Individuals With Major Depressive Disorder May Have a Genetic Liability Which Increases Risk for Opioid Use

This study addresses the question of whether prescription opioid medications has a potentially causal role in the risk for depression and anxiety disorder.

Researchers from the National Institute on Alcohol Abuse and Alcoholism observed a potential genetic link between major depressive disorder (MDD) and anxiety and stress-related disorders (ASRD) with increased prescription opioid use. These results were published in JAMA Psychiatry.

Data from 3 published genome wide association studies (N=737,473) were combined for this analysis. The relationship between self-reported use of pain medications (opioids, salicylic acid, anilides, nonsteroidal anti-inflammatory drugs [NSAIDs]) among individuals with MDD (n=45,591) and ASRD (n=12,665) was associated with the genetics of the disorders using a 2-sample Mendelian randomization approach.

Risk for opioid use was increased among individuals with MDD (inverse variance weighted odds ratio [IVW OR], 1.14; 95% CI, 1.06-1.22; P <.001) and ARSW (IVW OR, 1.24; 95% CI, 1.07-1.44; P =.004) in a single-variable model.

This increased risk was replicated in a multi-variable model (MDD: IVW OR, 1.14; 95% CI, 1.04-1.25; P =.005; ARSD: IVW OR, 1.30; 95% CI, 1.08-1.56; P =.006).

Controlling for back-specific pain, the increased risk for MDD (IVW OR, 1.12; 95% CI, 1.05-1.21; P =.001) and ARSW (IVW OR, 1.26; 95% CI, 1.09-1.45; P =.002) remained significant.

Using a bidirectional single-variable approach, among individuals with MDD, based on 92 single nucleotide variants (SNVs), risk was increased for opioid (IVW OR, 1.18; 95% CI, 1.08-1.30; P <.001), salicylic acid (IVW OR, 1.10; 95% CI, 1.03-1.17; P =.002), anilides (IVW OR, 1.20; 95% CI, 1.00-1.28; P <.001), and NSAIDs (IVW OR, 1.15; 95% CI, 1.09-1.22; P <.001) use.

With the same bidirectional approach, among individuals with ARSW and based on 17 SNVs, no increased risk was identified for use of opioids (IVW OR, 1.04; 95% CI, 0.97-1.12; P =.29), salicylic acid (IVW OR, 1.05; 95% CI, 0.99-1.11; P =.11), anilides (IVW OR, 1.02; 95% CI, 0.97-1.06; P =.43), or NSAIDs (IVW OR, 1.01; 95% CI, 0.96-1.06; P =.80).

These results may have been limited by the study population, which was overwhelmingly of European ancestry, and therefore may not be generalizable for individuals with other ancestries.

These data suggested there may be important clinical considerations for physicians when prescribing opioids to patients with MDD or ASRD, as these patients may be at a greater risk for increased opioid use.


Rosoff DB, Smith, GD, Lohoff FW. Prescription opioid use and risk for major depressive disorder and anxiety and stress-related disorders a multivariable mendelian randomization analysis. JAMA Psychiatry. Published online November 11, 2020.  doi:10.1001/jamapsychiatry.2020.3554

This article originally appeared on Psychiatry Advisor