There is a substantial co-occurrence between substance use disorders (SUDs) and bipolar disorder. This comorbidity pattern is associated with a host of negative outcomes. The co-occurrence of SUDs and bipolar disorder is related to even poorer adherence rates, and nonadherence is a consistent predictor of negative outcomes. The transition from psychiatric hospitalization to outpatient care is a time of heightened risk in this population for nonadherence, substance relapse, and suicidality. To date, there is very little research on effective and feasible behavioral interventions designed to improve treatment adherence and engagement in this high-risk, comorbid population at the critical period following hospital discharge. Supported by a previous treatment development grant from NIDA, we developed a novel psychosocial intervention as an adjunct to treatment as usual, designed to reduce substance abuse, nonadherence, mood symptoms, and other clinical outcomes among high-risk patients with co-occurring SUDs and bipolar disorder. This intervention, called the “Integrated Treatment Adherence Program” (ITAP), is an innovative approach that combines brief in-person engagement sessions with follow-up phone sessions and family/significant other involvement, as an adjunct to treatment as usual over 6 months post-discharge. Pilot data on the ITAP intervention have been quite promising, showing faster and larger improvements in outcomes such as drug days using, mood symptoms, and adherence compared to treatment as usual. However, further testing is needed to confirm the efficacy and feasibility of delivering ITAP in typical clinical settings. The present project is designed to meet the objectives of Stage II treatment development research (PA-18-055). We propose to conduct a fully-powered clinical trial evaluating ITAP by randomly assigning 160 patients with comorbid SUDs and bipolar disorder, initially recruited during a psychiatric hospitalization and followed after discharge, to either the ITAP intervention or a Safety Assessment and Follow-up Evaluation (SAFE) comparison condition, both delivered as adjuncts to community treatment as usual. We will train master's level hospital therapists to deliver ITAP/SAFE and measure therapist fidelity to the intervention. We will conduct blind follow-up assessments at 3 (mid-treatment), 6 (post-treatment), and 9 month follow-ups. We hypothesize that, compared to those receiving SAFE, patients assigned to ITAP will have fewer days using drugs, lower mood symptoms and suicidality, and higher rates of adherence to psychiatric and substance abuse medications (based on electronic monitoring) at post-treatment maintained through follow-up. We also will test whether the proposed mechanisms of ITAP (greater treatment adherence, values-action consistency) mediate substance use and other clinical outcomes, as well as test potential moderators of outcomes (substance type, gender, baseline mood episode). When completed, this st...