From the Journals

Antidepressants may curb opioid overdose



Patients with a history of depression who are also being treated with opioid analgesics have a lower risk for overdose and self-harm after taking antidepressants, new research suggests.

Investigators analyzed insurance claims for more than 200,000 adults with a history of depression. Of these, 8,200 experienced adverse events (AEs) during the year after initiation of opioid therapy.

However, the risk for an AE such as overdose and other forms of self-harm was reduced among patients who had been treated with antidepressants for at least 6 weeks.

The take-home message is that clinicians and health systems need to be more aware that individuals in pain are more likely to be depressed and at higher risk for AEs – so the depression should be treated “more liberally,” corresponding author Bradley Stein, MD, PhD, a practicing psychiatrist in Pittsburgh and director of the Rand Corporation Opioid Policy Center, told this news organization.

“If you are treating someone with pain, particularly chronic pain, it’s critically important to better assess their depression and not to attribute depressive symptoms only to pain,” Dr. Stein said.

The findings were published online in Psychiatric Services.

Promising approach?

Opioid treatment for pain “complicates the interactions among pain, depression, and self-harm,” the investigators write. Individuals with depression receiving long-term opioid therapy are two to three times more likely to misuse opioids, compared with individuals who do not have depression.

Although comorbid depression “substantially increases overdose and suicide risk, it remains underdiagnosed and undertreated among individuals with chronic pain,” the researchers note. They add that increasing access to depression treatment may be a “potentially promising approach to preventing overdoses and suicide” in these patients.

“We know that individuals using opioids who have a history of depression are more likely to have negative outcomes, such as overdoses and self-harm events,” Dr. Stein said. “We wanted to see whether antidepressants, which would treat depression in these individuals, would help with that.”

The researchers assessed a database of commercial insurance claims of adults with a history of depression who received opioids between 2007 and 2017 (n = 283,374). The data included 336,599 opioid treatment episodes.

To be included in the study, patients had to have been diagnosed with depression before they filled their first opioid prescription.

The “outcome of interest” was time from the beginning of an opioid episode until an adverse event, such as opioid poisoning, overdose of nonopioid controlled or illicit substances, or self-harm unrelated to overdose.

Participants were followed from the onset of the opioid episode until an AE occurred, loss to follow-up, or week 52, whichever came first.

The “key independent variable” was filling an antidepressant prescription. The patient’s sex and age were considered to be independent variables as well.

Teasing out antidepressant effect

Of participants with a history of depression treatment, 8,203 experienced at least one AE during the 12 months after treatment initiation (n = 47,486 AEs). Approximately half (50.8%) filled an antidepressant prescription at least once during the 12 months after the opioid episode began.

AEs were more likely among men than among women. The highest risk was in patients aged 18-24 years.

After adjusting for age and sex, participants who had received antidepressants had a greater risk for all adverse outcomes during the first 6 weeks of antidepressant treatment. However, those who had received antidepressants for 6 weeks or longer were at reduced risk for all adverse outcomes.

“We took advantage of the fact that, for most people, antidepressants take a while to work and aren’t immediately effective, so we were able to use that difference in our research,” Dr. Stein said.

“We wouldn’t expect to see an immediate effect of antidepressants, so the difference between what we saw immediately after the person had started treatment and the time it took for the antidepressant to be effective enabled us to tease out the effect of the antidepressant,” he added.


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