It is estimated that a majority of people who use psychostimulants, particularly methamphetamine (MA) and cocaine, experience withdrawal upon abstinence from sustained use. This review of clinical ...research reports the evidence regarding biomedical and behavioral treatments for psychostimulant withdrawal symptoms. It provides a framework for clinicians and scientists to increase impact on attenuating MA and cocaine withdrawal during initial and sustained abstinence. Articles reviewed included reports of controlled clinical trials (randomized or non‐randomized) reporting at least one withdrawal symptom among the outcomes or specifically studying patients in withdrawal. Potential efficacy for MA withdrawal is noted for a few medications (mirtazapine, naltrexone, bupropion) and repetitive transcranial magnetic stimulation during acute (first week), early protracted (weeks 2–4) and late protracted (> 4 weeks) withdrawal phases. Topiramate shows mixed evidence of efficacy for cocaine withdrawal. In general, there is inconsistent signal for biomedical and behavioral treatments on MA and cocaine withdrawal.
Psychiatry has always been characterized by a range of different models of and approaches to mental disorder, which have sometimes brought progress in clinical practice, but have often also been ...accompanied by critique from within and without the field. Psychiatric nosology has been a particular focus of debate in recent decades; successive editions of the DSM and ICD have strongly influenced both psychiatric practice and research, but have also led to assertions that psychiatry is in crisis, and to advocacy for entirely new paradigms for diagnosis and assessment. When thinking about etiology, many researchers currently refer to a biopsychosocial model, but this approach has received significant critique, being considered by some observers overly eclectic and vague. Despite the development of a range of evidence‐based pharmacotherapies and psychotherapies, current evidence points to both a treatment gap and a research‐practice gap in mental health. In this paper, after considering current clinical practice, we discuss some proposed novel perspectives that have recently achieved particular prominence and may significantly impact psychiatric practice and research in the future: clinical neuroscience and personalized pharmacotherapy; novel statistical approaches to psychiatric nosology, assessment and research; deinstitutionalization and community mental health care; the scale‐up of evidence‐based psychotherapy; digital phenotyping and digital therapies; and global mental health and task‐sharing approaches. We consider the extent to which proposed transitions from current practices to novel approaches reflect hype or hope. Our review indicates that each of the novel perspectives contributes important insights that allow hope for the future, but also that each provides only a partial view, and that any promise of a paradigm shift for the field is not well grounded. We conclude that there have been crucial advances in psychiatric diagnosis and treatment in recent decades; that, despite this important progress, there is considerable need for further improvements in assessment and intervention; and that such improvements will likely not be achieved by any specific paradigm shifts in psychiatric practice and research, but rather by incremental progress and iterative integration.
•Without Ibudilast, 30 mg methamphetamine infusion elevated sICAM-1, sVCAM-1, and cathepsin D in 60 min.•Without Ibudilast, 30 mg methamphetamine infusion elevated IL-6 in 360 min.•Ibudilast ...decreased methamphetamine-induced responses of sICAM-1, sVCAM-1, and cathepsin D compared to placebo.
Preclinical studies suggest that the non-selective phosphodiesterase inhibitor, Ibudilast (IBUD) may contribute to the treatment of methamphetamine (METH) use disorder through the attenuation of METH-induced inflammatory markers such as adhesion molecules, sICAM-1 and sVCAM-1, and cytokines, IL-6 and TNF-α.
The present study aimed to test whether treatment with IBUD can attenuate peripheral markers of inflammation during a METH challenge in an inpatient clinical trial of 11 patients.
This trial followed a randomized, within-subjects crossover design where participants received a METH challenge, during which five participants were treated with placebo then with IBUD, while the remaining six participants were treated with IBUD prior to placebo. Mixed effects regression modeled changes in peripheral markers of inflammation—sICAM-1, sVCAM-1, TNF-α, IL-6, MIF, and cathepsin D—by treatment condition, with measurements at baseline, 60 min post-METH infusion, and 360 min post-METH infusion. Results: While on placebo, sICAM-1, sVCAM-1, and cathepsin D significantly increased by 60 min post-METH infusion, while IL-6 significantly increased 360 min post-METH infusion. Treatment with IBUD significantly reduced METH-induced levels of sICAM-1, sVCAM-1, and cathepsin D at 60 min post-METH infusion.
Our findings demonstrate that IBUD attenuated acute pro-inflammatory effects of METH administration, which may have implications for treatment of METH use disorder.
This study aims to determine whether performance on the Iowa Gambling Task (IGT), a simulation of risk-taking when faced with loss, is associated with greater frequency of methamphetamine (MA) use ...and challenges reducing or stopping MA use. The parent mSTUDY is a Los Angeles County-based longitudinal study of substance use and HIV risk in predominately Black/African American and Latinx people assigned male at birth who have sex with men. The IGT was offered for a limited timeframe to mSTUDY participants, of whom 192 consented to and completed this one-time task. Separate random intercept binary logistic regressions tested whether the IGT total score and subscore for Blocks 4 and 5 (last 40 card draws) were associated with the outcomes, testing positive for MA in urine and self-reported inability to control or cease MA use in the past 6 months. Separate random intercept ordered logistic regressions tested whether IGT total score and subscore were associated with self-reported frequency of MA use in past 6 months. Higher IGT subscores for Blocks 4 and 5 (lower risk-taking) were associated with lower odds of testing MA-positive (adjusted odds ratio, AOR = 0.97, 95% CI 0.95, 0.99, p = .025) and less frequent MA use in the past 6 months (AOR = 0.96, 95% CI 0.94, 0.99, p = .006). Higher IGT total scores (lower risk-taking) were also associated with less frequent MA use (AOR = 0.99, 95% CI 0.97, 0.99, p = .038). Findings from this analysis suggest that IGT performance may be a useful indicator of MA use severity in nontreatment-seeking people.
Public Health Significance
This study indicates that greater tendency toward risk-taking during loss-as measured by the Iowa Gambling Task-is linked to more severe of methamphetamine use. Findings from this analysis provide information about the utility of the Iowa Gambling Task for assessing methamphetamine use severity and may help to identify treatment need.
Abstract Background and aims A 12‐week placebo‐controlled, sequential parallel Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT‐2) trial evaluated ...the effects of extended‐release injectable naltrexone plus extended‐release oral bupropion (NTX + BUPN) on methamphetamine (MA) use over two stages. This study reports on the previously unpublished stage 2 MA use in participants randomized at stage 1 to receive NTX + BUPN through both stages compared with those assigned to placebo. Design This is a secondary analysis of the US National Institute on Drug Abuse (NIDA) ADAPT‐2 network trial. Setting The parent ADAPT‐2 trial was carried out across multiple NIDA Clinical Trials Network (CTN) sites in the United States. Participants This analysis includes 403 people with MA use disorder who participated in the ADAPT‐2 CTN trial. Intervention and comparator NTX + BUPN was compared with placebo over the course of the trial. Measurement MA use was measured by urine drug screens conducted twice weekly for 12 weeks, then once in week 13 and once in week 16 post‐treatment follow‐up. Findings Participants on NTX + BUPN in stage 1 showed an additional 9.2% increase 95% confidence interval (CI), 0.09%–17.9%, P = 0.038 during stage 2 in their probability of testing negative for MA, with a total increase of 27.1% (95% CI, 13.2%–41.1%, P < 0.001) over the full 12 weeks of treatment. In contrast, participants on placebo in both stages increased in probability of testing MA‐negative by a total of 11.4% (95% CI, 4.1%–18.6%, P = 0.002) over all 12 weeks. The 12‐week increase among participants on NTX + BUPN was significantly greater—by 15.8% (95% CI, 4.5%–27.0%, P = 0.006)—than the increase among those on placebo. Conclusion For people with methamphetamine (MA) use disorder receiving treatment with extended‐release injectable naltrexone plus extended‐release oral bupropion (NTX + BUPN), continued treatment with NTX + BUPN after 6 weeks is associated with additional reductions in MA use up to 12 weeks.
Family rejection has negative health consequences for Latinx sexual minority men (LSMM). However, LSMM often reconcile with their families, a phenomenon cross-sectional studies miss. We analyzed ...longitudinal data from the Healthy Young Men’s Study in Los Angeles. We used individual fixed-effects Poisson regression to model changes over time in the associations among family support, drug use, and depressive symptoms. We found that (1) the initiation of drug use was associated with a 7.2% (Ratio=1.072, 95% CI 1.006 - 1.142, p = 0.03) increase in family support among LSMM who reported high depressive symptoms (depression subscale T-score ≥ 63) in at least one data wave; (2) a 1-unit increase in family support was associated with a 4.7% (RR = ;0.953, 95% CI 0.931 - 0.976, p < 0.001) decrease in the probability of high depressive symptoms; and (3) no significant association between a change in drug use and a change in high depressive symptoms. Over time, LSMM appear to benefit from the health effects of family support associated with Latinx family structures.
Starting in 2008, Vietnam’s national MMT program expanded quickly, but it is struggling with increasing attrition rates and poor adherence among patients. Several studies have reported on MMT ...retention and adherence, but no overview has yet been published. The objective of this study is to fill that gap and to review factors associated with retention and adherence in MMT in Vietnam.
A systematic search was conducted using databases of literature - Pubmed, Cochrane, Scopus, Academic search premiere, and SoINDEX. Peer-reviewed empirical studies with full text in English discussing retention attrition and adherence regarding MMT in Vietnam were selected. The results were synthesized using qualitative methods.
Adherence and retention rates varied among the 11 included studies. In general, patients in mountainous provinces had lower adherence and retention rates than those in big cities. Retention rates decreased with the studies’ follow-up period and had a downward trend over time. Factors associated with adherence and retention can be classified into three groups: individual, community, and institutional factors. Important individual factors areage, education, awareness of MMT and HIV, and co-occurring disorders and comorbidities. Stigma is the major community risk factor, and methadone daily dose, the distance between home and clinic, and clinic’s service hours are the three most important institutional factors.
The literature reviewed identifies important factors associated with MMT adherence and retention in Vietnam. The findings suggest further research exploring both subjective and objective factors and more policies to remove social and structural barriers to enhance treatment outcomes.
•In Vietnam, MMT adherence and retention rates have a downward trend over time and are lower in mountainous provinces.•Factors associated with adherence and retention are at individual, community, and institutional levels.•Important individual-level factors are age, education, awareness of MMT and HIV, co-occurring disorders, and comorbidities.•Stigma is the major community risk factor.•Suboptimal methadone doses, distance to clinic, and clinic service hours are the three most important institutional factors.
Pre-exposure prophylaxis (PrEP) is efficacious for HIV prevention. Black men who have sex with men (MSM) accounted for the largest proportion of new HIV diagnoses in the United States relative to ...other racial/ethnic groups. Black MSM who use substances are at an increased risk for HIV infection and are ideal candidates for PrEP, but barriers to maintaining PrEP adherence remain a concern. We assessed whether substance use behaviors are associated with initiation and adherence to PrEP among a sample of black MSM in the United States.
Data for this analysis come from the HIV Prevention Trails Network Study 073 (HPTN 073). Substance use behaviors-including alcohol, marijuana, poppers (ie, alkyl nitrites), and stimulants (ie, methamphetamine/cocaine use) including use of these substances before/during condomless anal intercourse (CAI)-were assessed longitudinally through self-report. PrEP adherence was assessed by pharmacological testing in blood. Generalized estimating equations were used to evaluate association between substance use behaviors and PrEP initiation and adherence.
Among 226 HIV-negative black MSM, the majority (60%) were 25+ years of age. Most of the substance use behaviors were not significantly associated with PrEP initiation or adherence. However, stimulant use before/during CAI was significantly associated with lower odds of PrEP adherence (adjusted odds ratio = 0.21, 95% confidence interval = 0.07 to 0.61; P = <0.01).
These findings suggest that PrEP adherence is feasible among black MSM who use substances. However, black MSM who engage in stimulant use before/during CAI may present a unique group for additional study and support with enhanced behavioral health and support services.
To longitudinally evaluate differences in HIV viral suppression (<200 copies/ml) by intersections of race/ethnicity, gender, and psychosocial issues in people with HIV in the Los Angeles County ...Medical Care Coordination Program.
We analyzed 74 649 viral load measurements over 10 184 people with HIV enrolled in the Medical Care Coordination Program between January 1, 2013 and March 1, 2020.Methods: We fit Bayesian logistic hierarchical random effects models to test interactions between gender, race/ethnicity, and a psychosocial acuity score on viral suppression over time from 1 year prior to program enrollment to 24 months after enrollment.
The probability of viral suppression declined prior to enrollment, then increased and stabilized by 6 months after enrollment. Black/African American patients with low and moderate psychosocial acuity scores did not achieve the same increase in percentage of viral suppression as those in other racial/ethnic groups. Transgender women with high psychosocial acuity scores took longer (about 1 year) to achieve the same percentage of viral suppression as clients of other gender identities.
Some racial/ethnic and gender disparities in viral suppression persisted after enrollment in the Los Angeles County Medical Care Coordination Program while accounting for psychosocial acuity score, which may be explained by factors not assessed in the program.
Abstract Objective To compare modafinil to placebo for reducing methamphetamine (MA) use, improving retention, and reducing depressive symptoms and MA cravings. Rates of adverse events and cigarette ...smoking with modafinil versus placebo were also compared. Methods Following a 2-week, non-medication lead-in period, 71 treatment-seeking MA-dependent participants were randomly assigned to modafinil (400 mg once daily; N = 34) or placebo (once daily; N = 37) for 12 weeks under double-blind conditions. Participants attended clinic thrice-weekly to provide urine samples analyzed for MA-metabolite, to complete research assessments, and to receive contingency management and weekly cognitive behavioral therapy (CBT) sessions. Results There were no statistically significant effects for modafinil on MA use, retention, depressive symptoms, or MA cravings in pre-planned analyses. Outcomes for retention and MA use favored modafinil in a post hoc analysis among participants with low CBT attendance and among participants with baseline high-frequency of MA use (MA use on >18 of past 30 days), but did not reach statistical significance in these small subgroups. Modafinil was safe and well tolerated and did not increase cigarette smoking. Conclusions Modafinil was no more effective than placebo at 400 mg daily in a general sample of MA users. A post hoc analysis showing a trend favoring modafinil among subgroups with baseline high-frequency MA use and low CBT attendance suggests that further evaluation of modafinil in MA users is warranted.
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