Abstract

Treatment guidelines discourage long-term opioid treatment for patients with chronic pain and major depression, but this treatment occurs commonly, producing higher daily doses, longer duration, and more adverse events. Review of prospective cohort, retrospective cohort, and other observational studies of the relation between depression and opioid use, abuse, and addiction. Depressed patients initiate opioid therapy slightly more often than nondepressed patients, but are twice as likely to transition to long-term use. This adverse selection of high-risk patients with depression into long-term high-dose opioid therapy seems to be a process of self-selection. Opioids may be used by patients with chronic pain and depression to compensate for a reduced endogenous opioid response to stressors. Depressed patients seem to continue opioid use at lower pain intensity levels and higher levels of physical function than do nondepressed patients. In studies that carefully control for confounding by indication, it has been shown that long-term opioid therapy increases the risk of incident, recurrent, and treatment-resistant depression. Depressed patients may tend to overuse opioids because they use them to treat insomnia and stress. Depression also seems to increase the risk of abuse or nonmedical use of prescription opioids among adults and adolescents. This increased rate of nonmedical opioid use may be the path through which depression increases the risk of opioid use disorder among patients with chronic pain. It is not possible to understand long-term opioid therapy for chronic pain without understanding the close and multifaceted relationship of this therapy with depression.

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