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Interventions for Substance Use Disorders in Adolescents: A Systematic Review

Author/s: 
Steele, D.W., Becker, S.J., Danko, K.J., Balk, E.M., Saldanha, I.J., Adam, G.P., Bagley, S.M., Friedman, C., Spirito, A., Scott, K., Ntzani, E.E., Saeed, I., Smith, B., Popp J., Trikalinos, T.A.

Structured Abstract

Objectives. This systematic review (SR) synthesizes the literature on behavioral, pharmacologic, and combined interventions for adolescents ages 12 to 20 years with problematic substance use or substance use disorder. We included interventions designed to achieve abstinence, reduce use quantity and frequency, improve functional outcomes, and reduce substance-related harms.

Data sources. We conducted literature searches in MEDLINE, the Cochrane CENTRAL Trials Registry, Embase, CINAHL, and PsycINFO to identify primary studies meeting eligibility criteria through November 1, 2019.

Review methods. Studies were extracted into the Systematic Review Data Repository. We categorized interventions into seven primary intervention components: motivational interviewing (MI), family focused therapy (Fam), cognitive behavioral therapy (CBT), psychoeducation, contingency management (CM), peer group therapy, and intensive case management. We conducted meta-analyses of comparative studies and evaluated the strength of evidence (SoE). The PROSPERO protocol registration number is CRD42018115388.

Results. The literature search yielded 33,272 citations, of which 118 studies were included. Motivational interviewing reduced heavy alcohol use days by 0.7 days/month, alcohol use days by 1.2 days/month, and overall substance use problems by a standardized mean difference of 0.5, compared with treatment as usual. Brief MI did not reduce cannabis use days (net mean difference of 0). Across multiple intensive interventions, Fam was most effective, reducing alcohol use days by 3.5 days/month compared with treatment as usual. No intensive interventions reduced cannabis use days. Pharmacologic treatment of opioid use disorder led to a more than 4 times greater likelihood of abstinence with extended courses (2 to 3 months) of buprenorphine compared to short courses (14 to 28 days).

Conclusions. Brief interventions: MI reduces heavy alcohol use (low SoE), alcohol use days (moderate SoE), and substance use–related problems (low SoE) but does not reduce cannabis use days (moderate SoE). Nonbrief interventions: Fam may be most effective in reducing alcohol use (low SoE). More research is needed to identify other effective intensive behavioral interventions for alcohol use disorder. Intensive interventions did not appear to decrease cannabis use (low SoE). Some interventions (CBT, CBT+MI, and CBT+MI+CM) were associated with increased cannabis use (low SoE). Both MI and CBT reduce combined alcohol and other drug use (low SoE). Combined CBT+MI reduces illicit drug use (low SoE). Subgroup analyses of interest (male vs. female, racial and ethnic minorities, socioeconomic status, and family characteristics) were sparse, precluding conclusions regarding differential effects. Pharmacological interventions: longer courses of buprenorphine (2–3 months) are more effective than shorter courses (14–28 days) to reduce opioid use and achieve abstinence (low SoE). SRs in the college settings support use of brief interventions for students with any use, heavy or problematic use. More research is needed to identify the most effective combinations of behavioral and pharmacologic treatments for opioid, alcohol, and cannabis use disorders.

Citation

Suggested citation: Steele DW, Becker SJ, Danko KJ, Balk EM, Saldanha IJ, Adam GP, Bagley SM, Friedman C, Spirito A, Scott K, Ntzani EE, Saeed I, Smith B, Popp J, Trikalinos TA. Interventions for Substance Use Disorders in Adolescents: A Systematic Review. Comparative Effectiveness Review No. 225. (Prepared by the Brown Evidence-based Practice Center under Contract No. 290-2015-00002-I.) AHRQ Publication No. 20-EHC014. Rockville, MD: Agency for Healthcare Research and Quality. May 2020. Posted final reports are located on the Effective Health Care Program search page. DOI: https://doi.org/10.23970/AHRQEPCCER225.

Keywords 
substance abuse

Nonopioid Pharmacologic Treatments for Chronic Pain. Comparative Effectiveness Review No. 228

Author/s: 
McDonagh, MS, Selph, SS, Buckley, DI, Holmes, RS, Mauer, K, Ramirez, S, Hsu, FC, Dana, T, Fu, R, Chou

Objectives. To evaluate the effectiveness and comparative effectiveness of nonopioid pharmacologic agents in patients with specific types of chronic pain, considering effects on pain, function, quality of life, and adverse events.

Data sources. Electronic databases (Ovid® MEDLINE®, Embase®, PsycINFO®, CINAHL®, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) through September 10, 2019, reference lists, data requests, and previous reviews.

Review methods. Randomized controlled trials (RCTs) of nonopioid pharmacologic agents in patients with chronic pain were selected using predefined criteria and dual review. This review focused on seven common chronic pain conditions (neuropathic pain, fibromyalgia, osteoarthritis, inflammatory arthritis, low back pain, chronic headache, sickle cell disease), with effects analyzed at short term (1 to <6 months following treatment completion), intermediate term (≥6 to <12 months), and long term (≥12 months). Magnitude of effects were described as small, moderate, or large using previously defined criteria, and strength of evidence was assessed. Meta-analyses were conducted where data allowed, stratified by duration within each intervention type, using random effects models. We evaluated effect modification through subgroup and sensitivity analyses, including specific drug, dose, study quality, and pain type.

Results. We included 185 RCTs in 221 publications and 5 systematic reviews. In the short term, anticonvulsants (pregabalin, gabapentin, and oxcarbazepine for neuropathic pain, pregabalin/gabapentin for fibromyalgia), serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants (duloxetine for neuropathic pain, fibromyalgia, osteoarthritis, and low back pain, milnacipran for fibromyalgia), and nonsteroidal anti-inflammatory drugs (NSAIDs) (for osteoarthritis and inflammatory arthritis) were associated with mostly small improvements (e.g., 5 to 20 points on a 0 to 100 scale) in pain and function. Function was not found to be improved with duloxetine for low back pain or pregabalin/gabapentin for neuropathic pain. Moderate improvement in quality of life was seen with duloxetine in patients with neuropathic pain, and small improvements in patients with osteoarthritis, but evidence was insufficient to draw conclusions for other drugs and conditions. While most comparisons of drugs and doses did not identify differences, diclofenac improved pain and function moderately more than celecoxib. In the intermediate term, limited evidence (1 RCT) showed memantine moderately improved pain, function, and quality of life in patients with fibromyalgia; improvements in pain, but not function, were maintained in the intermediate term with duloxetine and milnacipran for fibromyalgia. Other drugs studied, including acetaminophen (osteoarthritis), capsaicin (neuropathic pain), cannabis (neuropathic pain), amitriptyline (fibromyalgia, neuropathic pain), and cyclobenzaprine (fibromyalgia) had no clear effects. Withdrawal from study due to adverse events was significantly increased with nonopioid drugs, with the greatest increase over placebo seen with cannabis. Large increases in risk of adverse events were seen with pregabalin (blurred vision, cognitive effects, dizziness, peripheral edema, sedation, and weight gain), gabapentin (blurred vision, cognitive effects, sedation, weight gain), and cannabis (nausea, dizziness). Dose viii reductions reduced the risk of some adverse events with SNRI antidepressants. In the short term small increases in risk of major coronary events and moderate increases in serious gastrointestinal events (both short and long term) were found with NSAIDs.

Conclusions. In the short term, small improvements in pain and/or function were seen with SNRI antidepressants for neuropathic pain, fibromyalgia, osteoarthritis, and low back pain; pregabalin/gabapentin for neuropathic pain and fibromyalgia; oxcarbazepine for neuropathic pain; and NSAIDs for osteoarthritis and inflammatory arthritis. Improvement in function was not found with duloxetine for low back pain and pregabalin/gabapentin for neuropathic pain. Intermediate- and long-term outcomes were mostly not assessed. Increased incidence of drug class–specific adverse events led to withdrawal from treatment in some patients, suggesting that careful consideration of patient characteristics is needed in selecting nonopioid drug treatments.

Keywords 
chronic pain non-opioid treatment anticonvulsants serotonin-norepinephrine reuptake inhibitor nonsteroidal anti-inflammatory drugs NSAID SNRI cannabis

Pharmacotherapy for the Treatment of Cannabis Use Disorder: A Systematic Review

Author/s: 
Kondo, K.K., Morasco, B.J., Nugent S.M., O'Neil, ME, Ayers, C.K., Freeman, M., Kansagara, D.

BACKGROUND:

Cannabis use disorder (CUD) is a growing concern, and evidence-based data are needed to inform treatment options.

PURPOSE:

To review the benefits and risks of pharmacotherapies for the treatment of CUD.

DATA SOURCES:

MEDLINE, PsycINFO, Cochrane Database of Systematic Reviews, and clinical trial registries from inception through September 2019.

STUDY SELECTION:

Pharmacotherapy trials of adults or adolescents with CUD that targeted cannabis abstinence or reduction, treatment retention, withdrawal symptoms, and other outcomes.

DATA EXTRACTION:

Data were abstracted by 1 investigator and confirmed by a second. Study quality was dually assessed, and strength of evidence (SOE) was determined by consensus according to standard criteria.

DATA SYNTHESIS:

Across 26 trials, the evidence was largely insufficient. Low-strength evidence was found that selective serotonin reuptake inhibitors (SSRIs) do not reduce cannabis use or improve treatment retention. Low- to moderate-strength evidence was found that buspirone does not improve outcomes and that cannabinoids do not increase abstinence rates (moderate SOE), reduce cannabis use (low SOE), or increase treatment retention (low SOE). Across all drug studies, no consistent evidence of increased harm was found.

LIMITATIONS:

Few methodologically rigorous trials have been done. Existing trials are hampered by small sample sizes, high attrition rates, and heterogeneity of concurrent interventions and outcomes assessment.

CONCLUSION:

Although data on pharmacologic interventions for CUD are scarce, evidence exists that several drug classes, including cannabinoids and SSRIs, are ineffective. Because of increasing access to and use of cannabis in the general population, along with a high prevalence of CUD among current cannabis users, an urgent need exists for more research to identify effective pharmacologic treatments.

PRIMARY FUNDING SOURCE:

U.S. Department of Veterans Affairs. (PROSPERO: CRD42018108064).

Therapeutic use of cannabis and cannabinoids: an evidence mapping and appraisal of systematic reviews

Author/s: 
Montero-Oleas, N, Arevalo-Rodriguez, I, Nunez-Gonzalez, S, Viteri-Garcia, A, Simancas-Racines, D

Background

Although cannabis and cannabinoids are widely used with therapeutic purposes, their claimed efficacy is highly controversial. For this reason, medical cannabis use is a broad field of research that is rapidly expanding. Our objectives are to identify, characterize, appraise, and organize the current available evidence surrounding therapeutic use of cannabis and cannabinoids, using evidence maps.

Methods

We searched PubMed, EMBASE, The Cochrane Library and CINAHL, to identify systematic reviews (SRs) published from their inception up to December 2017. Two authors assessed eligibility and extracted data independently. We assessed methodological quality of the included SRs using the AMSTAR tool. To illustrate the extent of use of medical cannabis, we organized the results according to identified PICO questions using bubble plots corresponding to different clinical scenarios.

Results

A total of 44 SRs published between 2001 and 2017 were included in this evidence mapping with data from 158 individual studies. We extracted 96 PICO questions in the following medical conditions: multiple sclerosis, movement disorders (e.g. Tourette Syndrome, Parkinson Disease), psychiatry conditions, Alzheimer disease, epilepsy, acute and chronic pain, cancer, neuropathic pain, symptoms related to cancer (e.g. emesis and anorexia related with chemotherapy), rheumatic disorders, HIV-related symptoms, glaucoma, and COPD. The evidence about these conditions is heterogeneous regarding the conclusions and the quality of the individual primary studies. The quality of the SRs was moderate to high according to AMSTAR scores.

Conclusions

Evidence on medical uses of cannabis is broad. However, due to methodological limitations, conclusions were weak in most of the assessed comparisons. Evidence mapping methodology is useful to perform an overview of available research, since it is possible to systematically describe the extent and distribution of evidence, and to organize scattered data.

Keywords 
cannabis cannabinoids therapeutic use evidence mapping medical marijuana

Severe Pulmonary Disease Associated with Electronic-Cigarette–Product Use — Interim Guidance

Author/s: 
Schier, JG, Meiman, JG, Layden, J, Mikosz, CA, VanFrank, B, King, BA, Salvatore, PP, Weissman, DN, Thomas, J, Melstrom, PC, Baldwin, GT, Parker, EM, Courtney-Long, EA, Krishnasamy, VP, Pickens, CM, Evans, ME, Tsay, SV, Powell, KM, Kiernan, EA, Marynak, KL, Adjemian, J, Holton, K, Armour, BS, England, LJ, Briss, PA, Houry, D, Hacker, KA, Reagan-Steiner, S, Zaki, S, Meaney-Delman, D, CDC 2019 Lung Injury Response Group

On September 6, 2019, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr). As of August 27, 2019, 215 possible cases of severe pulmonary disease associated with the use of electronic cigarette (e-cigarette) products (e.g., devices, liquids, refill pods, and cartridges) had been reported to CDC by 25 state health departments. E-cigarettes are devices that produce an aerosol by heating a liquid containing various chemicals, including nicotine, flavorings, and other additives (e.g., propellants, solvents, and oils). Users inhale the aerosol, including any additives, into their lungs. Aerosols produced by e-cigarettes can contain harmful or potentially harmful substances, including heavy metals such as lead, volatile organic compounds, ultrafine particles, cancer-causing chemicals, or other agents such as chemicals used for cleaning the device (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, or other drugs; for example, "dabbing" involves superheating substances that contain high concentrations of THC and other plant compounds (e.g., cannabidiol) with the intent of inhaling the aerosol. E-cigarette users could potentially add other substances to the devices. This report summarizes available information and provides interim case definitions and guidance for reporting possible cases of severe pulmonary disease. The guidance in this report reflects data available as of September 6, 2019; guidance will be updated as additional information becomes available.

Keywords 
e-cigarettes pulmonary disease nicotine cannabis vaping

Clinicians’ Guide to Cannabidiol and Hemp Oils

Author/s: 
VanDolah H.J., Bauer, B.A., Mauck, K.F.

Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana. In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils. There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction. Care must be taken when directing patients toward CBD products because there is little regulation, and studies have found inaccurate labeling of CBD and tetrahydrocannabinol quantities. This article provides an overview of the scientific work on cannabinoids, CBD, and hemp oil and the distinction between marijuana, hemp, and the different components of CBD and hemp oil products. We summarize the current legal status of CBD and hemp oils in the United States and provide a guide to identifying higher-quality products so that clinicians can advise their patients on the safest and most evidence-based formulations. This review is based on a PubMed search using the terms CBD, cannabidiol, hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most up-to-date information were selected for inclusion.

Keywords 
cannabidoil cannabis

Deficient Functioning of Frontostriatal Circuits During the Resolution of Cognitive Conflict in Cannabis-Using Youth

Author/s: 
Cyr, M., Tau, G.Z., Fontaine, M., Levin, F.R., Marsh, R.

Abstract

OBJECTIVE:

Disturbances in self-regulatory control are involved in the initiation and maintenance of addiction, including cannabis use disorder. In adults, long-term cannabis use is associated with disturbances in frontostriatal circuits during tasks that require the engagement of self-regulatory control, including the resolution of cognitive conflict. Understudied are the behavioral and neural correlates of these processes earlier in the course of cannabis use disentangled from effects of long-term use. The present study investigated the functioning of frontostriatal circuits during the resolution of cognitive conflict in cannabis-using youth.

METHOD:

Functional magnetic resonance imaging data were acquired from 28 cannabis-using youth and 32 age-matched healthy participants during the performance of a Simon task. General linear modeling was used to compare patterns of brain activation during correct responses to conflict stimuli across groups. Psychophysiologic interaction analyses were used to examine conflict-related frontostriatalconnectivity across groups. Associations of frontostriatal activation and connectivity with cannabis use measures were explored.

RESULTS:

Decreased conflict-related activity was detected in cannabis-using versus healthy control youth in frontostriatal regions, including the ventromedial prefrontal cortex, striatum, pallidum, and thalamus. Frontostriatal connectivity did not differ across groups, but negative connectivity between the ventromedial prefrontal cortex and striatum was detected in the 2 groups.

CONCLUSION:

These findings are consistent with previous reports of cannabis-associated disturbances in frontostriatal circuits in adults and point to the specific influence of cannabis on neurodevelopmental changes in youth. Future studies should examine whether frontostriatalfunctioning is a reliable marker of cannabis use disorder severity and a potential target for circuit-based interventions.

Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved

Keywords 
cannabis use frontostriatal circuits functional magnetic resonance imaging resolution of cognitive conflict youth
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