Cessation of opioid agonist therapy (OAT) significantly increases the risk of self-harm and death by suicide in the first month after stopping the treatment in new findings that highlight the need for "advanced safety planning" during this critical time.
Investigators found that 4 weeks after stopping OAT, the risk of death by suicide was almost five times higher and the risk of hospital admission for self-harm was almost three times higher during this period compared to the 4 weeks after initiation of OAT to treatment end.
Dr Prianka Padmanathan
These results highlight the importance of a "transition" period when stopping OAT and highlight the need for better supports for patients coming off this treatment, study investigator Prianka Padmanathan, MD, PhD candidate, Population Health Sciences, University of Bristol, United Kingdom, told Medscape Medical News.
She noted the study supports previous findings that OAT "has an important role" in suicide prevention.
"Suicide and self-harm risk is greatly increased during treatment cessation, and advanced safety planning and additional psychosocial support during this time may be required," Padmanathan said.
The findings were published online December 15 in The Lancet Psychiatry.
Suicide, Self-Harm Risk
Previous research shows an increased risk for overdose deaths and death in general during the first few weeks of starting and stopping treatment for opioid dependence.
"We wanted to see if the risk of dying by suicide was also elevated during these times," said Padmanathan. As suicides are relatively rare, the researchers also looked at self-harm, "which is an important risk factor for suicide."
The investigators used linked healthcare databases to gather information on mortality and hospital admissions among primary care patients in England prescribed OAT, particularly buprenorphine or methadone.
"We tried to exclude people prescribed these drugs for pain and focused specifically on their prescription for opioid dependence," Padmanathan said.
They estimated rates and adjusted risk ratios (aRRs) of hospital admissions for nonfatal self-harm and completed suicide during treatment initiation, maintenance, and cessation.
The study included 8070 patients (69.3% men; mean baseline age, 33.3 years) who received OAT at least once from January 1998 through November 2018. The median treatment time was 84 days. Most of the participants lived in the most deprived neighborhoods and were White.
There were 807 hospital admissions for self-harm (1.99 per 100 person-years) and 46 suicides (0.11 per 100 person-years).
The investigators examined age, sex, socioeconomic status, number of previous OAT treatment episodes, previous self-harm, previous mental illness, and major chronic illness scores as potential confounders.
Need for Psychosocial Care
Results showed the risk for self-harm was significantly increased while off OAT (aRR, 1.5; 95% CI, 1.21 – 1.88).
The overall age- and sex-standardized mortality ratio for suicide was 7.5 times higher (95% CI, 5.5 – 10) in the study cohort compared to the general population in England between 1998 and 2017.
There was insufficient evidence to show the risk for suicide was higher off, vs on, treatment, but this may be because suicides are relatively rare, Padmanathan noted.
"The sample may have been too small to enable a difference to be detected. In contrast, self-harm is more common, so there was power to detect a difference there," she said.
Risk for self-harm was more than double in the first 4 weeks after stopping OAT vs stable periods on treatment (aRR, 2.60; 95% CI, 1.83 – 3.7). Risk for suicide more than quadrupled during this period (aRR, 4.68; 95% CI, 1.63 – 13.42).
These new results suggest additional interventions may be in order, Padmanathan noted.
"We already knew that extra care ― for example, providing naloxone when coming off OAT ― was important to prevent overdoses. But this study suggests providing psychosocial care and other extra care may also be important to prevent suicides," she said.
There was no statistical evidence of difference between buprenorphine and methadone in terms of self-harm and suicide risks. However, this may be because the sample was not large enough to detect a difference, said Padmanathan.
Although there are currently no guidelines to indicate an ideal OAT period, previous study results have suggested extending treatment to 2 years may be beneficial, perhaps reducing self-harm and, therefore, suicides, she noted.
"We think most of these adverse outcomes likely occur during short treatment episodes with an unplanned ending. Extending OAT sufficiently to enable a planned ending might help to reduce these risks," she added.
"A Window of Vulnerability"
Authors of an accompanying editorial note the study "adds weight" to the evidence that OAT is a "lifesaving" treatment.
"It's critical to recognize that transitions in and out of care are vulnerable periods" when it comes to suicide, the co-author of the editorial, Paul S. Nestadt, Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, told Medscape Medical News.
Official suicide statistics may not reflect the entire story, as many deaths that occur because of overdose after treatment cessation are not counted as suicides, he said. "It can be difficult for medical examiners to determine if an overdose was intentional or not," Nestadt added.
After treatment has been established, physicians "would be wise to delay treatment cessation" until the patient is in a stable condition and can be closely followed by mental health professionals, the editorialists note.
"We must consider the month following OAT cessation to be a window of vulnerability, not just for relapse but also for suicide," they write.
The finding that patients prescribed OAT have such a high rate of suicide compared with the general population is "troubling" and "highlights the importance of interventions which address both opioid use and suicide risk," they add.
The editorialists point out the median treatment period of 84 days is less than what is generally recommended, raising the question of whether longer treatment might lower suicide risk after treatment discontinuation.
They also emphasized the need for further study to test potential suicide prevention interventions in the period after treatment cessation.
Nestadt added the new findings are "quite generalizable outside of the UK" and referred to similar studies carried out in Australia and elsewhere.
The study was funded by the Medical Research Council. Padmanathan was a co-applicant on an a grant awarded to University of Bristol by Bristol and Weston Hospital Charity focusing on suicide prevention for patient presenting to the Emergency Department with self-harm and harmful substance use. Nestadt has reported no relevant financial relationships.
Lancet Psychiatry. Published online Dec 15, 2021. Abstract, Editorial
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