Recent data have revealed that overdoses involving antidepressants have been climbing each year from 1999 until 2022 in the US, but the experts say the reasons are unclear.
The analysis was released last month, as it takes the organisation more than a year to process overdose data; 2022 is the most recent year with complete overdose data available, reports The Guardian.
Antidepressants were an underlying cause of death in 5 863 overdoses that year – a number on par with heroin-involved overdoses, which killed 5 871 people in the same year. These represent a small but significant percentage of climbing overdose deaths – more than 100 000 total in 2022, mostly from fentanyl.
Annual reports from the National Poison Data System, which compiles data from the US’s 55 poison centres, also show that poisonings involving antidepressants have risen consistently each year that the organisation released an annual report, from 2012 to 2022.
While the vast majority of fatal events with the medication involve other substances as well, 56 people died of antidepressant exposure alone in 2022, the highest number on record.
These numbers have been climbing for as long as data have been available and it’s hard to say exactly why. There’s information missing from the data, including the precise mixture of substances involved in each death, which makes it unclear how many are the result of suicide.
Phil Cowen, a psychopharmacology professor at the University of Oxford, said the rise was likely to be linked to the opioid epidemic in the United States.
“Overdose deaths from antidepressants without opioid involvement have been fairly steady; however, there is an increase in deaths where both antidepressants and opioids are involved,” he said.
Cowen added that patients who experience chronic pain and those with clinical depression are more likely to die by suicide. “These patients are also more likely to be on an opioid and an antidepressant.”
Multiple pharmacology experts contacted by The Guardian for this story suggested that this increase in overdoses could simply be due to an increase in antidepressant prescriptions.
While some felt that the level of overdoses was the logical outcome of more prescriptions, and therefore not a matter for concern, others worried that the increase of both prescriptions and overdoses illustrate the medical community’s failure to sufficiently acknowledge and address the risks of antidepressants.
The medication has been associated with numerous negative health outcomes, including an increase in premature mortality, according to a 2017 meta-analysis.
David Healy, a psychiatrist and psychopharmacologist at Bangor University who monitors the safety of prescription drugs, had a few theories on why overdoses have increased.
Previously, it was common to take antidepressants for just a few months. Now, many patients have been on them for many years, he said, which can elevate the risk for severe withdrawal and suicide attempts if they try to get off them. He added that doctors are increasingly unlikely to take patients seriously or take them off the medication when they report negative experiences on the medication.
Instead, Healy said, they are now prescribing additional psychotropic medications on top of the antidepressants. Sometimes patients will add alcohol or non-prescription opioids to the mix to balance out the negative effects of a cocktail of meds. All of these factors can increase the risk of accidental overdose or suicide attempt, Healy says, adding: “Between one thing or another, maybe being a little bit stuporous, they’ve taken more than they should and they end up dead.”
The risk of fatally overdosing on antidepressants alone is extremely low, although tricyclic antidepressants are riskier than others.
But antidepressants could increase patients’ risk of becoming suicidal, which could cause overdoses.
In 2004, the FDA introduced a black box label warning that antidepressants could lead to suicidality in adolescents and young adults. The label was controversial, with advocates for antidepressants insisting that the drugs prevent more suicides than they cause, and publishing studies to this effect.
Glen Spielmans, a psychology professor at Metropolitan State University, looked into whether that was the case by closely evaluating antidepressant clinical trial data. He and his colleagues published their findings in 2020, arguing that the warning label was justified, because pharmaceutical companies had actually downplayed suicide risk in their published antidepressant clinical trial results.
He added that both suicide rates and antidepressant prescriptions have climbed for teens and young adults in recent years, but cautioned against reading too much into these two developments.
“There are so many things you don’t know based upon those two variables that I think it’s really tricky to try to link them,” he said.
Rising depression rates as well as social stressors could explain these numbers because they “would cause both more people to seek antidepressants and also more people to die by suicide”.
The analysis of CDC overdose data found that suicides involving antidepressants increased 2% each year from 1999 to 2015, and have since levelled off, although the authors also say suicides are frequently misclassified as unintentional overdoses.
Spielmans is adamant that doctors should be more mindful when they prescribe antidepressants. They could help mitigate risks by checking in with patients more frequently, although he admitted this might not be practical in an overloaded healthcare system.
Doctors should also be up-front with patients about the possibility antidepressants could lead to suicidal thoughts, as patients are at the highest risk of becoming suicidal when they have just started the medication; when they increase their dosage; or when they go off of it.
“If I were a patient taking a medication and I suddenly felt worse, I’d want to know if it were possible that the medication was making me worse, as opposed to my condition.”
Study details
Trends in Drug Overdose Deaths by Intent and Drug Categories, United States, 1999‒2022
Anallely Nguyen, Jing Wang, Deborah Stone et al.
Published in the American Journal of Public Health on 4 September 2024
Objectives
To examine trends in overdose deaths by intent and drug category to better understand the recent decrease in overdose suicides amid the overdose epidemic.
Methods
We examined trends in rates of overdose deaths by intent (unintentional, suicide, or undetermined) across 9 drug categories from 1999 to 2022 using US National Vital Statistics System mortality data.
Results
Unintentional overdoses involving synthetic opioids, polydrug toxicity involving synthetic opioids, psychostimulants, and cocaine increased exponentially with annual percentage changes ranging from 15.0% to 104.9% during 2010 to 2022. The death rates also increased for suicides involving these drugs, especially for psychostimulants (annual percentage change = 12.9% for 2010–2022; P < .001). However, these drugs accounted for relatively small percentages of overdose suicides. The leading drug categories among suicides were antidepressants, prescription opioids, and benzodiazepines, though these deaths have decreased or levelled off in recent years.
Conclusions
Different drugs commonly involved in suicides and unintentional overdoses may contribute to their divergent trends.
Public Health Implications
Amid the overdose epidemic, safe storage of medications remains a crucial strategy to prevent overdose suicides. The large increases in suicides involving psychostimulants warrant monitoring.
See more from MedicalBrief archives:
Self-harm risk high immediately after starting antidepressants – US analysis
Antidepressant withdrawal symptoms common – meta-analysis
UK lawmakers’ research finds antidepressant withdrawal symptoms severe