A Comparison of the Risk of QT Prolongation Among SSRIs

Funk, Kylee A.; Bostwick, Jolene R.

doi:10.1177/1060028013501994

Cited by 131 publications

(94 citation statements)

References 78 publications

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“…However, the results of this study are contradictory to a previous FDA report (US Food and Drug Administration, 2012) on the effect of escitalopram on QT prolongation, in which the maximum mean (upper bound of 95% CI) ΔΔQTcF was 4.5 (6.4) and 10.7 (12.7) ms for 10 and 30 mg escitalopram administered once daily, respectively (US Food and Drug Administration, 2012). The US-FDA has issued a warning regarding the risk for QT prolongation for citalopram only (US Food and Drug Administration, 2012), whereas the UK-MHRA concluded the potential risk for QT prolongation for both, citalopram and escitalopram (Medicines and Healthcare Products Regulatory Agency, 2011;Funk and Bostwick, 2013 To evaluate the QT prolongation potential of escitalopram adequately, the delay between its pharmacokinetic profile and QT prolongation, as seen in this study (Fig. However, our results were positive for 20 mg escitalopram in terms of QT prolongation with upper bound of 95% CI above 10 ms and the maximum QT prolongation delayed 3 h after T max .…”

Section: Discussionmentioning

confidence: 99%

A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers

Kim

Lim

Lee

et al. 2016

International Clinical Psychopharmacology

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Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner.

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Section: Discussionmentioning

confidence: 99%

A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers

Kim

Lim

Lee

et al. 2016

International Clinical Psychopharmacology

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“…(138) Among the SSRIs, sertraline, fluoxetine, fluvoxamine, and paroxetine appear to be the safest to use in patients with HF because they are unlikely to prolong the QT interval. (139) When choosing which of these SSRIs to use, it is important to consider possible drug interactions via cytochrome P450 enzymes 3A4 (fluvoxamine) and 2D6 (fluvoxamine, fluoxetine, and paroxetine). In general, sertraline is a good choice in patients with HF because it is unlikely to cause QT prolongation and has a lower potential to interact with concomitant medications.…”

Section: Depressionmentioning

confidence: 99%

Symptom burden in heart failure: assessment, impact on outcomes, and management

et al. 2016

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Evidence-based management has improved long-term survival in patients with heart failure (HF). However, an unintended consequence of increased longevity is that patients with HF are exposed to a greater symptom burden over time. In addition to classic symptoms such as dyspnea and edema, patients with HF frequently suffer additional symptoms such as pain, depression, gastrointestinal distress, and fatigue. In addition to obvious effects on quality of life, untreated symptoms increase clinical events including emergency department visits, hospitalizations, and long-term mortality in a dose-dependent fashion. Symptom management in patients with HF consists of two key components: comprehensive symptom assessment and sufficient knowledge of available approaches to alleviate the symptoms. Successful treatment addresses not just the physical but also the emotional, social, and spiritual aspects of suffering. Despite a lack of formal experience during cardiovascular training, symptom management in HF can be learned and implemented effectively by cardiology providers. Co-management with palliative medicine specialists can add significant value across the spectrum and throughout the course of HF.

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“…6 Highlighting their expansive use, from 2007 to 2010, antidepressants were taken in the past 30 days in 10.8% of US adults. This represents more than a 4-fold increase, up from 2.4% in the period 1988-1994.…”

Section: Introductionmentioning

confidence: 99%

Risk of QT/QTc Prolongation Among Newer Non-SSRI Antidepressants

Jasiak

Bostwick

2014

Ann Pharmacother

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Based on the current literature, risk of QT/QTc prolongation with the majority of newer non-SSRI antidepressants at therapeutic doses is low. The highest risk for QT prolongation appears to exist in overdose situations with venlafaxine and bupropion. Given the few to nonexistent controlled studies and confounding variables present in case reports, it is difficult to draw conclusions on QT prolongation risk with many of the newer non-SSRI antidepressants.

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A Comparison of the Risk of QT Prolongation Among SSRIs

Cited by 131 publications

References 78 publications

A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers

A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers

Symptom burden in heart failure: assessment, impact on outcomes, and management

Risk of QT/QTc Prolongation Among Newer Non-SSRI Antidepressants

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