QTc Time Correlates with Amitriptyline and Venlafaxine Serum Levels in Elderly Psychiatric Inpatients

Hefner, Gudrun; Hahn, Martina; Hohner, M; Roll, Sybille C.; Klimke, A.; Hiemke, Christoph

doi:10.1055/s-0044-102009

Cited by 20 publications

(22 citation statements)

References 28 publications

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“…Anticholinergic side effects on the central nervous system (the cognitive disorder, confusion, hallucinations, delirium) and in the peripheral nervous system (dry mouth, dry eyes, constipation) (Rudolph, Salow, Angelini, & McGlinchey, 2008). Amitriptyline usage needs to be considered because of the high risk in geriatric medicine (Hefner, Hahn, Hohner, Roll, Klimke, & Hiemke, 2018).…”

Section: Discussionmentioning

confidence: 99%

Potentially Inappropriate Medication Use in Geriatric Based on 2015 Beers Criteria

Yuliawati

Krisdiawati²,

Sutrisno³

et al. 2020

SCIENTIA J. Far. Kes.

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Tujuan penelitian ini untuk menganalisis peresepan penggunaan obat pada pasien geriatri rawat jalan di rumah sakit "X" Kota Jambi periode Agustus 2016 sampai Agustus 2017. Penelitian ini dilakukan pada bulan Desember 2017 sampai dengan Maret 2018 menggunakan alat skrining kriteria eksplisit Beers 2015. Penelitian ini merupakan penelitian observasional dengan rancangan deskriptif data yang bersifat retrosfektif pada resep pasien geriatri rawat jalan di salah satu rumah sakit Kota Jambi. Berdasarkan asal poliklinik, pasien terbanyak berasal dari poli penyakit dalam (22 %). Penggunaan obat pada peresepan pasien geriatri rawat jalan di salah satu rumah sakit Kota Jambi sebanyak 239 resep (79.4 %) yang termasuk dalam Kriteria Beers 2015. Terdapat delapan resep yang mengandung lebih dari satu macam obat (3.4 %). Penggunaan obat pada peresepan pasien geriatri yang termasuk dalam Kriteria Beers 2015 cukup tinggi dengan prevalensi penggunaan obat paling banyak digunakan yaitu diazepam dan asam mefenamat. Obat yang digunakan pada pasien geriatri di RS X yang masuk Kriteria Beers 2015 adalah alprazolam, amitripthylin, asam mefenamat, klonazepam, diazepam, digoksin, ibuprofen, ketoprofen, ketorolak meloksicam, natrium diklofenak, ranitidin, spironolakton dan triheksifenidil.

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Section: Discussionmentioning

confidence: 99%

Potentially Inappropriate Medication Use in Geriatric Based on 2015 Beers Criteria

Yuliawati

Krisdiawati²,

Sutrisno³

et al. 2020

SCIENTIA J. Far. Kes.

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“…Even if previously no difference in frequencies of adverse drug reactions related to venlafaxine in patients with active moiety concentrations higher and lower than the alert level (800 ng/mL; Hiemke et al, 2018) was shown, there were reports of QTc prolongation during venlafaxine therapy (Bavle, 2015;Hefner et al, 2019;Jasiak and Bostwick, 2014;Schoretsanitis et al, 2019b;Wenzel-Seifert et al, 2011). However, these alterations seemed only to affect elderly patients (Hefner et al, 2019;Unterecker et al, 2015). Accordingly, in the present study QTc time was found to be below the upper limit of a normal QTc time (450 ms; Wenzel-Seifert et al, 2011) in all patients.…”

Section: Discussionmentioning

confidence: 97%

“…Since in everyday clinical settings active moiety concentrations above the therapeutic reference range were often reported (Hansen et al, 2017;Paulzen et al, 2015;Unterecker et al, 2012Unterecker et al, , 2015, it can be assumed that clinicians deliberately go beyond the therapeutic reference range in order to achieve a better drug effect. Even if previously no difference in frequencies of adverse drug reactions related to venlafaxine in patients with active moiety concentrations higher and lower than the alert level (800 ng/mL; Hiemke et al, 2018) was shown, there were reports of QTc prolongation during venlafaxine therapy (Bavle, 2015;Hefner et al, 2019;Jasiak and Bostwick, 2014;Schoretsanitis et al, 2019b;Wenzel-Seifert et al, 2011). However, these alterations seemed only to affect elderly patients (Hefner et al, 2019;Unterecker et al, 2015).…”

Section: Discussionmentioning

confidence: 97%

Higher venlafaxine serum concentrations necessary for clinical improvement? Time to re-evaluate the therapeutic reference range of venlafaxine

et al. 2020

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Background: The therapeutic reference range for venlafaxine in antidepressant treatment has been defined as 100 to 400 ng/mL. However, in an everyday setting active moiety concentrations above the therapeutic reference range were often reported. Aim: The aim of this study was to re-evaluate the therapeutic reference range of venlafaxine. Methods: In-patients (⩽60 years) with major depressive episodes receiving antidepressant monotherapy with venlafaxine during routine clinical treatment were included in this observational study. Depressive symptom severity was evaluated on a weekly basis using the Hamilton Depression Rating Scale (HAMD-21), and therapeutic drug monitoring analyses were performed. Resting electrocardiograms were analyzed in week 3, week 5 and week 7 of study participation. Results: Clinical improvement from baseline to week 4 was significantly associated with increasing serum concentrations of the active moiety of venlafaxine ( N = 23, Pearson correlation, p = 0.009), but not with the dose of venlafaxine. Patients achieving remission showed significantly higher serum concentrations than patients achieving response/non-response (Kruskal–Wallis test, p = 0.019). Moreover, in patients with serum concentrations above 400 ng/mL time to remission and time to response was significantly shorter than in patients with concentrations below 400 ng/mL (Mantel–COX test, p = 0.001; p = 0.010). QTc time was below the upper limit of a normal QTc time (450 ms) for all patients. Conclusion: The serum concentration of the active moiety and not the dose determined the effect of venlafaxine. Shorter remission times without ECG alterations in patients with serum concentrations above the therapeutic reference range suggest a re-evaluation of the therapeutic reference range for venlafaxine in larger studies.

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“…The dose reduction observed in the oldest patients could possibly be explained by the increased focus on adverse effects associated with higher doses of venlafaxine [ 32 ]. Recently, an association between QTc prolongation and high serum concentration was demonstrated for older people using venlafaxine [ 33 ]. Increased awareness about the age-related higher serum concentrations in older individuals treated with venlafaxine could be another explanation, but reductions in prescribed doses between 2007 and 2017 in individuals aged < 65 years were similar, indicating that age-related changes in pharmacokinetics and pharmacodynamics are not the reason for the observed dose reduction [ 19 – 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a higher risk may be justified if treatment response is improved. Nevertheless, there is increasing evidence on both the dose-dependent effect of antidepressants and between serum levels and clinical improvement/adverse effects, including no increased effect when the recommended reference ranges are exceeded [ 27 , 33 – 38 ]. A recent work from our laboratory demonstrated a u-shaped risk of switching from escitalopram to alternative antidepressant therapy that correlated with both high and low serum concentrations of escitalopram, which likely reflects unacceptable adverse effects or lack of effect, respectively [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Use of Antidepressants in Older People during a 10-Year Period: An Observational Study on Prescribed Doses and Serum Levels

et al. 2020

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Background According to previous studies, older patients frequently have serum concentrations of antidepressant medication above the recommended reference range. Objective The aim of this study was to investigate whether prescribed doses of antidepressants and the proportion of individuals with serum concentrations above the recommended reference range in older individuals (≥ 65 years) have changed over a 10-year period in Norway. Methods Serum concentration measurements and prescribed daily doses of antidepressants in 2007 and 2017 were extracted from a therapeutic drug monitoring (TDM) database at the Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway. The database contains routine follow-up serum concentration measurements of psychotropic drugs for patients from all parts of the country. For citalopram, escitalopram, sertraline, mirtazapine and venlafaxine, the differences between 2007 and 2017 in mean prescribed doses and the proportion of patients with at least one serum concentration above the reference range, according to the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) guidelines, were compared. For the proportion of patients with serum concentrations above the recommended reference range, differences between individuals aged 65-79 and ≥ 80 years were also examined. Results The analyses of prescribed doses included 806 patients from 2007 and 1932 patients from 2017, with 972 and 2441 TDM samples, respectively. Between 2007 and 2017, modest reductions in prescribed daily doses were observed for citalopram (20 vs. 17 mg/day) and escitalopram (11 vs. 10 mg/day), but the proportion of patients with serum concentrations above the recommended reference range was unchanged for both drugs, i.e. 11.5% vs. 12.4% for citalopram and 3.6% vs. 2.9% for escitalopram. For mirtazapine and venlafaxine, prescribed doses were reduced from 28 to 25 mg/day and 150 to 125 mg/day, respectively. A significant reduction in the proportion of individuals with serum concentrations above the recommended reference range was observed for mirtazapine (27.1% vs. 11.5%) and for individuals aged ≥ 80 years using venlafaxine (60.0% vs. 30.0%). For sertraline, no differences in prescribed doses or serum concentrations above the recommended reference range were observed. Conclusions Over a 10-year period, prescribed doses of antidepressants have been slightly reduced in older Norwegian patients, but a considerable proportion is still exposed to high serum concentrations of antidepressants.

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QTc Time Correlates with Amitriptyline and Venlafaxine Serum Levels in Elderly Psychiatric Inpatients

Cited by 20 publications

References 28 publications

Potentially Inappropriate Medication Use in Geriatric Based on 2015 Beers Criteria

Potentially Inappropriate Medication Use in Geriatric Based on 2015 Beers Criteria

Higher venlafaxine serum concentrations necessary for clinical improvement? Time to re-evaluate the therapeutic reference range of venlafaxine

Use of Antidepressants in Older People during a 10-Year Period: An Observational Study on Prescribed Doses and Serum Levels

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