The Changing Landscape of Substance Use Disorders

PLoS Med 2018; 15:e1002715

BACKGROUND: Clinical guidelines recommend psychosocial interventions for cocaine and/or amphetamine addiction as first-line treatment, but it is still unclear which intervention, if any, should be offered first. We aimed to estimate the comparative effectiveness of all available psychosocial interventions (alone or in combination) for the short- and long-term treatment of people with cocaine and/or amphetamine addiction.

METHODS AND FINDINGS: We searched published and unpublished randomized controlled trials (RCTs) comparing any structured psychosocial intervention against an active control or treatment as usual (TAU) for the treatment of cocaine and/or amphetamine addiction in adults. Primary outcome measures were efficacy (proportion of patients in abstinence, assessed by urinalysis) and acceptability (proportion of patients who dropped out due to any cause) at the end of treatment, but we also measured the acute (12 weeks) and long-term (longest duration of study follow-up) effects of the interventions and the longest duration of abstinence. Odds ratios (ORs) and standardized mean differences were estimated using pairwise and network meta-analysis with random effects. The risk of bias of the included studies was assessed with the Cochrane tool, and the strength of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We followed the PRISMA for Network Meta-Analyses (PRISMA-NMA) guidelines, and the protocol was registered in PROSPERO (CRD 42017042900). We included 50 RCTs evaluating 12 psychosocial interventions or TAU in 6,942 participants. The strength of evidence ranged from high to very low. Compared with TAU, contingency management (CM) plus community reinforcement approach was the only intervention that increased the number of abstinent patients at the end of treatment (OR 2.84, 95% CI 1.24–6.51, p=0.013), and also at 12 weeks (OR 7.60, 95% CI 2.03–28.37, p=0.002) and at longest follow-up (OR 3.08, 95% CI 1.33–7.17, p=0.008). At the end of treatment, CM plus community reinforcement approach had the highest number of statistically significant results in head-to-head comparisons, being more efficacious than cognitive behavioral therapy (CBT) (OR 2.44, 95% CI 1.02–5.88, p=0.045), noncontingent rewards (OR 3.31, 95% CI 1.32–8.28, p=0.010), and 12-step program plus noncontingent rewards (OR 4.07, 95% CI 1.13–14.69, p=0.031). CM plus community reinforcement approach was also associated with fewer dropouts than TAU, both at 12 weeks and the end of treatment (OR 3.92, p<0.001, and 3.63, p<0.001, respectively). At the longest follow-up, community reinforcement approach was more effective than noncontingent rewards, supportive-expressive psychodynamic therapy, TAU, and 12-step program (OR ranging between 2.71, p=0.026, and 4.58, p=0.001), but the combination of community reinforcement approach with CM was superior also to CBT alone, CM alone, CM plus CBT, and 12-step program plus noncontingent rewards (ORs between 2.50, p=0.039, and 5.22, p<0.001). The main limitations of our study were the quality of included studies and the lack of blinding, which may have increased the risk of performance bias. However, our analyses were based on objective outcomes, which are less likely to be biased.

CONCLUSIONS: To our knowledge, this network meta-analysis is the most comprehensive synthesis of data for psychosocial interventions in individuals with cocaine and/or amphetamine addiction. Our findings provide the best evidence base currently available to guide decision-making about psychosocial interventions for individuals with cocaine and/or amphetamine addiction and should inform patients, clinicians, and policy-makers.

Copyright 2018 De Crescenzo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Eur Arch Psychiatry Clin Neurosci 2018. doi: 10.1007/s00406-018-0970-7

With the increasing push to legalize cannabis in Western nations, there is a need to gauge the potential impact of this policy change on vulnerable populations, such as those with mental illness, including schizophrenia, mood, and anxiety disorders. This is particularly important as there are strong motives in these individuals to seek short-term reward (e.g. “getting high”). Nonetheless, data to support the beneficial effects of cannabis use in psychiatric populations are limited, and potential harms in patients with psychotic and mood disorders have been increasingly documented. This article reviews the effects of cannabis in people with mental illness. Then, we provide a reconciliation of the addiction vulnerability and allostatic hypotheses to explain comorbidity addiction in mentally ill cannabis users, as well as to further aid in developing a rational framework for the assessment and treatment of problematic cannabis use in these patients.

Copyright 2018 Springer-Verlag GmbH Germany, part of Springer Nature.

Drug Alcohol Depend 2018; 184:12–17

BACKGROUND: Tobacco use is prevalent among persons with alcohol abuse and dependence. Varenicline has been shown to be the most effective pharmacotherapy for smoking cessation and may decrease alcohol consumption. The purpose of this study was to evaluate the efficacy of 12 weeks of varenicline for increasing smoking abstinence rates in smokers with alcohol abuse or dependence.

METHODS: Participants were eligible for enrollment if they were 18 years or older, smoked 10 or more cigarettes per day for at least 6 months, had current alcohol abuse or dependence, and were interested in quitting smoking. Participants were randomly assigned to receive 12 weeks of varenicline 1 mg twice daily or matching placebo. The primary end point was 7-day point prevalence smoking abstinence at week 12.

RESULTS: The 7-day point prevalence smoking abstinence rate at 12 weeks was significantly higher with varenicline (n = 16) than placebo (n = 17) (43.8% versus 5.9%; P = 0.01). At 24 weeks, the 7-day point prevalence smoking abstinence rate was still significantly higher with varenicline than placebo (31.3% versus 0%; P = 0.02). At 12 weeks, mean (SD) drinks per drinking day was significantly lower with varenicline than placebo (5.7 [3.9] versus 9.0 [5.3] drinks; treatment effect estimate, −2.8 [90% CI, −6.6 to −1.0]). Adverse events were minor and comparable to varenicline clinical trials.

CONCLUSIONS: Varenicline is safe and efficacious for increasing smoking abstinence rates in smokers with alcohol abuse or dependence. Varenicline may decrease alcohol consumption in this population of smokers.

Copyright 2018. Reprinted with permission from Elsevier.

Lancet Psychiatry 2019; 6:25–34

BACKGROUND: The self-medication hypothesis postulates that the high prevalence of smoking in patients with psychosis can be explained by the ameliorating effect of smoking on symptoms. However, there are few large prospective studies testing this hypothesis. We aimed to examine the multicross-sectional and prospective associations of changes in smoking behavior with symptoms and quality of life.

METHODS: In this prospective cohort study we recruited patients with a nonaffective psychosis (N=1094), unaffected siblings (N=1047), and healthy controls (N=579). Patients aged between 16 and 50 years and diagnosed with a nonaffective psychosis according to DSM-IV were recruited by clinicians from four university medical centers and 36 associated mental health-care institutions in the Netherlands and Belgium between Jan 13, 2004, and March 6, 2014. Smoking status and number of cigarettes per day were assessed at baseline, and at 3-year and 6-year follow-up using the Composite International Diagnostic Interview (CIDI). Symptom frequency was self-rated with the Community Assessment of Psychotic Experience (CAPE), and quality of life was assessed by the WHO Quality of Life (WHOQOL) schedule. Multiple linear mixed-effects regression analyses were done accounting for multiple confounders.

FINDINGS: At baseline, 729 (67%) of 1094 of patients smoked (mean 17·5 cigarettes per day, SD 8·8) compared with 401 (38%) of 1047 siblings and 145 (25%) of 579 healthy controls. Multicross-sectional results of linear mixed-effects analyses showed that smoking in patients and siblings was associated with more frequent positive symptoms (estimate 0·14, SE 0·02, p<0·0001 in patients; 0·03, 0·01, p=0·0019 in siblings), negative symptoms (0·15, 0·03, p<0·0001 in patients; 0·09, 0·02, p<0·0001 in siblings), and depressive symptoms (0·12, 0·03 p<0·0001 in patients; 0·08, 0·02 p<0·0001 in siblings) and lower quality of life (−0·59, 0·11, p<0·0001 in patients; −0·31, 0·09, p=0·0002 in siblings) than nonsmokers. In controls, smoking was associated with significantly higher frequency of subclinical positive symptoms (0·03, 0·01, p=0·0016) and depressive symptoms (0·05, 0·03, p=0·0432) than in participants who did not smoke. Patients who started to smoke during follow-up showed a significant increase in self-reported symptoms, particularly positive symptoms (0·161, 0·077, p=0·0381), whereas smoking cessation was not associated with changes in symptoms or quality of life compared with those who showed no change in smoking behavior. Similar results were obtained for the changes in the number of cigarettes smoked.

INTERPRETATION: Our findings do not empirically support the self-medication hypothesis. The absence of long-term symptomatic relief from smoking should encourage clinicians to help patients with psychosis to quit smoking.

Copyright 2019. Reprinted with permission from Elsevier.

Neuropsychopharmacology 2018; 43:173–194

Cannabis use disorder (CUD) commonly occurs and carries a notable economic and functional burden at both individual and societal levels. While there are no clearly efficacious medication treatments for CUD, 20 years of committed and high-quality research in the human laboratory and clinical settings have resulted in medications with demonstrated effectiveness in the treatment of cannabis withdrawal, the ability to reduce cannabis use, and results that point to promising future work. The current state of pharmacology research for CUD highlights the need to consider particular characteristics of patients, such as gender, impulsivity, and severity of cannabis use, when selecting a medication in the off-label treatment of CUD or cannabis withdrawal. As a field, the body of work also exposes some areas in need of improvement in study design, selection of outcome measures, interpretation of results, and the overall process of evaluating candidate medications. Coming to a consensus as a field and addressing these gaps in future research will likely lend itself to further advances in improving the lives of patients with CUD.

Reprinted with permission from Springer Nature.

Lancet 2018; 391:309–318

BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX.

METHODS: We initiated this 24 week, open-label, randomized controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used nonprescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomization (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any nonstudy opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433.

FINDINGS: Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (N=283) or BUP-NX (N=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, N=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10–1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, N=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favored BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group).

INTERPRETATION: In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications.

Copyright 2018. Reprinted with permission from Elsevier.

Curr Psychiatry Rep 2014; 16:436

Adolescents and young adults with substance use disorders (SUD) and attention deficit/hyperactivity disorder (ADHD) are increasingly presenting in clinical practice. The overlap and role of treatment for these co-occurring disorders remains unclear. A review of the literature was conducted to highlight and update recent evidence on the overlap of ADHD and SUD, the role of ADHD medication on later SUD, and the treatment of ADHD and SUD in adolescents and young adults. Recent work continues to highlight the high risk for comorbid ADHD in patients with SUD; and conversely, the high risk for SUD developing in ADHD across the lifespan, particularly in the context of comorbid conduct disorder. Although the data remains discordant, it appears that ADHD pharmacotherapy does not increase the risk for SUD. Medication treatment alone does not appear to be particularly effective in treating SUD in currently active substance abusing individuals with ADHD. Structured therapies may be effective in treating adolescents and young adults with ADHD and SUD. Further controlled trials evaluating the sequence and effect of structured psychotherapies and/or ADHD pharmacotherapy on SUD relapse in these groups are warranted.

Reprinted with permission from Springer Nature.

Drug Alcohol Depend 2016; 163(Suppl 1):S13–S18

BACKGROUND: The core clinical symptoms of addiction include an enhanced incentive for drug taking (craving), impaired self-control (impulsivity and compulsivity), emotional dysregulation (negative mood) and increased stress reactivity. Symptoms related to impaired self-control involve reduced activity in anterior cingulate cortex (ACC), adjacent prefrontal cortex (mPFC) and other brain areas. Behavioral training such as mindfulness meditation can increase the function of control networks including those leading to improved emotion regulation and thus may be a promising approach for the treatment of addiction.

METHODS: In a series of randomized controlled trials (RCTs), we tested whether increased ACC/mPFC activity is related to better self-control abilities in executive functions, emotion regulation and stress response in healthy and addicted populations. After a brief mindfulness training (Integrative Body-Mind Training, IBMT), we used the Positive and Negative Affect Schedule (PANAS) and Profile of Mood States (POMS) to measure emotion regulation, salivary cortisol for the stress response and fMRI for brain functional and DTI structural changes. Relaxation training was used to serve as an active control.

RESULTS: In both smokers and nonsmokers, improved self-control abilities in emotion regulation and stress reduction were found after training and these changes were related to increased ACC/mPFC activity following training. Compared with nonsmokers, smokers showed reduced ACC/mPFC activity in the self-control network before training, and these deficits were ameliorated after training.

Conclusions: These results indicate that promoting emotion regulation and improving ACC/mPFC brain activity can help for addiction prevention and treatment.

Copyright 2016. Reprinted with permission from Elsevier.

Psychol Addict Behav 2017; 31:847–861

Cognitive–behavioral therapy (CBT) approaches have among the highest level of empirical support for the treatment of drug and alcohol use disorders. As Psychology of Addictive Behaviors marks its 30th anniversary, we review the evolution of CBT for the addictions through the lens of the Stage Model of Behavioral Therapies Development. The large evidence base from Stage II randomized clinical trials indicates a modest effect size with evidence of relatively durable effects, but limited diffusion in clinical practice, as is the case for most empirically validated approaches for mental health and addictive disorders. Technology may provide a means for CBT interventions to circumvent the “implementation cliff” in Stages III–V by offering a flexible, low-cost, standardized means of disseminating CBT in a range of novel settings and populations. Moreover, returning to Stage I to reconnect clinical applications of CBT to recent developments in cognitive science and neuroscience holds great promise for accelerating understanding of mechanisms of action. It is critical that CBT not be considered as a static intervention, but rather 1 that constantly evolves and is refined through the stage model until the field achieves a maximally powerful intervention that addresses core features of the addictions.

Reprinted with permission from the American Psychological Association.