomes, only one study reported that the high CIT concentration group (≥50 ng/mL) contributed to shortening the hospitalization duration, but it did not provide detailed information, including direct medical expenses and multiple potential factors contributing to longer hospital stays.ConclusionsA definite correlation between plasma concentration and clinical or cost-related outcomes of CIT cannot be drawn, whereas a tendency toward improved efficacy in patients with plasma concentration above 50 or 53 ng/mL was suggestive from limited evidence.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Toward therapeutic drug monitoring of citalopram in depression? Insights from a systematic review

Song

Jiang

et al. 2023

Front. Psychiatry

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“…Dose-response meta-analyses report conflicting results, but, in general, do not support high dose ranges for SSRIs 10 11 . Meta-analyses that consider drug exposure, i. e., blood concentration, were not able to find a clear drug exposure – response relationship for SSRIs yet 12 . For escitalopram, only one prospective cohort study investigating such a relationship has been reported.…”

Section: Introductionmentioning

confidence: 99%

Low Escitalopram Concentrations in Patients with Depression predict Treatment Failure: A Naturalistic Retrospective Study

Hart

Amann

Brand³

et al. 2023

Pharmacopsychiatry

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Introduction Cross sectional therapeutic drug monitoring (TDM) data mining introduces new opportunities for the investigation of medication treatment effects to find optimal therapeutic windows. Medication discontinuation has been proven useful as an objective surrogate marker to assess treatment failure. This study aimed to investigate the treatment effects of escitalopram and pharmacokinetic influences on blood levels using retrospectively assessed data from a TDM database. Methods Data was collected from 134 patients longitudinally treated with escitalopram for whom TDM was requested to guide drug therapy. Escitalopram metabolism was estimated by the log-transformed dose-corrected concentrations and compared within subpopulations differing in age, gender, renal function, smoking status, body mass index, and comedication. Results Patients with a depressive episode who were treated with escitalopram and discontinued the treatment within the hospital stay showed lower serum concentrations compared to patients who continued escitalopram treatment with a concentration of 15 ng/mL separating both groups. Variability was high between individuals and factors influencing blood levels, including dose, sex, and age. Comedication that inhibits cytochrome P450 (CYP) 2C19 isoenzymes were further found to influence escitalopram pharmacokinetics independent of dose, age or sex. Discussion Medication switch is a valuable objective surrogate marker to assess treatment effects under real-world conditions. Of note, treatment discontinuation is not always a cause of insufficient response but may also be related to other factors such as medication side effects. TDM might not only be useful in addressing these issues but titrating drug concentrations into the currently recommended reference range for escitalopram will also increase response in non-responders and avoid treatment failure in underdosed patients.

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“…Monoamine oxidase inhibitors (MAOIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and atypical antidepressants, are the five main categories of antidepressants specifically utilized in psychopharmacotherapy [ 4 ]. Sertraline (SSRIs), duloxetine (SNRIs), mirtazapine (atypical antidepressant), and escitalopram (SSRIs), constituted the largest percentage (96.36%) of antidepressant prescriptions.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Antidepressants Utilization for Patients Visiting Psychiatric Out-Patient Clinic in a Tertiary Care Hospital

et al. 2022

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Depression is a prevalent mental health condition treated with antidepressants and other psychotropic medications. This study aimed to assess the utilization pattern of antidepressants among patients visiting the outpatient clinic of the psychiatry department of a tertiary care hospital. The study included the patients who visited the study site and fulfilled the mental and behavioral diagnostic criteria for depression. The demographic and clinical details, including drugs prescribed, were documented in a study-specific data collection form. The ratio of Prescribed Daily Dose to Defined Daily Dose (PDD: DDD) was calculated to assess the adequacy of antidepressant utilization. Data total of 154 patients were collected. A total of 22 psychotropic drugs were used among the study patients as mono (n = 70), dual (n = 69), triple (n = 10), or quadruple therapy (n = 1). Escitalopram was the most often prescribed antidepressant out of the nine antidepressants alone and in combination and was used in slightly high doses (PDD: DDD ratio 1.6). Sertraline, paroxetine, and desvenlafaxine, were used in adequate doses (PDD: DDD between 1 and 1.1), and fluoxetine, duloxetine, amitriptyline, imipramine, and mirtazapine, were used in inadequate doses (PDD: DDD <0.5). Our study findings reveal the need for continuous assessment of antidepressants medications usage in a hospital set up.

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Is Therapeutic Drug Monitoring Relevant for Antidepressant Drug Therapy? Implications From a Systematic Review and Meta-Analysis With Focus on Moderating Factors

Cited by 14 publications

References 45 publications

Toward therapeutic drug monitoring of citalopram in depression? Insights from a systematic review

Toward therapeutic drug monitoring of citalopram in depression? Insights from a systematic review

Low Escitalopram Concentrations in Patients with Depression predict Treatment Failure: A Naturalistic Retrospective Study

Analysis of Antidepressants Utilization for Patients Visiting Psychiatric Out-Patient Clinic in a Tertiary Care Hospital

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