The available data suggested that fenfluramine was the most commonly used appetite suppressant when data were collected. Since fenfluramine is no longer available in Canada, this has almost certainly changed since the time of data collection. Additional epidemiological data will be needed to determine whether the withdrawal of fenfluramine from the Canadian market has altered the association between the use of appetite suppressants and major depression. The advent of peripherally acting lipase inhibitors such as orlistat may also alter these epidemiological associations. Because these drugs have minimal absorption, they are unlikely to have substantial direct effects within the central nervous system. They may, however, have potentially relevant indirect effects (for example, by causing malabsorption of fat-soluble vitamins).

Despite these limitations, the results reported here are striking because of the dramatic magnitude of the association between these medications and major depression. Pharmacoepidemiological data are often useful for hypothesis generation. For example, the purported association between reserpine and major depression had an impact on the development of early neurobiological hypotheses about depression (14). It is possible that appetite suppressants elevate the risk of major depression through direct neurobiological mechanisms, as a feature of withdrawal (the discordance between a 1-month and 2-day measure of diet pill use in the NPHS suggests that the medications are often used intermittently), or as an artifact resulting from confounding with variables not measured in this survey. Reverse causal mechanisms are also possible: depressive disorders may cause a more negative evaluation of body image, leading indirectly to increased exposure to diet pills. These findings emphasize the need for caution in the use of appetite-suppressant medications and the need to further evaluate their association with depression.

Acknowledgement

Dr Patten is supported by a Population Health Investigator Award from the Alberta Heritage Foundation for Medical Research.

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