According to the results of this nested case control study published early online in the British Medical Journal (BMJ), the use of venlafaxine was not associated with a higher risk of sudden cardiac death or near death than fluoxetine, dosulepin, or citalopram, in patients with depression or anxiety.

The authors of the study note the cardiac cautions/contra-indications with venlafaxine, and advice issued by the MHRA in 2006 (revision of previous advice) that patients at very high risk of ventricular arrhythmia or with uncontrolled hypertension should not use venlafaxine.  They note that that there has to their knowledge been no systematic study evaluating the risk of haemodynamically significant (malignant) arrhythmias or sudden cardiac death associated with the use of venlafaxine in usual clinical practice. 

This population-based observational study was therefore conducted, using data obtained from the United Kingdom General Practice Research Database (GPRD).  The study cohort consisted of all adult new users (i.e. no prescription of the study drug in the year before cohort entry) of venlafaxine (n=19,268), fluoxetine (n=90,924), citalopram (n=53,300), or dosulepin (n=43,892), for depression or anxiety, after 1 January 1995 (total n=207,384).  Follow-up was until February 2005, or the occurrence of the study outcome (sudden cardiac death or near death), death, or transfer out of practice.  Each case was matched with up to 30 controls, matched for age, sex, cohort entry date and indication (depression and/or anxiety). 

There were 568 cases of sudden cardiac death or near death, including 27 acute ventricular tachyarrhythmias, 236 sudden cardiac deaths, and 305 out of hospital cardiac ischaemic deaths (these were matched to 14,812 controls).  The overall rate of sudden cardiac death or near death was 8.21 per 10,000 person-years.  The adjusted odds ratios of sudden cardiac death or near death associated with venlafaxine use were 0.66 (95% CI 0.38 to 1.14) relative to fluoxetine use, 0.89 (0.50 to 1.60) compared with citalopram, and 0.83 (0.46 to 1.52) compared to dosulepin.

The authors note that there was “no compelling evidence that venlafaxine was preferentially prescribed to patients with lower risk for cardiac events, consistent with the observation that adjustment for potential confounders had minimal effect on results.”  They note the various limitations of their study, mainly involving the lack of detail in the GPRD medical history and the “challenge of determining the precise sequence of events in patients who died out of hospital”.  

An accompanying editorial (by David Taylor, Chief Pharmacist at the South London and Maudsley NHS Foundation Trust) discusses the findings, in light of other evidence on the safety of venlafaxine.  He notes that the regulatory authorities (particularly in the UK) have been inconsistent with their advice on the safe prescribing of the drug.  He concludes that “for now, continued restriction on the use of venlafaxine on the grounds of cardiovascular toxicity seems inappropriate”.