Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial.

OBJECTIVE: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of ∼90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression. METHODS: Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 4 weeks after treatment. RESULTS: At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group. CONCLUSIONS: SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.

Oxytocin-enhanced group therapy for methamphetamine use disorder: Randomized controlled trial.

BACKGROUND: Methamphetamine (METH) use is a public health crisis that disproportionately affects men who have sex with men (MSM). There are currently no FDA-approved pharmacological interventions to treat methamphetamine use disorder (MUD). MUD is associated with social impairments and extremely high treatment attrition rates. Administration of oxytocin, a neuropeptide involved in social attachment, may be a novel approach to addressing these issues. Moreover, oxytocin administration has shown promise for reducing METH-related addictive behavior in animal models, but has not yet been investigated in clinical trials for MUD. Last, oxytocin is known to modulate stress responsivity via regulation of the autonomic nervous system, which is dysregulated in METH users. We hypothesize that oxytocin, in combination with group psychotherapy, will increase treatment engagement, reduce addiction behavior, and mitigate stress hyperreactivity. METHODS: This is a randomized, double blind trial of oxytocin 40-IU (n = 24) or placebo (n = 24) administered intranasally prior to each of six weekly motivational interviewing group therapy (MIGT) sessions for MUD in MSM. PRIMARY OUTCOME: (a) session attendance. SECONDARY OUTCOMES: (b) group cohesion, (c) anxiety, (d) METH craving, (e) METH use, and (f) in-session cardiac physiology. RESULTS: Participants receiving oxytocin had significantly higher group therapy attendance than those receiving placebo, OR 3.26, 95% CI [1.27-8.41], p = .014. There was a small effect of oxytocin on group cohension, but not anxiety or craving. METH use did not change over the six-week MIGT course in either treatment arm. Participants receiving oxytocin had lower average heart rates during MIGT sessions and higher heart rate variability. There were positive main effects of MIGT over Time regardless of study drug. CONCLUSIONS: This evidence, and the lack of any serious adverse events, suggests that oxytocin may safely increase treatment attendance. One possible mechanism by which it may do so is its modulation of the autonomic nervous system. Further investigation is warranted.

An inverse relationship between perceived social support and substance use frequency in socially stigmatized populations.

INTRODUCTION: Social isolation and alcohol and substance use disorders (ASUD) have been identified as global health risks. Social support is protective against developing ASUD and is associated with beneficial addiction treatment outcomes. Socially stigmatized populations are at higher risk of both social isolation and ASUD, and the link between social support and substance use in these populations has been less researched than in general substance-using populations. We hypothesized that perceived social support, as measured by the Social Provisions Scale (SPS), would have an inverse relationship with frequency of substance use, from subsections of the Addiction Severity Index (ASI) that estimate use over the past 30 days and over an individual's lifetime. METHODS: Using a cross-sectional design, we conducted secondary correlational analyses with pre-existing data to test our hypothesis in two separate samples made up of socially marginalized populations entering ASUD treatment programs. Sample 1: substance-using male prison inmates (n = 72, average age = 30.79) and Sample 2: primary methamphetamine-using men who have sex with men (n = 86, average age = 43.41). RESULTS: Significant negative correlations were found between SPS and lifetime use of alcohol, tobacco, and cannabis (r s  - 0.27, -0.39, -0.26; p-values 0.04, 0.001, 0.04, respectively) in Sample 1 and 30-day use of methamphetamine (r s  - 0.28; p-value 0.008) in Sample 2. DISCUSSION: Differences in results between the samples (lifetime vs 30-day use) may reflect psychosocial and contextual differences impacting perceived social support. Our findings provide support for an important link between perceived social support and frequency of substance use in socially stigmatized populations.