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This randomized clinical trial assesses the effectiveness of accelerated intermittent theta-burst stimulation for depressive symptom reduction in patients with treatment-refractory bipolar depression. Key Points: Question: Is accelerated intermittent theta-burst stimulation (aiTBS) clinically effective for treatment-refractory bipolar depression? Findings: In this randomized clinical trial of 24 patients with treatment-resistant bipolar disorder, aiTBS-treated participants had significantly lower depression scores after treatment than did those in the sham group. Meaning: The findings suggest that aiTBS in carefully selected patients offers a new treatment option for this difficult-to-treat illness. Importance: Bipolar disorder (BD) is chronic and disabling, with depression accounting for the majority of time with illness. Recent research demonstrated a transformative advance in the clinical efficacy of transcranial magnetic stimulation for treatment-resistant major depressive disorder (MDD) using an accelerated schedule of intermittent theta-burst stimulation (aiTBS), but the effectiveness of this treatment for treatment-refractory BD is unknown. Objective: To evaluate the effectiveness of aiTBS for treatment-refractory BD. Design, Setting, and Participants: This randomized clinical trial, conducted from March 2022 to February 2024, included individuals with treatment-resistant BD with moderate to severe depressive episodes referred from the Penn Bipolar outpatient clinic. Included patients had 2 or more prior failed antidepressant trials by Antidepressant Treatment History Form criteria and no other primary psychiatric diagnosis, were receiving a mood stabilizer for 4 or more weeks, and had a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or higher. Intervention: Prior to treatment, resting-state functional magnetic resonance imaging was used to compute personalized left dorsolateral prefrontal cortex target by connectivity to subgenual anterior cingulate cortex. Patients were randomized 1:1 to 10 sessions per day of imaging-guided active or sham aiTBS for 5 days with 1 session per hour at 90% resting motor threshold for 90 000 pulses total. Main Outcome and Measures: The main outcome was repeated MADRS scores before and after treatment. Results: A total of 24 participants (12 [50%] female; 12 [50%] male; mean [SD] age, 43.3 [16.9] years) were randomized to active (n = 12) or sham (n = 12) aiTBS. All participants completed treatment and 1-month follow-up. MADRS scores were significantly lower in the active group (mean [SD], 30.4 [4.8] at baseline; 10.5 [6.7] after treatment) than in the sham group (28.0 [5.4] at baseline; 25.3 [6.7] after treatment) at treatment end (estimated difference, –14.75; 95% CI, –19.73 to –9.77; P <.001; Cohen d, –2.19). Conclusion and Relevance: In this randomized clinical trial, aiTBS was more effective than sham stimulation for depressive symptom reduction in patients with treatment-resistant BD. Further trials are needed to determine aiTBS durability and to compare with other treatments. Trial Registration: ClinicalTrials.gov Identifier: NCT05228457 [ABSTRACT FROM AUTHOR]

Existing methods for estimation of dynamic treatment regimes are mostly limited to intention-to-treat analyses—which estimate the effect of randomization to a particular treatment regime without considering the compliance behavior of patients. In this article, we propose a novel nonparametric Bayesian Q-learning approach to construct optimal sequential treatment regimes that adjust for partial compliance. We consider the popular potential compliance framework, where some potential compliances are latent and need to be imputed. The key challenge is learning the joint distribution of the potential compliances, which we accomplish using a Dirichlet process mixture model. Our approach provides two kinds of treatment regimes: (1) conditional regimes that depend on the potential compliance values; and (2) marginal regimes where the potential compliances are marginalized. Extensive simulation studies highlight the usefulness of our method compared to intention-to-treat analyses. We apply our method to the Adaptive Treatment for Alcohol and Cocaine Dependence (ENGAGE) study, where the goal is to construct optimal treatment regimes to engage patients in therapy. [ABSTRACT FROM AUTHOR]

Background: Excessive consumption of opioids is associated with impaired metabolic function including increased body mass index (BMI). Opioid antagonist naltrexone (NTX) is an effective treatment for opioid use disorder (OUD) that has the potential to mitigate such metabolic disturbances. Understanding the relationship between treatment adherence and BMI in NTX-treated OUD patients may provide valuable insights into optimizing clinical outcomes. Methods: Patients with opioid dependence were offered up to three monthly injections of extended-release (XR) NTX. Treatment completers (n = 41) were defined as those who had received all three XR-NTX injections, and noncompleters (n = 20) as those missing at least one injection. Logistic regression was performed to examine the association between pre-treatment BMI and treatment completion. Results: BMI was positively associated with treatment completion. This association remained significant after adjusting for potentially confounding variables. Conclusion: Our findings suggest that baseline BMI may serve as a potential predictor of XR-NTX treatment adherence in patients with OUD and could help healthcare providers and policy makers alike in developing strategies to improve retention and tailor interventions for specific patient subgroups. [ABSTRACT FROM AUTHOR]

Objective: The effects of cognitive-behavioral relapse prevention (RP), contingency management (CM), and their combination (CM + RP) were evaluated in a randomized trial with 100 cocaine-dependent patients (58% female, 89% African American) who were engaged in treatment for at least 2 weeks and had an average of 44 days of abstinence at baseline. Method: The participants were from intensive outpatient programs, which provide 10 hr per week of group counseling. The CM protocol provided gift certificates (maximum value $1,150; mean received = $740) for cocaine-free urines over 12 weeks on an escalating reinforcement schedule, and weekly individual RP sessions were offered for up to 20 weeks. Average number of RP sessions attended was 3 in RP and 13 in CM + RP. Results: Generalizing estimation equation analyses over 18 months postrandomization showed significant effects for CM (but not RP) on urine toxicology and self-reported cocaine use (p = 0.05), with no significant CM x RP interactions. Secondary analyses indicated CM + RP produced better cocaine urine toxicology outcomes at 6 months than treatment as usual, odds ratio [OR] = 3.96 (1.33, 11.80), p less than 0.01, and RP, OR = 4.89 (1.51, 15.86), p less than 0.01, and produced better cocaine urine toxicology outcomes at 9 months than treatment as usual, OR = 4.21 (1.37, 12.88), p less than 0.01, and RP, OR = 4.24 (1.32, 13.65), p less than 0.01. Trends also favored CM + RP over CM at 6 months, OR = 2.93 (0.94, 9.07), p = 0.06, and 9 months, OR = 2.93 (0.94, 9.10), p = 0.06. Differences between the conditions were not significant after 9 months. Conclusions: These results suggest CM can improve outcomes in cocaine-dependent patients in intensive outpatient programs who have achieved initial engagement, particularly when it is combined with RP. (Contains 3 figures and 2 tables.)

A previous randomized trial with 224 alcohol and/or cocaine addicts who had completed an initial phase of treatment indicated that 12 weeks of telephone-based continuing care yielded higher abstinence rates over 24 months than did group counseling continuing care. The current study examined mediators of this treatment effect. Results suggested that self-help involvement during treatment and self-efficacy and commitment to abstinence 3 months after treatment mediated subsequent abstinence outcomes. These analyses controlled for substance use prior to the assessment of mediators. Conversely, there was no evidence that self-help beliefs or social support mediated the treatment effect. These results are consistent with a model in which treatment effects are first accounted for by changes in behavior, followed by changes in self-efficacy and in commitment to abstinence.

This study of continuing care for substance dependent patients compared a telephone-based monitoring and brief counseling intervention (TEL) with 2 face-to-face interventions, relapse prevention (RP) and standard 12-step group counseling (STND). The participants were graduates of intensive outpatient programs who had current dependence on alcohol and/or cocaine. Self-report, collateral, and biological measures of alcohol and cocaine use were obtained over a 12-month follow-up. The treatment groups did not differ on abstinence-related outcomes in the complete sample (N = 359) or on cocaine use outcomes in participants with cocaine dependence (n = 268). However, in participants with alcohol dependence only (n = 91), TEL produced better alcohol use outcomes than STND on all measures examined and better outcomes than RP on some of the measures.