Background and Objectives Buprenorphine's high‐binding affinity as a partial µ‐opioid agonist displaces preexisting full agonists causing precipitated withdrawal, which requires most individuals starting buprenorphine to endure moderate withdrawal prior to induction to avoid precipitated withdrawal. A novel approach called microinduction has emerged to remove this prerequisite. Our aim is to review the literature on these alternative approaches. Methods Using keywords including buprenorphine, buprenorphine/naloxone, transdermal buprenorphine, suboxone, microinduction, microdosing, rapid induction, buprenorphine‐dosing protocol, the authors searched PubMed/Medline, EMBASE, PsycINFO, PsychARTICLES, and Scopus databases from the date of inception through April 30, 2020, which yielded 1726 results, which, in turn, after manual exclusion for irrelevant content and publication in languages other than English, generated a total of 18 papers. Results On the basis of 18 papers included in this review, 63 patients were successfully transitioned to buprenorphine using different microdosing techniques, primarily in the inpatient setting. From the available data, patients were transitioned from a variety of opioids over a range of dosing without significant withdrawal, and initial doses ranged most frequently from 0.2 to 0.5 mg. While the timeframe for the various schedules ranged from 3 to 112 days, most transitioned over a period of 4 to 8 days, and most participants completed the cross titration at 8 to 16 mg. Discussion and Conclusions The growing literature demonstrates some initial promise for alternative induction models, specifically targeting patients averse to withdrawal, patients prescribed opioids for chronic pain, patients on high‐dose methadone, and patients using illicit or pharmaceutical fentanyl. Scientific Significance This manuscript provides a review of the existing literature to help clinicians better understand the approaches to microdosing of buprenorphine in various clinical settings and populations. (Am J Addict 2020;00:00–00)

Background Many clinical trials use composite endpoints to reduce sample size, but the relative importance of each individual endpoint within the composite may differ between patients and researchers. Methods and Results We asked 785 cardiovascular patients and 164 clinical trial authors to assign 25 “spending weights” across 5 common adverse events comprising composite endpoints in cardiovascular trials: death, myocardial infarction (MI), stroke, coronary revascularization, and hospitalization for angina. We then calculated endpoint ratios (“ratios”) for each participant’s ratings of each nonfatal endpoint relative to death. Whereas patients assigned an average weight of 5 to death, equal or greater weight was assigned to MI (mean ratio 1.12) and stroke (ratio 1.08). In contrast, clinical trialists were much more concerned about death (average weight of 8) than MI (ratio 0.63) or stroke (ratio 0.53). Both patients and trialists considered revascularization (ratios 0.48 and 0.20, respectively) and hospitalization (ratios 0.28 and 0.13, respectively) as substantially less severe than death. Differences between patient and trialist endpoint weights persisted after adjustment for demographic and clinical characteristics (p<0.001 for all comparisons). Conclusions Neither patients nor clinical trialists weigh individual components of a composite endpoint equally. While trialists are most concerned about avoiding death, patients place equal or greater importance on reducing MI or stroke. Both groups considered revascularization and hospitalization as substantially less severe. These findings suggest that equal weights in a composite clinical endpoint do not accurately reflect the preferences of either patients or trialists.

Four transcranial magnetic stimulation (TMS) devices are currently approved for use in treatment-resistant depression. The authors present the first data-driven study examining the patient- and technician-experience using three of these distinct devices. A retrospective survey design with both patient and technician arms was utilized. The study population included patients who received TMS for treatment-resistant depression at the Berenson Allen Center for Noninvasive Brain Stimulation for the first time between 2013 and 2016 and technicians who worked in the program from 2009 to 2017. Statistical analysis included t tests and analyses of variance to assess differences between and across the multiple groups, respectively. Patients treated with the NeuroStar device reported greater confidence that the treatment was being performed correctly compared with those treated with the Magstim device. Conversely, with regard to tolerability, patients treated with the Magstim device reported less pain in the last week and less pain on average compared with those treated with the NeuroStar device. On average, technicians reported feeling that both the Magstim and NeuroStar devices were significantly easier to use than the Brainsway Deep TMS H-Coil device. Additionally, they found the former two devices to be more reliable and better tolerated. Furthermore, the technicians reported greater confidence in the Magstim and NeuroStar devices compared with the Brainsway Deep TMS H-Coil device and indicated that they would be more likely to recommend the two former devices to other treatment centers.

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