Can buprenorphine reduce suicide mortality?

Substance use disorders (SUDs) are highly prevalent worldwide and a significant medical and social problem around the world.1–4 According to the UN Office on Drugs and Crime, globally, about 275 million individuals (or 5.5% of the global population aged 15–64 years) used drugs at least once in 2019. Among them, about 62 million people used opioids. Worldwide, about 36.3 million people had substance use disorders in 2019. SUDs are among the leading causes of morbidity and mortality globally.1–4 SUDs are associated with various medical illnesses including infectious diseases, chronic pulmonary, cardiovascular and gastrointestinal disorders. SUDs are frequently comorbid with other psychiatric disorders including depression, anxiety, and posttraumatic stress disorder. Regretfully, most individuals with SUDs never receive treatment for SUDs. SUDs are a significant risk factor for suicidal behavior. Individuals with SUDs have a 10–14 times larger risk of death by suicide compared with the general population. One investigation found that opioids were present in 20% of suicide deaths, marijuana in 10.2%, cocaine in 4.6%, and amphetamines in 3.4%. Many drug overdoses may be unrecognized suicides. Drug-overdose deaths are often categorized as “undetermined” if there is no known history of depressive disorder or a suicide note. The United States has seen a significant increase in drug overdose deaths and suicides in the past two decades. Drug overdose deaths exceeded an annual rate of 100,000 for the first time in 2021. According to the National Center for Health Statistics of the U.S. Centers for Disease Control and Prevention report, there were 107,622 drug overdose deaths in the United States during 2021, an increase of nearly 15% from the 93,655 deaths in 2020. Over 75% of overdoses were related to the use of opioids, frequently fentanyl. The rate of drug poisoning deaths continues to increase in other countries. For example, the rate of drug poisoning deaths in England and Wales was 81.1% higher in 2021 than it was in 2012. Medications for opioid use disorder (OUD) are an effective treatment for patients with OUD and, frequently, need to be combined with psychotherapy. Three current medications for the management of OUD approved by the U.S. Food and Drug Administration include methadone (an opioid agonist), buprenorphine (a partial opioid agonist), and naltrexone (an opioid antagonist). An important and timely study comparing mortality rates for buprenorphine and methadone treatments among a large sample of U.S. Department of Veterans Affairs (VA) patients with OUD residing in the 50 United States and Washington, DC, is published in this issue of the journal. The authors obtained data from VA databases as well as linked Medicaid claims for VA patients who received methadone and buprenorphine from 2010 through 2019 and measured all-cause mortality, overdose mortality, and suicide mortality among these patients. The authors found that buprenorphine is associated with an approximately 20% reduction in risk adjusted all-cause mortality and 40% reduction in suicides compared with methadone. No differences were observed in overdose mortality. The authors proposed that the benefit of buprenorphine over methadone in the United States is mediated by greater patient retention in treatment. The authors also observed that there were substantial and sustained regional differences in prescribing buprenorphine versus methadone. This may indicate that generally recognized and accepted guidelines for prescribing buprenorphine and methadone are needed. Earlier, the same research group examined suicide mortality, external causes of mortality, and all-cause mortality in a large sample in the 5 years following initiation of buprenorphine, methadone, or naltrexone. When comparing effects of these medications on mortality risk, only buprenorphine had a significant effect on reducing suicide mortality and external causes of mortality in models adjusted for demographic characteristics, comorbidities, and health care utilization. Buprenorphine was associated with a decrease of suicide risk of more than 65%. Other studies also suggest that the use of buprenorphine reduces suicidal and self-injurious behavior. For example, another retrospective cohort study of U.S. Veterans receiving buprenorphine in 2008–2017 across any VA facility showed that Veterans who were not receiving buprenorphine were 4.3 times more likely to die by suicide/overdose than those receiving buprenorphine on any given day. Also, the risk of suicide/overdose was highest 8–14 days from buprenorphine discontinuation in comparison to currently receiving buprenorphine pharmacotherapy. Received: 28 September 2022 Revised: 9 October 2022 Accepted: 10 October 2022