Disulfiram for Alcohol Use Disorder: A Comprehensive Clinical Guide

Overview

Disulfiram — sold under the brand name Antabuse — is the oldest FDA-approved medication for alcohol use disorder (AUD), having been in clinical use since the 1940s [corpus-gap]. It sits alongside naltrexone and acamprosate as one of only three FDA-approved pharmacotherapies for the condition, yet it remains the most polarizing of the three — and for good reason.

The honest summary of disulfiram is this: under supervised administration, it works. Without supervision, it largely does not. That single fact shapes everything about how this medication should be prescribed, monitored, and understood.

Unlike naltrexone, which reduces alcohol cravings by blocking opioid receptors, or acamprosate, which stabilizes glutamate signaling disrupted by chronic alcohol use, disulfiram operates through an entirely different principle: aversion [cite: mann-2004-pharmacotherapy-alcohol-dependence]. It does not reduce the desire to drink. It makes drinking physically punishing. And because the deterrent effect depends on the person knowing they have taken the medication, the behavioral and relational structure surrounding disulfiram is not a supplement to the treatment — it is the treatment itself.

This guide synthesizes the best available evidence on disulfiram's mechanism, clinical trial data, patient selection, safety profile, and real-world implementation. It is written for clinicians, people considering this medication, and anyone who wants an honest, evidence-grounded account of what disulfiram can and cannot do.

Mechanism — ALDH2 Inhibition

When a person drinks alcohol, the body breaks it down in two steps. First, alcohol (ethanol) is converted to acetaldehyde by the enzyme alcohol dehydrogenase. Second, acetaldehyde — a toxic compound — is rapidly converted to harmless acetate by aldehyde dehydrogenase 2 (ALDH2). Under normal circumstances, this second step happens quickly enough that acetaldehyde never accumulates to levels that cause symptoms [corpus-gap].

Disulfiram blocks that second step. It irreversibly inhibits ALDH2, meaning that if a person taking disulfiram consumes alcohol, acetaldehyde builds up in the bloodstream. The result is the disulfiram-ethanol reaction (DER): a cluster of intensely unpleasant and potentially dangerous symptoms that typically begin within 10 to 30 minutes of alcohol exposure.

Because disulfiram binds ALDH2 irreversibly, its effects persist long after the last dose. This extended duration of action is clinically important: patients who decide impulsively to drink after stopping disulfiram may still experience a reaction days later.

Disulfiram also inhibits dopamine beta-hydroxylase, the enzyme that converts dopamine to norepinephrine. This secondary mechanism is relevant to several of the medication's neurological side effects and psychiatric risks discussed later in this guide [cite: matasgarcía-2022-intranasal-disulfiram-induced].

Trial Evidence — Supervised vs. Unsupervised

The most important finding in the disulfiram literature is also the most frequently misunderstood: supervised disulfiram works; unsupervised disulfiram does not.

The clearest evidence comes from a 2014 meta-analysis by Skinner and colleagues, which analyzed 22 randomized controlled trials [cite: skinner-2014-disulfiram-efficacy-treatment]. Across all studies, disulfiram showed a meaningful overall effect size favoring it over controls [cite: skinner-2014-disulfiram-efficacy-treatment]. When the researchers separated open-label supervised trials from blinded trials, the picture became stark: supervised studies produced a significant effect size, while blinded studies showed no advantage over placebo [cite: skinner-2014-disulfiram-efficacy-treatment].

This is not a methodological inconvenience. It is the central clinical truth about how disulfiram works. The medication's deterrent effect requires the person to know they have taken it. A blinded patient — one who does not know whether they received disulfiram or placebo — has no reason to believe drinking will be punished, and the deterrence collapses entirely. Supervision is not an add-on to disulfiram therapy; it is the mechanism by which the therapy functions.

Real-world data reinforces this. A retrospective study by Diehl and colleagues of 353 patients found that supervised disulfiram outperformed acamprosate on every primary and secondary outcome: time to first relapse, attendance at outpatient treatment, and cumulative abstinence — all with Kaplan-Meier differences at p < 0.01 [cite: diehl-2010-why-disulfiram-superior]. What makes this finding especially striking is that the disulfiram group started from a worse position: they had longer duration of alcohol dependence, higher daily consumption, and more prior detoxifications than the acamprosate group. Despite these disadvantages, supervised disulfiram produced better outcomes.

More recent effectiveness data from Schallenberg and colleagues followed 45 severely affected outpatients treated between 2011 and 2023 [cite: schallenberg-2025-effectiveness-disulfiram-adjunct]. Fifty percent maintained abstinence for at least one year when disulfiram was combined with addiction-focused treatment — a meaningful result in a population with high rates of comorbidity.

The adherence problem, however, is real and documented. An open-label pilot by Bogenschutz and colleagues found that adherence to disulfiram declined steadily from 85.4% at four weeks to just 36.6% at sixteen weeks [cite: bogenschutz-2016-coadministration-disulfiram-lorazepam]. The same study found that duration of adherence strongly predicted abstinence at 16 weeks [cite: bogenschutz-2016-coadministration-disulfiram-lorazepam] — meaning dropout is not merely an attrition problem, it is a direct efficacy problem. The medication stops working the moment the person stops taking it, and most people stop taking it within a few months without structural support.

Patient Selection

Disulfiram is not a first-line medication for most people with AUD. Patient selection is everything.

Counterintuitively, the Diehl et al. data suggests that people with longer duration of alcohol dependence may actually do better with supervised disulfiram than with acamprosate — the opposite of what one might expect [cite: diehl-2010-why-disulfiram-superior]. This finding challenges the assumption that treatment-resistant or severely affected patients are poor candidates. For people who have tried other approaches and not succeeded, supervised disulfiram may be precisely the right fit.

The German NAP network, which tracked 1,579 treatment cases from 2019 to 2023 across 33 specialist centers, provides the most detailed real-world picture of who actually receives disulfiram [cite: zimmermann-2025-patient-quality-characteristics]. More than one quarter of patients had comorbid depression. Approximately 5% each had ADHD, borderline personality disorder, trauma-related disorders, and anxiety disorders. Thirty-three percent were receiving concurrent antidepressants, and 12% were on sedating antipsychotics. These are not the clean, uncomplicated patients of idealized clinical trials — they are the typical patients seen in addiction medicine practice.

A case series by Mutschler and colleagues specifically examined supervised disulfiram in patients with comorbid borderline personality disorder — a group often reflexively excluded due to concerns about impulsivity and suicide risk [cite: mutschler-2010-supervised-disulfiram-relapse]. Over a mean adherence period of 18.44 months, no serious adverse events and no suicidal behavior were reported. The supervision structure itself appeared to be the protective factor. This is preliminary evidence from a small case series (n=8) and should not be overgeneralized, but it challenges categorical exclusion based on personality disorder diagnosis alone.

For psychotic spectrum disorders, Petrakis and colleagues found that patients with schizophrenia, schizoaffective disorder, and bipolar disorder had worse alcohol outcomes overall, but still showed better outcomes on active medication versus placebo, with retention exceeding 80% [cite: petrakis-2006-psychotic-spectrum-disorders]. Disulfiram showed no clear advantage over naltrexone in this population, suggesting that for people with psychotic spectrum disorders, naltrexone may be a preferable choice — but psychosis is not an absolute contraindication.

The proposed mechanism — elevated dopamine resulting from disulfiram's inhibition of dopamine beta-hydroxylase — has direct implications for patients with bipolar disorder or stimulant use disorder, who warrant heightened caution and close monitoring.

An underappreciated selection consideration is bone health. Saha and colleagues documented a statistically significant reduction in lumbar spine bone mineral density (0.942 ± 0.105 vs. 0.924 ± 0.108 g/cm², p = 0.003) over a mean of 225 days of disulfiram therapy, with 41.7% of patients showing clinically meaningful bone mineral density loss at 12 months [cite: saha-2024-osteopenic-effect-disulfiram]. The beta-CTx/osteocalcin ratio also increased significantly (p = 0.033), suggesting increased bone resorption. Patients with pre-existing osteoporosis or elevated fracture risk warrant additional consideration before initiating disulfiram.

It is important to note that the evidence corpus does not document any systematic pre-prescribing screening protocol being applied in routine clinical practice [corpus-gap]. The underuse problem — only a small minority of Americans with AUD receive any pharmacotherapy [cite: zimmermann-2025-patient-quality-characteristics] — and the screening gap almost certainly coexist.

Supervised Administration Models

Because supervision is the mechanism by which disulfiram works, the structure of that supervision matters enormously in practice.

The Diehl et al. retrospective study used thrice-weekly appointments as the supervision model [cite: diehl-2010-why-disulfiram-superior]. The Mutschler case series used up to three brief physician contacts per week [cite: mutschler-2010-supervised-disulfiram-relapse]. The Bogenschutz pilot used monitored pharmacotherapy with adherence tracked over 16 weeks [cite: bogenschutz-2016-coadministration-disulfiram-lorazepam]. A study by De Sousa and colleagues used family member supervision to maintain compliance, achieving 90% abstinence at 9 months in the disulfiram group versus 56% for topiramate [cite: desousa-2008-open-randomized-trial] — a finding that highlights how family-supervised administration can function as a powerful structural mechanism.

The German NAP network data notes that 66% of patients received concomitant group therapy alongside disulfiram [cite: zimmermann-2025-patient-quality-characteristics], suggesting that in high-quality programs, disulfiram is rarely administered in isolation.

What the evidence corpus cannot tell us — and this is a genuine gap — is whether partner supervision, pharmacist-witnessed dispensing, clinic-based administration, or digital monitoring produce equivalent outcomes. Supervision is treated as a binary variable in the literature (present or absent), when in reality the quality, frequency, and relational character of supervision likely matter considerably. This is one of the most important unanswered questions in disulfiram implementation research.

Cardiac and Other Contraindications

The disulfiram-ethanol reaction is not merely uncomfortable — it can be life-threatening in vulnerable patients, and cardiac risk is the most serious concern.

A case report by Agarwal documents diffuse subendocardial ischemia following disulfiram-alcohol ingestion [corpus-gap]. Subendocardial ischemia represents hemodynamically significant myocardial compromise — a genuine cardiac emergency. While a single case report cannot establish incidence rates, it confirms that the DER can precipitate serious myocardial events.

The DER symptom profile — tachycardia, hypotension, flushing, palpitations, shortness of breath — represents a hemodynamic stress that a compromised heart may not tolerate. Patients with established coronary artery disease, recent myocardial infarction, cardiomyopathy, significant arrhythmia, or decompensated heart failure face elevated risk during any DER event. Uncontrolled hypertension is also a concern.

The German NAP network's reassuring safety data — reflecting a carefully selected, specialist-supervised population [cite: zimmermann-2025-patient-quality-characteristics] — cannot be generalized to routine prescribing in patients with significant cardiovascular disease, who may have been screened out of that cohort entirely.

Additional contraindications include:

• Psychosis history: Disulfiram-induced mania has been documented, and the dopaminergic mechanism warrants caution in patients with bipolar disorder or psychotic spectrum disorders [cite: petrakis-2006-psychotic-spectrum-disorders]
• Severe hepatic impairment: Disulfiram is hepatically metabolized, and pre-existing liver disease increases toxicity risk
• Pregnancy: Disulfiram is not recommended during pregnancy
• Pre-existing osteoporosis: Given the documented bone mineral density reduction [cite: saha-2024-osteopenic-effect-disulfiram]
• Neurological vulnerability: A case report by Matas-García and colleagues documents acute encephalopathy with bilateral pallidal necrosis following high-dose disulfiram, implicating dopamine beta-hydroxylase inhibition [cite: matasgarcía-2022-intranasal-disulfiram-induced]. The document notes that disulfiram neurotoxicity should be suspected during chronic therapy, not only in acute overdose

Drug Interactions

Disulfiram has several clinically significant drug interactions that require attention before prescribing and ongoing monitoring during treatment.

Metronidazole: Co-administration of disulfiram and metronidazole carries a risk of acute psychosis and confusional states. This combination should be avoided.

Isoniazid: Concurrent use with isoniazid has been associated with neurological toxicity, including psychosis. Patients being treated for tuberculosis require careful evaluation before disulfiram is considered.

Warfarin: Disulfiram potentiates the anticoagulant effect of warfarin, increasing bleeding risk. Patients on warfarin who begin disulfiram require more frequent INR monitoring and likely dose adjustment.

Phenytoin: Disulfiram inhibits phenytoin metabolism, potentially leading to phenytoin toxicity. Dose adjustment and monitoring are warranted.

It is important to note that the expert panel identified a meaningful gap in the evidence corpus: no document in the reviewed literature specifically addresses disulfiram's interactions with antidepressants or antipsychotics — despite the fact that 33% of patients in the German NAP network were receiving concurrent antidepressants and 12% were on sedating antipsychotics [cite: zimmermann-2025-patient-quality-characteristics]. Disulfiram inhibits CYP2E1 and may affect the metabolism of drugs processed through that pathway, but the clinical significance of these interactions in real-world AUD patients remains underdetermined by the current evidence base.

Alcohol-containing products: Patients must be counseled that the disulfiram-ethanol reaction can be triggered by any source of ethanol — not just beverages. Ghosh and colleagues documented that alcohol-based hand sanitizers triggered DER symptoms in adherent patients, including severe systemic reactions [cite: ghosh-2021-disulfiram-ethanol-reaction]. Patients should be advised to check the labels of mouthwashes, cough syrups, aftershaves, cooking wines, and other over-the-counter products that may contain alcohol.

The Disulfiram-Ethanol Reaction

The disulfiram reaction — the physiological response that occurs when a person taking disulfiram consumes alcohol — is the central mechanism of the medication's therapeutic effect and its primary safety concern.

Symptoms typically begin within 10 to 30 minutes of alcohol exposure and include flushing, sweating, nausea, vomiting, diarrhea, dizziness, tremors, palpitations, headache, and shortness of breath [cite: dem-2023-aversive-reaction-between]. In most patients, the reaction is intensely unpleasant but not dangerous.

Severity correlates with both the disulfiram dose and the amount of alcohol consumed [cite: ghosh-2021-disulfiram-ethanol-reaction]. The Ghosh et al. study found that even incidental alcohol exposure — from hand sanitizers — produced severe systemic reactions in some patients, with reaction severity associated with greater exposure amounts [cite: ghosh-2021-disulfiram-ethanol-reaction]. This underscores that cardiac risk during the DER is not confined to intentional drinking scenarios.

Patients who stop taking disulfiram must be explicitly counseled about this extended risk window.

Management of a severe DER is supportive: intravenous fluids for hypotension, antihistamines for flushing, and cardiac monitoring in patients with cardiovascular risk factors. Severe reactions warrant emergency evaluation.

Implant and Long-Acting Formulations

Disulfiram implants — subcutaneous pellets designed to provide sustained-release drug delivery over weeks to months — have been investigated as a way to address the adherence problem that undermines oral disulfiram's effectiveness. The appeal is straightforward: if a patient cannot simply stop taking the medication, the supervision requirement is partially built into the formulation itself.

However, the evidence for implant formulations is mixed, and no disulfiram implant is currently FDA-approved in the United States. Questions about consistent drug release, tissue reactions at the implant site, and whether implant-level blood concentrations reliably produce the DER have not been fully resolved in the available literature.

A separate formulation development worth noting: Ohta and colleagues studied an intranasal disulfiram formulation using a hydroxypropyl-β-cyclodextrin inclusion complex, finding that it produced anxiolytic effects at lower doses without triggering the alcohol-disulfiram interaction seen with oral administration in rats [cite: ohta-2025-intranasal-administration-disulfiram]. This is pharmacologically interesting for potential repurposing of disulfiram in anxiety or other conditions — but it would undermine the aversive deterrent mechanism that drives efficacy in AUD. Formulation choices are not neutral when the mechanism of action depends on the patient experiencing consequences for drinking.

Underutilization

Despite decades of evidence supporting supervised disulfiram's efficacy, the medication is prescribed to a small minority of people who might benefit from it. Available data suggest that only a small fraction of Americans with AUD receive any pharmacotherapy for the condition [cite: zimmermann-2025-patient-quality-characteristics], and medications are prescribed to fewer than 9% of patients likely to benefit across the broader literature [corpus-gap].

Several factors contribute to disulfiram's underuse specifically:

The supervision burden: Disulfiram without supervision is largely ineffective [cite: skinner-2014-disulfiram-efficacy-treatment], but building supervision into clinical workflows requires time, infrastructure, and often the involvement of family members or pharmacists. Many healthcare settings are not structured to support this.

Cardiac screening requirements: The DER's cardiovascular risks mean that prescribers must assess cardiac history before initiating disulfiram — a step that adds complexity and may deter prescribing in primary care settings where cardiac evaluation is not routine.

Prescriber unfamiliarity: Disulfiram's mechanism, contraindications, and drug interactions are not always well-understood outside addiction medicine specialty settings.

Side effect concerns: The documented side effect profile — including unpleasant body odor, fatigue, sexual dysfunction, and the emerging bone health signal [cite: saha-2024-osteopenic-effect-disulfiram] — may discourage both prescribers and patients [cite: zimmermann-2025-patient-quality-characteristics].

Stigma and framing: Aversion therapy carries a cultural weight that other pharmacotherapies do not. Some clinicians and patients find the punitive framing of disulfiram philosophically uncomfortable, even when the evidence supports its use in motivated patients.

The underuse problem and the screening gap almost certainly coexist: a system prescribing at such low rates is unlikely to be simultaneously over-screening for contraindications. Both problems need to be addressed.

Evidence Gaps

Honest clinical guidance requires acknowledging what the evidence cannot yet tell us. Several important questions remain unanswered by the current literature:

What happens after disulfiram is discontinued? The Bogenschutz data documents that adherence collapses from 85.4% at four weeks to 36.6% at sixteen weeks [cite: bogenschutz-2016-coadministration-disulfiram-lorazepam], and that duration of adherence strongly predicts abstinence [cite: bogenschutz-2016-coadministration-disulfiram-lorazepam]. However, no study in the reviewed literature systematically tracks what happens to patients after they stop — whether they relapse, transition to other pharmacotherapies, re-engage with treatment, or experience lasting benefit from their period of disulfiram-supported abstinence. Discontinuation is the modal outcome, and we are managing it blind.

What is the optimal supervised administration model? The evidence consistently shows that supervision drives efficacy [cite: skinner-2014-disulfiram-efficacy-treatment], but treats supervision as a binary variable. Whether partner supervision, pharmacist-witnessed dispensing, clinic-based administration, or digital monitoring produce equivalent outcomes has not been systematically studied. This is the translational bridge between efficacy evidence and real-world implementation.

What are the long-term outcomes of disulfiram treatment? The Schallenberg cohort provides one-year abstinence data [cite: schallenberg-2025-effectiveness-disulfiram-adjunct], and the Saha bone density study tracks outcomes over a mean of 225 days [cite: saha-2024-osteopenic-effect-disulfiram], but longer-term follow-up data is sparse.

How should bone health be monitored and managed? The finding that 41.7% of patients showed clinically meaningful bone mineral density loss at 12 months [cite: saha-2024-osteopenic-effect-disulfiram] is a significant safety signal without a corresponding management protocol in the literature.

What are the outcomes for women? The Skinner et al. meta-analysis included populations that were 89% male [cite: skinner-2014-disulfiram-efficacy-treatment]. Female-specific outcomes, pharmacokinetics, and safety data are substantially underrepresented in the disulfiram literature.

What are the clinically significant drug interactions with commonly co-prescribed medications?

What is the cardiovascular risk in patients with pre-existing heart disease? The corpus documents cardiac harm at the case level [corpus-gap] and population-level safety in supervised specialist settings [cite: zimmermann-2025-patient-quality-characteristics], but contains no prospective data on disulfiram outcomes specifically in patients with coronary artery disease, heart failure, or significant arrhythmia. Cardiac contraindication guidance currently rests on expert opinion and biological plausibility, not prospective evidence.

Summary

Disulfiram — Antabuse — is a medication with a clear mechanism, a well-characterized evidence base, and a specific clinical niche. Under supervised administration, it produces meaningful improvements in abstinence rates, even in patients who have not responded to other treatments. Without supervision, it does not work.

The evidence supports using disulfiram in highly motivated patients who have reliable accountability structures, no significant cardiovascular disease, and no psychiatric contraindications that would make the dopaminergic risks unacceptable. It is not a first-line medication for most people with AUD, but for the right patient with the right support, it can be a powerful tool.

The medication's underuse is a genuine problem — not because disulfiram should be prescribed more broadly, but because the patients who would benefit most from supervised disulfiram are often never offered it. Closing that gap requires not just prescriber education, but investment in the supervision infrastructure that makes the medication work: the clinical relationships, the accountability structures, and the ongoing monitoring that transform a tablet into a treatment.

Verified References

• ^[1] Agarwal, Rakesh (2022). "Diffuse subendocardial ischemia secondary to disulfiram-alcohol ingestion.". Indian J Pharmacol. DOI: 10.4103/ijp.ijp_930_21 [abstract-verified: partial]
• ^[2] Bogenschutz, Michael P, Bhatt, Snehal, Bohan, Juliane et al. (2016). "Coadministration of disulfiram and lorazepam in the treatment of alcohol dependence and co-occurring anxiety disorder: an open-label pilot study.". Am J Drug Alcohol Abuse. DOI: 10.3109/00952990.2016.1168430 [abstract-verified: yes]
• ^[3] Dem, Ugyen, Letho, Zimba, Dorji, Chencho et al. (2023). "Aversive Reaction Between Disulfiram and Betel Quid Among Inpatients With Alcohol Use Disorder in Bhutan: A Preliminary Study.". Asia Pac J Public Health. DOI: 10.1177/10105395231204801 [abstract-verified: partial]
• ^[4] De Sousa, Avinash Aaron, De Sousa, Jaya, Kapoor, Hema (2008). "An open randomized trial comparing disulfiram and topiramate in the treatment of alcohol dependence.". J Subst Abuse Treat. DOI: 10.1016/j.jsat.2007.05.012 [abstract-verified: yes]
• ^[5] Diehl, Alexander, Ulmer, Lisa, Mutschler, Jochen et al. (2010). "Why is disulfiram superior to acamprosate in the routine clinical setting? A retrospective long-term study in 353 alcohol-dependent patients.". Alcohol Alcohol. DOI: 10.1093/alcalc/agq017 [abstract-verified: yes]
• ^[6] Ghosh, Abhishek, Mahintamani, Tathagata, Balhara, Y P S et al. (2021). "Disulfiram Ethanol Reaction with Alcohol-Based Hand Sanitizer: An Exploratory Study.". Alcohol Alcohol. DOI: 10.1093/alcalc/agaa096 [abstract-verified: yes]
• ^[7] Lanz, Jenna, Biniaz-Harris, Nicholas, Kuvaldina, Mara et al. (2023). "Disulfiram: Mechanisms, Applications, and Challenges.". Antibiotics (Basel). DOI: 10.3390/antibiotics12030524 [abstract-verified: partial]
• ^[8] Mann, Karl (2004). "Pharmacotherapy of alcohol dependence: a review of the clinical data.". CNS Drugs. DOI: 10.2165/00023210-200418080-00002 [abstract-verified: partial]
• ^[9] Matas-García, A, Téllez, A, Fernández, S et al. (2022). "Intranasal disulfiram-induced encephalopathy: clinical and neuroimage findings.". Rev Neurol. DOI: 10.33588/rn.7511.2021415 [abstract-verified: partial]
• ^[10] Mutschler, Jochen, Grosshans, Martin, Koopmann, Anne et al. (2010). "Supervised disulfiram in relapse prevention in alcohol-dependent patients suffering from comorbid borderline personality disorder--a case series.". Alcohol Alcohol. DOI: 10.1093/alcalc/agq001 [abstract-verified: yes]
• ^[11] Ohta, Arisa, Terashima, Yuya, Matsuura, Kota et al. (2025). "Intranasal Administration of Disulfiram in Rats Produces Rapid and Potent Anxiolytic-Like Effects Without Adverse Alcohol-Related Interactions.". Adv Pharmacol Pharm Sci. DOI: 10.1155/adpp/5585693 [abstract-verified: yes]
• ^[12] Petrakis, Ismene L, Nich, Charla, Ralevski, Elizabeth (2006). "Psychotic spectrum disorders and alcohol abuse: a review of pharmacotherapeutic strategies and a report on the effectiveness of naltrexone and disulfiram.". Schizophr Bull. DOI: 10.1093/schbul/sbl010 [abstract-verified: yes]
• ^[13] Elisabeth Poorman, Brianna M McQuade, Sarah Messmer (2024). "Medications for Alcohol Use Disorder.". American family physician. [abstract-verified: yes]
• ^[14] Saha, Soma, Mittal, Monika, Goswami, Ravinder et al. (2024). "Osteopenic Effect of Disulfiram Therapy in Patients With Alcohol Use Disorder.". Cureus. DOI: 10.7759/cureus.73643 [abstract-verified: yes]
• ^[13] Schallenberg, Max, Vogel-Blaschka, Diana, Spreer, Maik et al. (2025). "Effectiveness of Disulfiram as Adjunct to Addiction-Focused Treatment for Persons With Severe Alcohol Use Disorder.". Addict Biol. DOI: 10.1111/adb.70035 [abstract-verified: partial]
• ^[7] Skinner, Marilyn D, Lahmek, Pierre, Pham, Héloïse et al. (2014). "Disulfiram efficacy in the treatment of alcohol dependence: a meta-analysis.". PLoS One. DOI: 10.1371/journal.pone.0087366 [abstract-verified: partial]
• ^[15] Zimmermann, Ulrich S, Plickert, Clemens, Lüdecke, Christel et al. (2025). "[Patient and quality characteristics in the treatment with disulfiram (Antabus) in the German "Network for Alcohol Aversive Pharmacotherapy"].". Nervenarzt. DOI: 10.1007/s00115-024-01714-5 [abstract-verified: partial]

Replacement Resolution Audit

Each REPLACE verdict from the adjudication pass was resolved by re-querying the indexed fulltext corpus and selecting the highest-scoring paper that the Level 3 verifier confirmed supports the claim.

• ^[16] → ^[17] (verifier: partial; score 0.84). Title: Disulfiram efficacy in the treatment of alcohol dependence: a meta-analysis.
• ^[16] → ^[17] (verifier: partial; score 0.64). Title: Disulfiram efficacy in the treatment of alcohol dependence: a meta-analysis.
• ^[18] → ^[13] (verifier: partial; score 0.76). Title: Effectiveness of Disulfiram as Adjunct to Addiction-Focused Treatment for Persons With Severe Alcohol Use Disorder.
• ^[19] → ^[15] (verifier: partial; score 0.62). Title: Efficacy of disulfiram and Twelve Step Facilitation in cocaine-dependent individuals maintained on methadone: a randomiz
• ^[20] → NO REPLACEMENT FOUND (considered 4 candidates; none verified)
• [gonzálezromero-2024-aversive-induced-mania] → ^[21] (verifier: partial; score 0.69). Title: Disulfiram resistance in alcohol dependence: Myth or reality?
• [gonzálezromero-2024-aversive-induced-mania] → ^[16] (verifier: partial; score 0.68). Title: Disulfiram: Mechanisms, Applications, and Challenges.
• ^[16] → ^[22] (verifier: partial; score 0.58). Title: A Comprehensive Review on Alcohol Abuse Disorder Fatality, from Alcohol Binges to Alcoholic Cardiomyopathy.
• [matasgarcía-2022-intranasal-disulfiram-induced] → ^[9] (verifier: partial; score 0.79). Title: Practical outpatient pharmacotherapy for alcohol use disorder.
• [matasgarcía-2022-intranasal-disulfiram-induced] → NO REPLACEMENT FOUND (considered 4 candidates; none verified)
• ^[17] → ^[7] (verifier: partial; score 0.61). Title: Pharmacological Treatment of Alcohol use Disorder in Patients with Psychotic Disorders: A Systematic Review.
• ^[13] → NO REPLACEMENT FOUND (considered 4 candidates; none verified)
• ^[19] → ^[13] (verifier: partial; score 0.65). Title: Effectiveness of Disulfiram as Adjunct to Addiction-Focused Treatment for Persons With Severe Alcohol Use Disorder.
• ^[19] → ^[23] (verifier: partial; score 0.81). Title: A Novel ALDH2 Inhibitor for the Treatment of Alcohol Use Disorder: Preclinical Findings.
• ^[19] → ^[17] (verifier: partial; score 0.66). Title: Disulfiram efficacy in the treatment of alcohol dependence: a meta-analysis.
• ^[20] → ^[1] (verifier: partial; score 0.75). Title: Repurposing Disulfiram as an Antimicrobial Agent in Topical Infections.
• ^[24] → ^[6] (verifier: partial; score 0.73). Title: Disulfiram and cancer immunotherapy: Advanced nano-delivery systems and potential therapeutic strategies.
• ^[25] → ^[3] (verifier: partial; score 0.76). Title: Pharmacotherapy for alcohol dependence: anticraving medications for relapse prevention.