We undertook a system-wide evaluation of the treatment of depressive and anxiety disorders in children and adolescents in Manitoba in the 9 years before and the 2 years following the Health Canada warning about the use of antidepressants in this age group. Our findings suggest that the warning not only affected prescribing patterns of the drugs mentioned in the warning but that it also had spillover effects on the provision of care for indications and populations not targeted by the warning. We found a 14% decrease in the rate of antidepressant prescription among children and adolescents after the warning. The rates of use of newer antidepressants, excluding fluoxetine, decreased by 32%–40%. Fluoxetine use increased by 10% in the period following the warning. During the same period, the rate of antidepressant prescription decreased by 10% among young adults, a patient population that was not targeted by the warning. In addition, we found that the rate of physician visits because of depression decreased in both age groups. This finding indirectly suggests that psychotherapy (at least as provided by physicians) did not replace the absent pharmacotherapy.
We found that the rate of completed suicides among children and adolescents increased by 25% following the warning. There was no such change among young adults. We found no change in the rates of suicide attempts that required hospital admission or in the rates of hospital admission because of depression among either children and adolescents or young adults.
In our subanalysis we found that the Health Canada warning was not associated with changes in antidepressant prescription rates among children and adolescents with anxiety disorders, except for a decrease in the prescription of selective serotonin reuptake inhibitors other than fluoxetine. Similarly, there was no significant change in the rate of physician visits among children and adolescents with anxiety disorders in the period after the warning. Among young adults with anxiety disorders, however, we found that the rate of antidepressant prescription was similar to the pattern of changes in the overall prescribing of antidepressants. There was also a significant decrease in the rate of physician visits because of anxiety disorders among young adults after the warning.
Our study raises several questions about the impact of warnings from regulatory bodies. First, as in other studies,
1,3–5 we found a decrease in the rates of antidepressant prescription both among children and adolescents and among young adults in the period following the Health Canada warning. The regulatory bodies stated that their intent was not to discourage prescribing;
17 nevertheless it did occur in association with the warnings. Furthermore, we found decreased prescribing among young adults, a population that was not targeted by the Health Canada warning. This supports the findings of Valuck and colleagues,
8 who demonstrated similar spillover effects. Second, we found a decrease in the rate of physician visits because of depressive disorders among children, adolescents and young adults as well as a decrease in the rate of visits because of anxiety disorders among young adults. These findings are similar to those of other studies that documented decreases in treatment episodes for depression in children and adolescents and young adults in association with regulatory warnings in the United States.
8,9 It is of concern that, in an environment where the treatment of a life-threatening disorder has become more complicated, vulnerable patients are receiving less care. Richardson and colleagues
18 reported that attitudes of health care providers toward the treatment of depression in adolescents have not changed, which suggests that the changes in the treatment of depression observed in the United States may have been related to patient and family variables. It may also be that the warnings and the media response invoked fear of diagnosis and treatment among patients and their families.
19 Furthermore, Richardson and colleagues
18 found that providers had not changed their practices to meet the guidelines regarding monitoring of patients recommended in association with the warnings. This is similar to the impact of regulatory action on prescribing practices in the use of cyclooxygenase-2 inhibitors. Following the withdrawal of rofecoxib, there was a decrease in prescribing of cyclooxygenase-2 inhibitors; however, physicians did not follow the recommended guidelines for alternative treatments.
20,21The increased rate of suicide that we observed among children and adolescents in the period following the Health Canada warning is of concern, especially because it coincided with a decrease in the rate of physician visits for the treatment of depressive and anxiety disorders. Our finding is similar to that of Gibbons and colleagues,
5 who reported an association between the regulatory warning in the United States and an increased suicide rate among children and adolescents. We are unable to draw conclusions about whether the decrease in treatment of depressive and anxiety disorders caused the increase in suicides; we can merely document an association between the regulatory warning and an increase in the suicide rate. Factors other than antidepressant prescribing may be responsible for the observed changes. Furthermore, only 2 years of data were available after the warning for our analysis, and conclusions on whether this finding indicates a trend or an anomaly would be premature. Collectively, however, our observations raise concerns over the potential for the regulatory warning to lead to untreated depression and other related mental health issues. The vast majority of children and adolescents who completed suicide had not received an antidepressant before the time of death, a finding supported by a review of autopsy results for the children and adolescents who completed suicide after the warning (unpublished data). This finding is also consistent with results from other studies of suicide among youth taking antidepressants.
22–24We postulate that the observed changes following the warning would not be confined to a single Canadian jurisdiction or regulatory authority. Indeed, other studies have consistently documented changes in the use of antidepressants, but none has documented such a wide range of unintended health consequences.
Our study has limitations beyond those described above. First, physician coding of diagnoses may not have been accurate in all cases, and the prescription data may not have reflected actual use. Second, the validity of the diagnosis of suicide is impossible to ascertain, a problem inherent to the study of suicide.
In conclusion, the warning issued by Health Canada about the use of antidepressants in children and adolescents was associated with a decrease in the use of the targeted medications. However, the warning had important and unintended adverse consequences on the delivery of health services to patients with depressive and anxiety disorders, both those targeted and not targeted by the warning. Given the potentially devastating consequences of some health warnings, greater attention must be paid to optimal dissemination strategies for health advisories and warnings. Regulatory bodies should conduct timely evaluations of major health warnings to ensure that they have the desired effects and, if not, to institute appropriate corrective measures.
@ See related article page 1025
This article has been corrected. See 
