SynthesisCNS drugs2026
Approved Medications for Substance Use Disorders: An Umbrella Review of Systematic Reviews and Completed Phase 3 Randomized Controlled Trials.
Synthesis in CNS drugs, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesThis umbrella review of systematic reviews, meta-analyses, and completed phase 3 randomized controlled trials (RCTs) over the past 10 years covers approved pharmacological treatments for substance use disorders (SUD) worldwide, providing clinicians and researchers with a detailed analysis of current pharmacotherapies and bridging the gap between evolving pharmacological interventions and clinical practice.
methodsThis PROSPERO-registered umbrella review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Peer-reviewed systematic reviews were selected to include systematic reviews of RCTs and meta-analyses that examined approved medications for treatment, withdrawal management, or overdose reversal of SUD in all populations. Reviews published in peer-reviewed journals from 1 January 2016 to 1 January 2026, including medications that received worldwide approvals from World Health Organization (WHO)-listed Authorities plus those in the ten most populous countries were included. Reviews of preclinical studies and those not meeting systematic review standards or missing required data were excluded. We also included completed phase 3 SUD medications, including only RCTs with posted results from 2016 to 2026; preclinical studies and those with missing required data were excluded. We searched PubMed, MEDLINE, and the Cochrane Library databases for systematic reviews using keywords related to SUD. We also searched for phase 3 medications on the WHO International Clinical Trials Registry Platform. Risk of bias and methodological quality were assessed using the Risk if Bias in Systematic Reviews (ROBIS) and A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) tools for systematic reviews and using the Cochrane risk of bias (RoB2) tool for phase 3 RCTs. Two independent reviewers conducted the selection process, resolving discrepancies through discussion, consultation with a third reviewer, and reaching consensus. The results were synthesized narratively and presented by each medication in summaries and tables.
resultsSixteen systematic reviews were reviewed, containing 371 RCTs (n = 131,965) and 62 observational studies (OS) (n = 229,225) examining 41 approved medications (with 25 distinct molecules) for SUD worldwide as of 1 January 2026: Eighty-six RCTs (n = 18,643) covering seven medications for alcohol use disorder (AUD), showed a reduction of risk of returning to any drinking ranging from 7 to 17% compared with placebo; three for alcohol withdrawal/intoxication. A total of 49 RCTs (n = 7804) and 21 OS (n = 155,111) covering 12 medications for opioid use disorder (OUD), showed that the highest abstinence rates ranged from 41 to 43% compared with 5% in placebo. Forty-one OS (n = 74,114) covering nine medications for opioid overdose reversal, with survival rates ranging from 92 to 98%; one for opioid withdrawal. A total of 223 RCTs (n = 104,524) covering eight medications for tobacco use disorder (TUD), showed 1.3-2.3 times more likelihood to experience abstinence compared with placebo; and 13 RCTs (n = 994) covering one medication in sedative-hypnotic or anxiolytic use disorder (SHAUD) for benzodiazepine overdose reversal. Four completed phase 3 RCTs with posted results were reviewed, which included 1026 participants examining four pipeline medication treatments for SUD worldwide as of 1 January 2026: three RCTs (n = 623) covering three medications for AUD, and one RCT (n = 403) covering one combination medication treatment for stimulant use disorder (StUD).
conclusionsRecent advancements in medications for SUD have expanded the range of pharmacologic treatments available for clinical practice. Effective medications are available for tobacco, opioid, and alcohol use disorders, and promising medications are emerging beyond the currently approved treatment landscape. TRIAL REGISTRY: PROSPERO ID: CRD420251036330.
Identifiers
42776462What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.