Antidepressant black box warnings intended to reduce suicide risks might be inadvertently amplifying those risks, suggests a new study.
The bold, black-outlined caution notice, commonly referred to as the "boxed warning," is seen on some medication labels or pamphlets. Its purpose is to draw attention to potential risks linked to the drug and boost physicians' surveillance of potential suicidal tendencies.
However, recent investigations suggest that boxed warnings associated with antidepressants may have unwanted consequences on pediatric health care and suicidality. The study, published on Monday in Health Affairs, indicates a decrease in mental health care services and increases in psychotropic drug overdoses and suicide rates among children, as per the comprehensive analysis. (Psychotropic drugs or other substances impact the brain's functioning, resulting in changes in mood, cognition, emotions, or behavior.)
Lead study author Dr. Stephen Soumerai, professor at the Harvard Pilgrim Health Care Institute and Harvard Medical School in Massachusetts, said in a press release, "We aimed to examine the intended and unintended outcomes of youth antidepressant warnings by conducting a thorough analysis of the most reliable data in this field."
Researchers scrutinized all available reports on warnings, focusing on rigorously designed studies and synthesizing dependable data sources. The findings are based on 11 reports, including studies that evaluated immediate effects following the 2003 FDA advisory or the 2005 boxed warnings.
Some studies pointed out inadequate surveillance of suicidality. After the FDA advisory and warning, doctors monitored fewer than 5% of pediatric patients as recommended by the FDA, with similar monitoring rates as before the warning period. None of the studies reported improvements in mental health care or decreases in suicide attempts or deaths after the warnings were implemented.
Conversely, four studies involving more than 12 million patients revealed significant reductions in doctor visits for depression symptoms or diagnoses before the FDA advisory. There were sudden and sustained declines in antidepressant use—ranging from 20% to 50%—after the warnings were introduced.
Three studies revealed an increase in psychotropic drug poisonings, suggesting suicide attempts, and in suicide deaths among children. The effects of the warnings also impacted young adults aged 18 to 24.
"The rapid, widespread, and lasting effects of these warnings—reduced depression treatment and increased suicide—are seen across 14 years of solid research," Soumerai said. "The consistency in observed harms and lack of observed benefits after the Black-Box Warnings suggests this isn't a coincidence."
The FDA recommended further consideration of incorporating boxed warnings into routine warnings with lower health risks or possibly removing the warnings altogether, in response to a request for comment.
The new study doesn't establish a direct link between antidepressants or boxed warnings and suicidality, said Dr. Lisa Fortuna, chair of the Council on Children, Adolescents, and Their Families at the American Psychiatric Association, in an email. Fortuna wasn’t involved in the study.
Interpreting the findings
In the United States, depression is a significant contributor to suicide, and suicide is the second-leading cause of death among 10- to 14-year-olds and the third-leading cause of death among 15- to 24-year-olds, according to the National Institute of Mental Health.
Since the boxed warnings were implemented, psychiatric practices recommend treating moderate to severe depression in adolescents, conducting follow-ups within two weeks after starting antidepressant use, and similarly after any dose increase. Families must be warned about the warnings and educated about the relative risks of untreated depression compared to antidepressant side effects.
However, "the study strongly suggests that the Black Box warning may have made some providers and families concerned about treating adolescents with antidepressants," Fortuna said. "The FDA warnings aimed to enhance physician monitoring of suicidal thoughts and behavior, so it was surprising that this doesn't seem to be the case."
The absence of monitoring may also be due to overwhelmed clinical practices, Fortuna said. Many youth psychiatrists reported more depressed youth referrals from pediatricians due to concerns about prescribing antidepressants, but the demand for mental health care services exceeds the available providers.
It's vital to consider that increases in suicide rates may be due to factors beyond boxed warnings, Fortuna said, as "we are experiencing a mental health crisis in the United States, and there's been a lot of research on rising mental illness and suicidality over the past decade and escalating during the pandemic."
Exploring all potential causes in one study is challenging, but according to Fortuna, "the findings are at least worth considering seriously."
Moreover, the findings on sudden decreases in antidepressant use are technically based on declines in antidepressant prescription dispensation, said Dr. Kao-Ping Chua, associate professor of pediatrics at the Susan B. Meister Child Health Evaluation and Research Center at the University of Michigan Medical School. Chua wasn't involved in the study.
However, it's unclear "whether this represents inappropriate antidepressant withholding from young people with severe depression versus cessation of antidepressant therapy in young people who no longer needed the medication," Chua added in an email.
Another drawback is that the analysis primarily examined the immediate to intermediate impacts of a warning issued two decades ago, Chua mentioned.
"We're unsure if these impacts have persisted," he continued. "There's reason to believe they haven't. For instance, our prior research revealed an aggressive increase in antidepressant prescription among female teenagers and young adults during the COVID-19 period — an increase that emerged despite an FDA black box warning being active."
Managing your kid's depressive episodes
If you detect significant alterations in your kid's behavior or emotions — like changes in their sleep patterns, social life, attitude, academic performance, focus or enthusiasm for activities — they might be battling depression. Dealing with these symptoms can be a complicated task, fraught with worry about treating symptoms while avoiding additional risk to the kids.
"It's undeniable that the decision to introduce antidepressant therapy ought not be taken lightly, but frankly, that's true for any long-term medication," Chua stated. "All medications have potential advantages and disadvantages. The issue is whether the advantages are likely to surpass the disadvantages."
Various therapies and treatments ought to be explored with a healthcare expert who invests time in discussing the benefits and drawbacks with both the youths and their family members, enabling a well-informed choice, Chua suggested.
"No topic should be off-limits," Fortuna said. "I also believe that the FDA's intent to bolster physician scrutiny of suicidal thoughts and behaviors through the warnings is valid."
Young individuals struggling with depression ought to "undergo comprehensive assessment and be closely monitored whether they've commenced antidepressants or not, yet particularly if they've been prescribed medicine," she added.
Usual side effects usually subside within a couple of weeks or so, and if they don't, a medical professional may propose a different medication. Every young person varies in terms of risk level, requirements, and situations, Fortuna pointed out, and antidepressants can be life-saving.
The study suggests that boxed warnings on antidepressants may negatively impact pediatric mental health care, leading to decreases in depression care services and increases in psychotropic drug overdoses and suicide rates among children. Despite the boxed warnings' purpose of enhancing physician monitoring of suicidal thoughts, researchers found that doctors monitored fewer than 5% of pediatric patients as recommended.
The findings indicate that the boxed warnings may be causing providers and families to be concerned about treating adolescents with antidepressants, potentially leading to reduced depression treatment and increased suicides. However, it's important to note that the study does not establish a direct link between antidepressants and suicidality, and other factors, such as the mental health crisis in the United States, could be contributing to the increase in suicide rates.
