When two drugs are not better than one: Treating mood symptoms in patients with chronic opioid use.

[First paragraph] Drug overdose fatalities in the United States have reached an all-time high. Deplorably, many other countries are following suit. The Centers for Disease Control and Prevention reports that, in 2017, opioids were involved in 47,600 overdose deaths (CDC, 2018), a number which dwarfs the number of car crash fatalities in the same year. Regrettably, the ‘Inexorable March to Death and Addiction’ (Theisen and Davies, 2019) is fueled, to a large part, by an invidious trend of medical overprescribing and misprescribing, which disproportionately affects patients with mental health disorders (Seal et al., 2012). Moreover, accruing evidence suggests that opioid use may directly precipitate depressive symptoms. For example, a large retrospective cohort study collating data from three independent healthcare systems including the Veterans Health Administration demonstrated that duration of opioid use is associated with the new onset of depression (Scherrer et al., 2016a). The risk of developing treatment-resistant depression was also found to grow with duration of opioid exposure (Scherrer et al., 2016b).