Background & Introduction: Extended-release naltrexone has the potential to reduce medication adherence barriers (e.g., unstable housing or transportation challenges) that disproportionately affect marginalized populations. Limited research exists on naltrexone's effects on cocaine craving and depression, and the results are mixed. Moreover, no studies have examined longitudinal response patterns of craving-depression trajectories and substance use outcomes. This study used latent class growth analysis (LCGA) to identify distinct trajectories of depression and craving symptoms during naltrexone-based treatment for cocaine use disorder.
Methods: We conducted a secondary analysis of CTN-0048, a randomized controlled trial (n=296) at 11 treatment sites across nine states. Participants were treatment seeking adults aged 18-65 who had a DSM-IV diagnosis of cocaine dependence with past-year opioid use disorder or past year opioid use with a history of opioid dependence. All participants received extended-release naltrexone and weekly cognitive behavioral therapy over 8 weeks, with clinic visits three times weekly. We used LCGA to identify trajectory patterns of depression (Beck Depression Inventory) and cocaine craving (Visual Analog Scale) measured at baseline and weekly across eight weeks of treatment. Model fit was evaluated using Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), Vuong-Lo-Mendell-Rubin test, and entropy values. We then examined latent class differences in demographic characteristics, treatment group assignment, treatment effect (Treatment Effect Assessment-substance use), and cocaine use (urine test).
Results: The majority of the sample was male (78.4%), Non-Hispanic (89.5%), and Black/African American (63.2%). LCGA showed the 4-class model provided optimal fit (AIC=40577.499, BIC=40773.088, entropy=0.944). Class 1 (Persistent High Craving-Low Depression Class; 11%) showed high baseline craving with minimal improvement and stable low depression. Class 2 (Craving-Responsive-Persistent Depression Class; 26%) had moderate baseline symptoms with large craving reductions but limited depression improvement. Class 3 (High Depression-Moderate Craving Class; 8%) exhibited high baseline depression and craving with minimal depression improvement and moderate craving improvement. Class 4 (Low Baseline Symptom Class; 55%) showed the lowest symptoms across both domains with moderate baseline craving and improvement and low depression with limited improvement. Gender, ethnicity, race, and treatment group assignment did not significantly differ by class membership. Age varied by class, wherein Class 2 were older than those in Classes 3 and 4. Classes 1 and 3 had significantly worse treatment outcomes than Classes 2 and 4. Class 1 and Class 3 had the lowest rating of treatment effectiveness at both 1-month and 3-month post-treatment follow-ups. Additionally, Class 1 had the highest number of positive urine tests (m = 14.0, SD = 7.9) and percent positive tests (m = 75.2%, SD = 33.8%) of all classes.
Conclusion & Discussion: Four distinct response profiles emerged during naltrexone treatment, demonstrating that depression and craving trajectories can diverge substantially. Persistent high craving with low depression (Class 1) and sustained high depression with moderate craving (Class 3) associated with poorer treatment responses, including lower perceived treatment effectiveness and higher cocaine use. These findings suggest treatment response is heterogeneous and potentially predictable based on baseline symptom profiles and early treatment indicators of craving/depression. Since sustained high craving or depression are linked to poorer substance use outcomes, treatment protocols should incorporate ongoing symptom monitoring with provision of domain-specific supportive interventions (e.g., craving management techniques, depression-focused therapy) when trajectories signal poor response. The main limitations involved the observational nature of this secondary analysis, which cannot determine whether trajectories represent treatment effects versus natural recovery patterns.
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Disclosure(s):
Audrey Hai, PhD: No financial relationships to disclose
Noel A. Vest, PhD: No financial relationships to disclose
Learning Objectives:
Identify the four distinct depression-craving trajectory profiles during extended-release naltrexone treatment for cocaine use disorder.
Describe the relationship between persistent high craving or depression and poorer substance use outcomes (lower treatment effectiveness and higher cocaine use rates).
Explain why ongoing symptom monitoring with domain-specific supportive interventions when trajectories signal poor response is necessary for patients receiving naltrexone-based treatment for cocaine use disorder.
