1. Initiating a prescription opioid is associated with a more than doubled risk of suicidal behavior in adolescents and young adults.
2. However, when adjusting for confounding variables such as the presence of pain, this increased risk of suicidal behavior is significantly reduced to only 19%.
Evidence Rating Level: 2 (Good)
Study Rundown: Adolescent suicide by opioid overdose has been increasing in recent years. Despite this fact, the association of suicide with prescribed opioid initiation is not well-studied. This retrospective cohort study sought to investigate how initiation of a prescription opioid contributes to suicide risk in adolescents and young adults by comparing data from prescription opioid-initiators to non-initiators. This study also attempted to account for pain as an independent suicide risk factor by comparing prescription opioid-initiators to prescription non-steroidal anti-inflammatory drug (NSAID)-initiators. While researchers found that prescription opioid-initiators were at a more than doubled risk of suicidal behavior when compared to non-initiators, this risk was substantially decreased when compared with NSAID-initiators. Ultimately, opioid-initiators had a 19% increased risk of suicidal behavior compared to NSAID-initiators, suggesting that pain is a greater driver of suicidal behavior than prescription opioid-initiation. These results should be considered when health care providers weigh the potential benefits and harms of prescribing opioids to youths and young adults. This study is strengthened by its large, nation-wide cohort and robust sensitivity analyses. Nevertheless, the retrospective design makes it impossible to distinguish between correlation and causation. Furthermore, data gathered from diagnostic coding can be unreliable and may not represent the true incidence of suicidal behavior, including suicidal behavior that was never identified by a health care provider.
In-Depth [retrospective cohort]: This study gathered data on a nationwide Swedish birth cohort of youths and young adults aged 9-29. Data were gathered from multiple national population and health registers under Statistics Sweden. The birth cohort included nearly 2 million people without prior opioid prescriptions, of which 201,433 initiated a new opioid prescription during the study period of 2007-2013. The primary outcome of this study was reported suicidal behavior, determined using International Classification of Diseases, Tenth Revision (ICD-10) codes and recorded causes of death. Researchers found that prescription opioid-initiators had a nearly doubled risk of suicidal behavior when compared to non-initiators (HR 2.64, 95% CI 2.47-2.81). However, researchers also used an active comparator design to adjust for pain as a confounder, comparing prescriptions opioid-initiators with prescription NSAID-initiators. With this comparison, it was found that the increased risk of suicidal behavior was still significant but much smaller in opioid-initiators compared to NSAID-initiators (HR 1.19, 95% CI 2.1-2.4). These results were supported by numerous sensitivity analyses including adjustments for depression, cancer pain, age, and more.
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