Evaluating a Longitudinal Mediation Model of Perceived Stress, Depressive Symptoms, and Substance Use Treatment Outcomes

The allostatic model of addiction suggests that negative affect, such as depressive symptoms, mediates the effect of stress on outcomes among individuals with substance use disorders. However, few longitudinal treatment studies have demonstrated this effect. We analyzed data from a 12-week randomized trial of galantamine and/or computerized cognitive-behavioral therapy (CBT4CBT) for individuals (N = 120) with cocaine use disorder in methadone treatment for opioid use disorder. We evaluated baseline perceived stress as a predictor of end-of-treatment (EOT) substance use outcomes, and EOT perceived stress as a predictor of month 6 posttreatment outcomes. We conducted mediation models with intervening depressive symptoms as a mediator. We also explored whether CBT4CBT moderated the effects of perceived stress. Baseline perceived stress did not predict EOT outcomes (i.e., total effect). However, in mediation models, we found indirect effects of baseline perceived stress on EOT cocaine and illicit opioid use, via midtreatment depressive symptoms. EOT perceived stress had significant total effects on month 6 cocaine and illicit opioid use, and an indirect effect on month 6 illicit opioid use (but not cocaine use), via month 3 depressive symptoms. Alternative models with depressive symptoms as the predictor and perceived stress as a mediator revealed no indirect effects. The addition of CBT4CBT to standard methadone treatment did not moderate total or indirect effects of perceived stress on substance use. Depressive symptoms may play a mediating role in the prospective indirect effect of perceived stress on substance use outcomes, particularly illicit opioid use. Further research is needed on therapies targeting stress.