Antidepressant Use By Young People After FDA Warnings
Antidepressant Use By Young People After FDA Warnings
Whether or not a link exists between the use of antidepressant drugs and the emergence of suicidal ideation and behavior in a subset of young people, widely publicized warnings for antidepressants and suicidality could have intended and unintended effects. As hypothesized, we found substantial reductions in antidepressant use, and simultaneous, small increases in psychotropic drug poisonings, a validated measure of suicide attempts, among adolescents and young adults after the FDA warnings targeting youth and widespread media coverage. These results were consistent across our geographically diverse study sites. We did not observe increases in psychotropic drug poisonings among adults, who had smaller reductions in antidepressant use.
Our finding of reduced antidepressant use in young people is consistent with previous studies. Although the FDA extended the warnings to include young adults in May 2007, this single additional communication did not add to the effects of the 2003-04 widely publicized warnings; we did not observe further abrupt changes in antidepressant use among young adults or other age groups. After 2008, the downward trend in antidepressant use among adolescents reversed somewhat; however, utilization remained below 2004 levels. This change may mean that the initial effects of the warnings tapered off or that the May 2007 modification to the FDA messages increased antidepressant use. In the modified message, clinicians and the public were urged to consider the risk of antidepressants alongside the risk of not treating mood disorders.
Our study provides the first evidence that suicide attempts increased rather than decreased after the warnings. Relative increases in non-fatal psychotropic drug poisonings were 21.7% among adolescents and 33.7% among young adults in the second year after the warnings. These reflected absolute increases of 77 poisonings in our cohort of 2.5 million young people (22 and 55 additional poisonings among adolescents and young adults, respectively; 2 and 4 additional poisonings per 100 000 people). The estimated excess risk of suicide attempt is an underestimate because it is based only on the second year of follow-up and does not include other means of suicide attempts. Since the increase in suicide attempts by poisoning was simultaneous with the significant reductions in antidepressant use, it might be one consequence of under-treatment of mood disorders. This explanation is bolstered by other studies that have found no compensating increases in the use of treatment alternatives among young people.
Our study was the first to examine the effects of the warnings on completed suicides over a long period. In contrast with the increases in suicide attempts, even with large sample sizes we observed no changes in suicides after the warnings. Completed suicides are rare; only one tenth as common as suicide attempts. Nevertheless, our data are consistent with the Centers for Disease Control and Prevention report that showed gradual increases in completed suicides between 1999 and 2010, without sudden discontinuities around the time of the FDA warnings and media reports, among people aged 10-34 years.
It is possible that the warnings and extensive media attention led to unexpected and unintended population level reductions in treatment for depression and subsequent increases in suicide attempts among young people. FDA advisories and boxed warnings can be crude and inadequate ways to communicate new and sometimes frightening scientific information to the public. Also, the information may be oversimplified and distorted when communicated in the media. However, we know that the media can influence drug use behavior in positive ways. For example, high profile news reports substantially reduced aspirin use in children and helped eradicate Reye’s syndrome. Greater efforts are needed to improve risk communications to the public and to health professionals. Active surveillance should be considered to allow timely detection and prompt actions to reduce unintended consequences of strong warnings.
We used an interrupted time series design, which is robust against most threats to internal validity. This study design controls for secular trends in study outcomes (for example, the apparent growing epidemic in use of prescription psychotropic drugs outside FDA approved indications) and thereby can attribute abrupt changes to the widely publicized warnings.
Several limitations of this study merit discussion. Firstly, as in other studies using administrative data, we were only able to measure psychotropic drug poisonings that were related to receipt of medical attention, thereby underestimating the true impact of the warnings on suicidality because only about a third of suicide attempts are medically treated. Secondly, we elected not to use deliberate self harm E-codes because they are incompletely coded across sites in the Mental Health Research Network and in commercial plan databases generally. Thirdly, we elected not to use a validated algorithm based on a combination of diagnoses of injury and psychiatric conditions, including depression, to avoid introducing ascertainment bias because previous research found that the rates of depression diagnosis declined after the warnings. Instead, we used psychotropic drug poisonings to estimate changes in suicide attempts after the warnings. While the positive predictive value of psychotropic drug poisonings is lower than the abovementioned algorithm (79.7% v 87.8%), it outperforms other injury and poisoning types and has high specificity. Given that each method only accounts for a small subset of suicide attempts, which are rare, we would not be able to detect any change in population level rates of suicide attempts by other means even with our large sample of 7.5 million. Because psychotropic drug poisonings account for about 38% of suicide attempts, our results underestimate increases in suicide attempts after the warnings. Further, our sample largely included insured populations (commercial plans and public insurers); the findings may not reflect behavior among uninsured patients. Our data sources did not have reliable information on socioeconomic status and race or ethnicity for the early 2000s, thus we did not stratify our analyses by these factors. Finally, our interrupted time series of population rates cannot be used to make inferences about patient level outcomes. Notwithstanding these limitations, given our study’s quasi-experimental design with long term follow-up, we provide rigorous evidence that the FDA warnings and media coverage led to substantial reductions in antidepressant use, which were associated with small increases in suicide attempts by poisonings among young people.
Undertreated mood disorders can have severe negative consequences. Thus, it is disturbing that after the health advisories, warnings, and media reports about the relation between antidepressant use and suicidality in young people, we found substantial reductions in antidepressant treatment and simultaneous, small but meaningful increases in suicide attempts. It is essential to monitor and reduce possible unintended effects of FDA warnings and media reporting.
Discussion
Whether or not a link exists between the use of antidepressant drugs and the emergence of suicidal ideation and behavior in a subset of young people, widely publicized warnings for antidepressants and suicidality could have intended and unintended effects. As hypothesized, we found substantial reductions in antidepressant use, and simultaneous, small increases in psychotropic drug poisonings, a validated measure of suicide attempts, among adolescents and young adults after the FDA warnings targeting youth and widespread media coverage. These results were consistent across our geographically diverse study sites. We did not observe increases in psychotropic drug poisonings among adults, who had smaller reductions in antidepressant use.
Our finding of reduced antidepressant use in young people is consistent with previous studies. Although the FDA extended the warnings to include young adults in May 2007, this single additional communication did not add to the effects of the 2003-04 widely publicized warnings; we did not observe further abrupt changes in antidepressant use among young adults or other age groups. After 2008, the downward trend in antidepressant use among adolescents reversed somewhat; however, utilization remained below 2004 levels. This change may mean that the initial effects of the warnings tapered off or that the May 2007 modification to the FDA messages increased antidepressant use. In the modified message, clinicians and the public were urged to consider the risk of antidepressants alongside the risk of not treating mood disorders.
Our study provides the first evidence that suicide attempts increased rather than decreased after the warnings. Relative increases in non-fatal psychotropic drug poisonings were 21.7% among adolescents and 33.7% among young adults in the second year after the warnings. These reflected absolute increases of 77 poisonings in our cohort of 2.5 million young people (22 and 55 additional poisonings among adolescents and young adults, respectively; 2 and 4 additional poisonings per 100 000 people). The estimated excess risk of suicide attempt is an underestimate because it is based only on the second year of follow-up and does not include other means of suicide attempts. Since the increase in suicide attempts by poisoning was simultaneous with the significant reductions in antidepressant use, it might be one consequence of under-treatment of mood disorders. This explanation is bolstered by other studies that have found no compensating increases in the use of treatment alternatives among young people.
Our study was the first to examine the effects of the warnings on completed suicides over a long period. In contrast with the increases in suicide attempts, even with large sample sizes we observed no changes in suicides after the warnings. Completed suicides are rare; only one tenth as common as suicide attempts. Nevertheless, our data are consistent with the Centers for Disease Control and Prevention report that showed gradual increases in completed suicides between 1999 and 2010, without sudden discontinuities around the time of the FDA warnings and media reports, among people aged 10-34 years.
Policy Implications
It is possible that the warnings and extensive media attention led to unexpected and unintended population level reductions in treatment for depression and subsequent increases in suicide attempts among young people. FDA advisories and boxed warnings can be crude and inadequate ways to communicate new and sometimes frightening scientific information to the public. Also, the information may be oversimplified and distorted when communicated in the media. However, we know that the media can influence drug use behavior in positive ways. For example, high profile news reports substantially reduced aspirin use in children and helped eradicate Reye’s syndrome. Greater efforts are needed to improve risk communications to the public and to health professionals. Active surveillance should be considered to allow timely detection and prompt actions to reduce unintended consequences of strong warnings.
Strengths and Limitations of This Study
We used an interrupted time series design, which is robust against most threats to internal validity. This study design controls for secular trends in study outcomes (for example, the apparent growing epidemic in use of prescription psychotropic drugs outside FDA approved indications) and thereby can attribute abrupt changes to the widely publicized warnings.
Several limitations of this study merit discussion. Firstly, as in other studies using administrative data, we were only able to measure psychotropic drug poisonings that were related to receipt of medical attention, thereby underestimating the true impact of the warnings on suicidality because only about a third of suicide attempts are medically treated. Secondly, we elected not to use deliberate self harm E-codes because they are incompletely coded across sites in the Mental Health Research Network and in commercial plan databases generally. Thirdly, we elected not to use a validated algorithm based on a combination of diagnoses of injury and psychiatric conditions, including depression, to avoid introducing ascertainment bias because previous research found that the rates of depression diagnosis declined after the warnings. Instead, we used psychotropic drug poisonings to estimate changes in suicide attempts after the warnings. While the positive predictive value of psychotropic drug poisonings is lower than the abovementioned algorithm (79.7% v 87.8%), it outperforms other injury and poisoning types and has high specificity. Given that each method only accounts for a small subset of suicide attempts, which are rare, we would not be able to detect any change in population level rates of suicide attempts by other means even with our large sample of 7.5 million. Because psychotropic drug poisonings account for about 38% of suicide attempts, our results underestimate increases in suicide attempts after the warnings. Further, our sample largely included insured populations (commercial plans and public insurers); the findings may not reflect behavior among uninsured patients. Our data sources did not have reliable information on socioeconomic status and race or ethnicity for the early 2000s, thus we did not stratify our analyses by these factors. Finally, our interrupted time series of population rates cannot be used to make inferences about patient level outcomes. Notwithstanding these limitations, given our study’s quasi-experimental design with long term follow-up, we provide rigorous evidence that the FDA warnings and media coverage led to substantial reductions in antidepressant use, which were associated with small increases in suicide attempts by poisonings among young people.
Conclusions
Undertreated mood disorders can have severe negative consequences. Thus, it is disturbing that after the health advisories, warnings, and media reports about the relation between antidepressant use and suicidality in young people, we found substantial reductions in antidepressant treatment and simultaneous, small but meaningful increases in suicide attempts. It is essential to monitor and reduce possible unintended effects of FDA warnings and media reporting.