The Effect of Venlafaxine on Electrocardiogram Intervals During Treatment for Depression in Older Adults

Behlke, Lauren M.; Lenze, Eric J.; Pham, Vy; Miller, J. Philip; Smith, Timothy W.; Saade, Yasmina; Karp, Jordan F.; Reynolds, Charles F.; Blumberger, Daniel M.; Stefan, Cristiana; Mulsant, Benoit H.

doi:10.1097/jcp.0000000000001287

Cited by 8 publications

(15 citation statements)

References 46 publications

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“…At therapeutic levels, venlafaxine has a thirty times higher affinity for serotonin receptors than noradrenaline receptors [20]. Venlafaxine may cause mild tachycardia, headache, dry mouth, increased HR and BP, decreased HRV, QTc prolongation, and TdP at higher doses by blockage of cardiac sodium channels, it acts like an SSRI at lower doses but is more efficacious at higher doses, so when it is prescribed in treatment-resistant depression, PTSD, generalized anxiety disorders (GAD), panic disorders close monitoring is advised to prevent adverse cardiac events like tachyarrhythmias, hypertensive crisis, angina, extra-systoles, CHF and SCD [2,6,[8][9][10]15,16,[20][21][22]. Inhibition of cardiac and vascular Ca2+, K+, and Na+ channels by SSRIs and SNRIs may be associated with cardiac adverse events in susceptible patients [23].…”

Section: Venlafaxine Mechanism Of Action Regarding Toxicity Genetics ...mentioning

confidence: 99%

“…Venlafaxine is an SNRI and has dual serotonergic and noradrenergic activity, it is one of the most frequently prescribed anti-depressants in SSRI non-responders, many of these patients have co-morbid cardiovascular disease [ 15 ]. Noradrenergic reuptake inhibition is attributed to its effectiveness at doses higher than 150 mg/day [ 15 ].…”

Section: Reviewmentioning

confidence: 99%

“…Behlke et al reported that venlafaxine did not prolong QTc [ 15 ]. QTc is a proxy marker for drug-induced SCD risk [ 15 ].…”

Section: Reviewmentioning

confidence: 99%

“…Behlke et al reported that venlafaxine did not prolong QTc [ 15 ]. QTc is a proxy marker for drug-induced SCD risk [ 15 ]. Preclinical studies of venlafaxine showed no significant QTc prolongation [ 15 ].…”

Section: Reviewmentioning

confidence: 99%

“…QTc is a proxy marker for drug-induced SCD risk [ 15 ]. Preclinical studies of venlafaxine showed no significant QTc prolongation [ 15 ]. Clinical studies haven’t been as conclusive for venlafaxine and suggest QTc prolongation may occur at higher rates than previously expected due to cytochrome enzyme CYPD26 variations and drug-drug interactions [ 15 ].…”

Section: Reviewmentioning

confidence: 99%

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The Risk of Fatal Arrhythmias in Post-Myocardial Infarction Depression in Association With Venlafaxine

Gutlapalli¹,

Lavu²,

Mohamed³

et al. 2022

Cureus

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Venlafaxine is a second line anti-depressant and the most commonly used in the treatment of selective serotonin reuptake inhibitor nonresponders in major depression; due to its effects on the noradrenergic and serotonergic systems as a serotonin and norepinephrine reuptake inhibitor, there has been considerable apprehension regarding its use in patients with cardiovascular diseases, particularly post-myocardial infarction depression, some of the feared adverse effects include QT prolongation, arrhythmias including torsades de pointes and sudden cardiac death. We tried to resolve the facts regarding the risks associated with venlafaxine use in cardiac patients. We have reviewed all the relevant information up to May 2022 regarding the risks of venlafaxine use in cardiovascular disease, particularly with a focus on post-myocardial infarction depression, and gathered around 350 articles in our research and narrowed it down to 49 articles. The database used was PubMed and the keywords used were venlafaxine, arrhythmia, major depression, post-myocardial infarction, and ventricular tachycardia. We carefully screened all relevant articles and found articles supporting and refuting the effects of venlafaxine in increasing cardiovascular morbidity and mortality. We have concluded that there is a significant variability due to confounding factors affecting individual cases. Overall there is no increased arrhythmia risk in comparison with other anti-depressants except in high-risk cases such as with pre-existing cardiovascular disease, certain genotypes, and other comorbidities. Any patient with a high risk of arrhythmias due to any etiology should receive a screening electrocardiogram before venlafaxine prescription for baseline QT interval and periodically while on therapy to check for changes. We encourage further research, including randomized clinical trials and postmarketing surveillance regarding the use of venlafaxine in high-risk cases such as patients with multiple comorbidities, elderly patients, or patients with certain genotypes.

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Section: Venlafaxine Mechanism Of Action Regarding Toxicity Genetics ...mentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

“…Behlke et al reported that venlafaxine did not prolong QTc [ 15 ]. QTc is a proxy marker for drug-induced SCD risk [ 15 ].…”

Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

See 3 more Smart Citations

The Risk of Fatal Arrhythmias in Post-Myocardial Infarction Depression in Association With Venlafaxine

Gutlapalli¹,

Lavu²,

Mohamed³

et al. 2022

Cureus

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CYP2D6 Phenotype Influences Pharmacokinetic Parameters of Venlafaxine: Results from a Population Pharmacokinetic Model in Older Adults with Depression

Men,

Taylor,

Marshe

et al. 2024

Clin Pharma and Therapeutics

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In this study, we aimed to improve upon a published population pharmacokinetic (PK) model for venlafaxine (VEN) in the treatment of depression in older adults, then investigate whether CYP2D6 metabolizer status affected model‐estimated PK parameters of VEN and its active metabolite O‐desmethylvenlafaxine. The model included 325 participants from a clinical trial in which older adults with depression were treated with open‐label VEN (maximum 300 mg/day) for 12 weeks and plasma levels of VEN and O‐desmethylvenlafaxine were assessed at weeks 4 and 12. We fitted a nonlinear mixed‐effect PK model using NONMEM to estimate PK parameters for VEN and O‐desmethylvenlafaxine adjusted for CYP2D6 metabolizer status and age. At both lower doses (up to 150 mg/day) and higher doses (up to 300 mg/day), CYP2D6 metabolizers impacted PK model‐estimated VEN clearance, VEN exposure, and active moiety (VEN + O‐desmethylvenlafaxine) exposure. Specifically, compared with CYP2D6 normal metabolizers, (i) CYP2D6 ultra‐rapid metabolizers had higher VEN clearance; (ii) CYP2D6 intermediate metabolizers had lower VEN clearance; (iii) CYP2D6 poor metabolizers had lower VEN clearance, higher VEN exposure, and higher active moiety exposure. Overall, our study showed that including a pharmacogenetic factor in a population PK model could increase model fit, and this improved model demonstrated how CYP2D6 metabolizer status affected VEN‐related PK parameters, highlighting the importance of genetic factors in personalized medicine.

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The Cardiovascular Effects of Newer Antidepressants in Older Adults and Those With or At High Risk for Cardiovascular Diseases

2020

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Depression is common in older adults and those with cardiovascular disease. Although serotonin reuptake inhibitors (SSRIs) generally have been shown to be safe to treat depression in these patients, it is important to identify additional antidepressants when SSRIs are not effective. This qualitative narrative review summarizes what is known about the cardiovascular side effects of some of the newer antidepressants.

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The Effect of Venlafaxine on Electrocardiogram Intervals During Treatment for Depression in Older Adults

Cited by 8 publications

References 46 publications

The Risk of Fatal Arrhythmias in Post-Myocardial Infarction Depression in Association With Venlafaxine

The Risk of Fatal Arrhythmias in Post-Myocardial Infarction Depression in Association With Venlafaxine

CYP2D6 Phenotype Influences Pharmacokinetic Parameters of Venlafaxine: Results from a Population Pharmacokinetic Model in Older Adults with Depression

The Cardiovascular Effects of Newer Antidepressants in Older Adults and Those With or At High Risk for Cardiovascular Diseases

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