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Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system

BMJ 2017; 356 doi: (Published 21 February 2017) Cite this as: BMJ 2017;356:j603

Re: Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system

For our non-Canadian colleagues, I would first provide the context that in Canada, only family doctors/general practitioners are considered primary care physicians. Physicians of all other specialties are considered specialists and would therefore not be included in this study.

Secondly, while the evidence surrounding the effectiveness of antidepressants in non-severe depression over other modes of therapy is perhaps not as weak in adults as it is in children or adolescents (Cox et al., 2014), we should remember that many of our guidelines are not based on immutable data that has been consistently repeated and that publication bias is a very real consideration (Turner, Matthews, Linardatos, Tell, & Rosenthal, 2008). The controversy surrounding multiple Joint National Committee (JNC) guidelines on hypertension serve as some well-known examples. By nature, science is iterative and we will always have a need for additional strong, robust studies that are both reflective of our real-world populations and reproduced by other investigators. This is the basis of the scientific method. However, we would be remiss to throw the baby out with the bath water.

In this age of ever-expanding scopes of practice, a growing top-down pressure to blindly follow guidelines also coexists in some healthcare systems. With so much data - and much of it apparently conflicting on the surface - this blind adherence to a specific single guideline ("The Chosen One") is dangerous. As primary care physicians, it is our responsibility to critically assess the data supporting our practices. Furthermore, we must bear in mind that many studies are conducted with very specific exclusion criteria not representative of our typical patient populations. Additionally, the conclusions of such studies are primarily applicable to a population-level perspective, not to any one specific patient. In this context, our true value lies in our ability to evaluate and determine the primary and other related issues and meaningfully apply the best science available in consideration of the unique individual sitting before us. This includes always weighing the potential benefits of treatment against the possible risks.

While I can appreciate the challenge in determining on a large scale whether or not prescriptions were on-label, it was interesting to read that evaluation of the appropriateness of physician prescribing patterns was done by applying rules that may have only existed months, years, or even a decade after a prescription was filled. This is the situation described under Measurements, where "approved indications were determined at the end of the study period rather than the year in which the prescription was written so that all prescriptions would be classified using the same benchmark." Under this rule, a medication that was on-label when prescribed would be classified as inappropriate/off-label in this study if the approved indication changed over the 12.5 years of the study.

Similarly, while only a small percentage were apparently affected, the subsequent decision to go with an "all or nothing" marking scheme was also interesting: "If a physician recorded multiple indications for the drug (n=1922, 1.8% of all antidepressant prescriptions), the prescription was classified as off-label only if all the indications were not approved." In other words, a medication ordered with multiple indications would be marked as appropriate only if all of the indications were on-label at the end of the study. One strike of the baseball and you are out of the quidditch match.


Cox, G., Callahan, P., Churchill, R., Hunot, V., Merry, S., Parker, A., & Hetrick, S. (2014). Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents. Cochrane Database Of Systematic Reviews.

Turner, E., Matthews, A., Linardatos, E., Tell, R., & Rosenthal, R. (2008). Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. New England Journal Of Medicine, 358(3), 252-260.

Competing interests: No competing interests

01 March 2017
Raj Bhui
Family Medicine physician
University of British Columbia
British Columbia, Canada