Venlafaxine induced QTc interval prolongation in a therapeutic dose

Bavle, Amar

doi:10.1016/j.ajp.2015.06.001

Cited by 13 publications

(9 citation statements)

References 7 publications

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“…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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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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“…Patients with MetS are more likely to have a prolonged QTc interval, which increases the risk of cardiovascular mortality (Li et al, 2009). Additionally, venlafaxine may increase the duration of QTc interval in therapeutic doses, which could occur due to inhibition of the outward delayed rectifier potassium current (I Kr ) in ventricular myocytes (Lestas et al, 2005;Bavle, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…However, there is evidence that antidepressants, including venlafaxine, are independently associated with the worsening or even development of MetS, by an increase in systolic and diastolic blood pressure, as well as in LDL cholesterol levels and body weight (McIntyre et al, 2010). Moreover, venlafaxine itself may cause cardiac electrical disturbances, such as QT interval and QRS complex prolongation or lethal forms of dysrhythmias (Khalifa et al, 1999;Bavle, 2015;Vicen et al, 2016;Sasváriová et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

The effect of venlafaxine on blood pressure and ECG in rats fed with high-fat-fructose diet

Sasváriová

Michalikova

Kaprinay

et al. 2019

Interdisciplinary Toxicology

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Metabolic syndrome represents one of the major health, social and economic issues nowadays, and affects more than 25% people worldwide. Being a multifactorial health problem, metabolic syndrome clusters various features, such as obesity, dyslipidemia, hyperglycemia and hypertension. Each of these disturbances represents a risk factor for developing cardiovascular disease. Moreover, patients with metabolic syndrome are more likely to suffer from depression, thus treatment with antidepressants (e.g. venlafaxine) is often neccessary. However, many of the antidepressants themselves may contribute to worsening or even development of the metabolic syndrome, thus creating a “vicious circle”. The aim of this work was to investigate on the animal model of metabolic syndrome, i.e. on hypertriacylglycerolemic rats fed high-fat-fructose diet (HFFD): 1) the effect of a change in diet from HFFD to a standard diet (SD) and the effect of venlafaxine treatment, 2) during HFFD, 3) as well as during a changed diet to SD. We focused on biometric parameters, blood pressure and selected ECG parameters. We observed the reversibility of the present metabolic and cardiovascular changes by switching the HFFD to SD in the last 3 weeks of the experiment. Switch to the standard diet led to decrease of body weight, even in the presence of venlafaxine. Administration of venlafaxine caused the decrease of heart weight/body weight index in rats fed with HFFD compared to the untreated group fed with HFFD for 8 weeks. Blood pressure, which was increased in the HFFD group showed a tendency to decrease to control values after switching to the standard diet. Administration of venlafaxine led to significant increase in all parameters of blood pressure when rats were fed with HFFD throughout the whole experiment. In untreated rats fed with HFFD for 8 weeks, we observed a shorter PQ interval and prolonged QRS complex as well as QTc interval compared to untreated rats with diet switched to SD. This effect was potentiated by venlafaxine administered not only during HFFD but even after switch to SD. Our results point to the fact that metabolic syndrome is clearly affecting the function of the cardiovascular system by modifying blood pressure and electrical activity of the heart. Moreover, administration of venlafaxine may lead to worsening of the observed changes, especially in the presence of high-fat-fructose diet.

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“…[25] opisuju primjer osobe ženskog pola (60 godina) koja je liječena od depresije primjenom terapijskih doza venlafaksina sa pojavom sindroma produženog QTc intervala (582 ms). Terapijsko dozno zavisno produženje QTc intervala primjenom venlafaksina navodi i Bavle [26], dok nije uočeno produženje QTc intervala nakon terapijske administracije venlafaksina kod djece [27]. U našoj studiji su takođe korišćene terapijske doze preporučne od strane proizvođača (venlafaksin dva puta dnevno po 37,5 mg), i nismo uočili statistički značajne razlike u dužini QT intervala (p = 0,827) (Tabela 1), iako se radilo o populaciji pacijenata osjetljivih na toksična dejstva lijekova zbog oštećenja jetre uslijed alkoholizma.…”

Section: Diskusijaunclassified

Analysis of effect of antidepressant drug venlafaxine on length of QT interval in patients with depressive disorder and alcohol dependence

Vukadinović-Stojanović¹,

Stojanović²

2019

Biomedicinska istraž.

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Uvod. Depresivni poremećaj je čest kod pacijenata sa dijagnozom alkoholizma.Komorbiditet depresije i alkoholizma umnogome pogoršava kliničko stanje pacijenta i predstavlja veliki terapijski izazov. Cilj ovog istraživanja je bio da se istraži dejstvo antidepresivnog lijeka venlafaksina na dužinu QT intervala pacijenata sa depresivnim poremećajem i alkoholnom zavisnošću.Metode. Istraživanjem je obuhvaćeno 49 pacijenata muškog pola (starijiod 18 godina) s alkoholnom zavisnošću kod kojih je na početku hospitalizacije na osnovu DSM-IV kriterijuma i pozitivne Hamiltonove skale za procjenudepresije (HRSD) dijagnostikovan depresivni poremećaj. Pacijentimaje ordiniran antidepresivni lijek venlafaksin, u dozi 37,5 mg, dva putadnevno, tokom dvadeset dana. Globalni QTc interval (12-odvodni) određivanje automatski primjenom EKG aparata Schiller Cardiovit AT-1 koji koristi“SCHILLER ECG Measurement and Interpretation Software for Childrenand Adult ECGs”. Statistička obrada podataka urađena je u SPSS 16.0 programskompaketu za Windows.Rezultati. Uočena je statistički značajna pozitivna povezanost između HRSDskora (intenziteta depresije) i koncentracije kreatin kinaze izoenzima MB userumu tj. stepena oštećenja miokarda (p = 0,048). Statistički značajna pozitivnapovezanost utvrđena je između koncentracije gama glutamil transferazeu serumu i dužine QTc intervala (p < 0,001.) Nije utvrđena statističkiznačajna razlika u dužini QTc intervala prije i nakon ordiniranja venlafaksina(p = 0,827), a prosječno produženje QTc intervala bilo je 0,776 ms (95%CI = -6,323 ms − 7,874 ms).Zaključak. U našoj studiji nismo utvrdili negativan uticaj antidepresivnoglijeka venlafaksina na dužinu QT intervala pacijenata sa depresivnim poremećajemi alkoholnom zavisnošću. Kod pacijenata ovisnika o alkoholuterapija depresije mora imati prioritet zbog ustanovljene negativne povezanostiizmeđu depresije i stepena oštećenja miokarda.

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Venlafaxine induced QTc interval prolongation in a therapeutic dose

Cited by 13 publications

References 7 publications

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

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

The effect of venlafaxine on blood pressure and ECG in rats fed with high-fat-fructose diet

Analysis of effect of antidepressant drug venlafaxine on length of QT interval in patients with depressive disorder and alcohol dependence

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