Opioid use is often comorbid with major depressive disorder (MDD) and anxiety and stress-related disorders (ASRD). Determining the direction and potentially causative effects of these associations would be valuable to prevention strategies. Mendelian randomization, which uses single nucleotide variants as unconfounded proxies for exposures to estimate their effect on outcomes of interest, was used to determine genetic susceptibility of prescription opioid use, MDD, and ASRD, as well as their bidirectional associations. Summary statistics of publicly available genome-wide association studies were used to calculate the genetic susceptibilities, which were based on data from individuals from predominantly European ancestry. Genetically determined prescription opioid use was associated with an increased risk for MDD (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.06 – 1.22, p < 0.001) and ASRD (OR = 1.24, 95% CI = 1.07 – 1.44, p < 0.001), even after accounting for non-opioid pain medication or comorbid pain conditions, suggesting important neuropsychiatric implications beyond the risk for opioid misuse that should be considered when prescribing opioids. Conversely, genetic liability for MDD, but not ASRD, was associated with increased risk for use of opioid (OR = 1.18, 95% CI = 1.08 – 1.30, p < 0.001; Figure 1) and non-opioid (i.e., anilides, nonsteroidal anti-inflammatory drugs, salicylic acid/derivatives; OR = 1.10, p = 0.002) medications. This finding indicates that genetic liability for MDD may be a causal risk factor for opioid use and that targeting opioid use prevention for patients with MDD may help mitigate the opioid epidemic. Studies assessing dose dependent changes in risk associated with prescription opioids and studies in individuals of non-European ancestry are needed.
Figure. 1 Genetically determined prescription opioid use was associated with increased risk for major depressive disorder (MDD; odds ratio = 1.14, p < 0.001) and anxiety and stress-related disorders (ASRD; odds ratio = 1.24, p < 0.001), even after accounting for non-opioid pain medication or comorbid pain conditions. Genetic liability for MDD, but not ASRD, was associated with increased prescription opioid use risk (odds ratio = 1.18, p < 0.001).
Rosoff DB et al. JAMA Psychiatry 2020;e203554. Abstract