Drs. Hasnain, Howland and Vieweg1 have queried the issue of QTc risks of escitalopram versus citalopram. Of course, in a brief column it is difficult to pay justice to a complex topic, which is why I referenced some of their excellent publications on this topic. However, I note that they have previously raised the issue of an exaggerated regulatory response to the citalopram QTc data. In fact, the first conclusion in their comprehensive 2012 review in the American Journal of Medicine was, “Contrary to the assertions of the manufacturer of citalopram and the FDA [U.S. Food and Drug Administration] published in August 2011, we found no convincing evidence that citalopram, when used as prescribed in doses above 40 mg/day, was associated with an increased risk of QTc interval prolongation and torsade de pointes [TdP], as long as clinicians attended to well-known risk factors. And this drug at a 60 mg dose is no more likely to induce QTc interval prolongation than such drugs as ziprasidone and quetiapine.”2
Given that Drs. Hasnain, Howland and Vieweg suggest that even citalopram has a low QTc risk, the question is not whether escitalopram has any risk, but rather how does that risk compare with that of other antidepressants and psychotropic medications, and how should clinicians deal with that risk? In this regard, they also note that, in contrast to Health Canada and the FDA, the Medicines and Healthcare Products Regulatory Agency in the United Kingdom issued a safety warning for both citalopram and escitalopram. The fact that several regulatory agencies reached different conclusions based on essentially the same data set suggests that the issue is complex and subject to non-evidence-based opinions. In Europe, the regulatory warnings have also been criticized as exaggerated responses by several professional and scientific societies.3,4 A pharmacovigilance study conducted by the Austrian Society of Drug Safety that included 57 911 patients treated with selective serotonin re-uptake inhibitors (SSRIs; 16 351 with citalopram and 14 319 with escitalopram) in Austria, Germany and Switzerland found only 7 adverse cardiac events that were considered to be related to therapy with SSRIs (3 with sertraline and 1 each with citalopram, fluoxetine, fluvoxamine and paroxetine).4 Only 2 cases of cardiac arrhythmia (1 with fluoxetine, 1 with sertraline), neither considered TdP, were identified. In this pharmacovigilance database, not a single case of escitalopram-induced adverse cardiac event was detected. Hence, there is little evidence of clinically significant adverse cardiac effects with escitalopram.
It is now recognized that there are often unintended consequences of regulatory agency warnings, as illustrated by the association with decline in diagnosis and treatment5 and increase in suicide rates,6 in the United States and Canada7 following the regulatory warnings related to suicidality and antidepressants in children and youth. It is important that patients not be deprived of appropriate, effective and safe treatments based on premature and unsupported risk assessments.
While many antidepressants can have effects on QTc, the clinical relevance is still questionable. Certainly there is not enough evidence to change clinical practice for prescribing these medications, except for the usual caution of being aware of potential cardiac risks, particularly when patients have several non-drug-related risk factors for QTc prolongation and TdP. As Drs. Hasnain, Howland and Vieweg also noted in their review, “A large body of experience and data attest to the clinical effectiveness and cardiac safety of citalopram. Truncating its use at this time seems premature at best.”2 I would underscore that a therapeutic dose of escitalopram carries no greater cardiac risk than any other antidepressant and has a lower risk than other psychotropics, such as haloperidol, quetiapine and ziprasidone.
Footnotes
Competing interests: Dr. Lam is on ad hoc Speaker/Advisory Boards for, or has received research funds from: AstraZeneca, Biovail, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Eli Lilly, Litebook Company, Lundbeck, Lundbeck Institute, Mochida, Pfizer, Servier, St. Jude’s Medical, Takeda, and UBC Institute of Mental Health/Coast Capital Savings.