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Health and Drug Alerts: Venlafaxine (Effexor): concerns about increased risk of fatal outcomes in overdose
CMAJ (Canadian Medical Association Journal)
January 2, 2007 176:39-40; published ahead of print December 13, 2006, doi:10.1503/cmaj.061533
By Thomas L Perry
Clinical Assistant Professor
Notification about the potentially fatal risk of venlafaxine in overdose is timely. Although the practice alert points out that both the mechanisms and the true relative risk of fatality from venlafaxine (vs. other antidepressants or no treatment) remain unclear, venlafaxine use continues almost as if it were innocuous.
Sworn evidence from the Chief Analyst for the B.C. Provincial Toxicology Centre during a recent criminal trial (1) suggests that venlafaxine may have contributed to well over 100 unanticipated deaths in British Columbia alone. Dr. Stuart Huckin testified that “there are probably only five or six deaths per year due to venlafaxine alone, but in conjunction with other drugs, (with) venlafaxine as the major cause of death, probably 30 deaths a year”. (2) Dr. Huckin also testified that this phenomenon was noted in the Provincial Toxicology Centre as early as the year 2000 – “…perhaps even before this, we had noticed that venlafaxine was causing a larger number of deaths than other anti-depressants.” (3)
Whether venlafaxine or its active metabolite depress ventilation, induce cardiac dysrhythmias, induce convulsions, or cause harm by alternative mechanism(s) remains unknown. It is also possible that venlafaxine is associated with more deaths because it remains fashionable to prescribe this drug to patients with “treatment resistant depression” or those in whom it is hoped that consumption of venlafaxine may avoid suicide. If so, the large numbers of deaths associated with this drug should give prescribers pause to reconsider whether venlafaxine is truly more efficacious than alternatives (including non-drug treatment) and to review the evidence about dose-responsiveness for this or any other depressants.
The belated and serendipitous surfacing in a law court of evidence about a significant epidemic of drug toxicity highlights Health Canada’s failure (and that of other drug regulatory agencies) to protect the public. Intensified and mandatory post-marketing surveillance of new drugs is long overdue.(4)
Given the intensification of drug marketing and “megapolypharmacy”, provincial Coroners Services might also save lives by publicizing information about prescription drugs learned from inquests and other routine investigations. Perhaps it is time for judicial and quasi-judicial agencies to rethink their definitions of the “War on Drugs” to include a broader spectrum of the public interest.
Thomas L. Perry, M.D. Department of Anesthesiology, Pharmacology & Therapeutics University of British Columbia
1. R. v. Swanney, 2006 BCSC 1766. http://www.courts.gov.bc.ca/jdb- txt/sc/06/17/2006bcsc1766.htm (accessed December 28, 2006).
2. Huckin, S. X068283-2 New Westminster Registry; Supreme Court of British Columbia. Regina v. James Swanney. New Westminster, B.C. March 14, 2006. (preliminary inquiry) page 29.
3. Huckin, S. X068283-2 New Westminster Registry; Supreme Court of British Columbia. Regina v. James Swanney. New Westminster, B.C. October 17, 2006. Proceedings at trial (Day 6)page 62.
4. Avorn J. Dangerous Deception — Hiding the Evidence of Adverse Drug Effects. N. Engl. J. Med. 2006; 355: 2169-2171.