Topiramate for Alcohol Use Disorder: A Comprehensive Clinical Review

Overview

Topiramate is one of the most thoroughly studied off-label medications for alcohol use disorder (AUD). It is not approved by the FDA for this purpose — that is a regulatory status, not a statement about the evidence. The evidence is, in fact, substantial. Multiple randomized controlled trials (RCTs) and meta-analyses consistently show that topiramate reduces heavy drinking days, lowers alcohol craving, and in at least one well-powered head-to-head trial, performed at least as well as naltrexone — a first-line FDA-approved option — on several key outcomes ^[1].

The central tension in topiramate's story is not whether it works. The evidence that it works is strong. The tension is between a compelling efficacy profile and a side effect burden that creates real adherence challenges — and between robust trial data and a clinical culture that has been slow to adopt an off-label agent when FDA-approved alternatives exist.

This article synthesizes findings from a multi-expert panel discussion grounded in verified research documents. It is designed to give clinicians, patients, and caregivers an honest, evidence-based picture of what topiramate can and cannot do for people living with AUD.

Mechanism of Action

Topiramate works through two complementary pathways that directly target the neurochemistry of alcohol dependence.

First, it enhances the activity of gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter. Alcohol artificially boosts GABA activity, producing its sedating and rewarding effects. Over time, the brain compensates by downregulating its own GABA system — which is part of why stopping alcohol causes anxiety, agitation, and withdrawal. Topiramate helps restore inhibitory tone.

Second, it blocks AMPA and kainate receptors, which are subtypes of glutamate receptors. Glutamate is the brain's primary excitatory neurotransmitter. Chronic alcohol use sensitizes the glutamate system, contributing to craving, compulsive drinking, and the hyperexcitability of withdrawal. By antagonizing these receptors, topiramate dampens the excitatory drive that fuels alcohol-seeking behavior.

Together, these two actions — more inhibition, less excitation — are thought to target the mesocorticolimbic dopamine system, the brain's reward circuitry where alcohol's reinforcing effects are processed. Behavioral economic research supports this mechanism: topiramate has been shown to reduce alcohol's reinforcing value ^[2], and neuroimaging studies demonstrate that it attenuates cue-elicited neural activation ^[3]. In plain terms, topiramate appears to make alcohol less rewarding and less compelling — which is exactly the target for a medication treating AUD.

Trial Evidence

Foundational RCTs

The evidence base for topiramate in AUD includes two landmark trials led by Johnson and colleagues. In the 2003 trial, participants receiving topiramate up to 300 mg/day reported 2.88 fewer drinks per day and a 27.6% reduction in heavy drinking days compared to placebo ^[4]. These were clinically meaningful differences, not just statistically significant ones ^[4].

Meta-Analytic Evidence

Multiple meta-analyses anchor the current evidence base.

Blodgett et al. analyzed seven RCTs and found small-to-moderate effects favoring topiramate across multiple outcomes: abstinence (Hedges' g = 0.468), heavy drinking (g = 0.406), gamma-glutamyl transferase or GGT — a liver enzyme that rises with heavy alcohol use (g = 0.324), and craving (g = 0.312) ^[5]. These effect sizes are comparable to those seen with FDA-approved AUD medications.

A Bayesian meta-analysis by Fluyau et al. confirmed and extended these findings ^[6]. Topiramate reduced heavy drinking days (Cohen's d = 0.401, Bayes Factor = 23.088), alcohol craving (d = 0.477, BF = 107.749), and prolonged abstinence (d = 0.505, BF = 54.998) ^[6]. Bayes factors above 10 are generally considered strong evidence; a BF of 107 for craving reduction means the data are more than 100 times more likely under the hypothesis that topiramate works than under the hypothesis that it does not. This is not a marginal finding ^[6].

An earlier meta-analysis reported that topiramate significantly reduced heavy drinking days (SMD = −0.77, 95% CI: −1.12 to −0.42) and increased abstinent days (mean difference: 2.9 days, 95% CI: 2.5 to 3.3) compared to placebo ^[7].

A network meta-analysis by Palpacuer et al. — which compared multiple AUD pharmacotherapies simultaneously — found topiramate superior to naltrexone, acamprosate, and nalmefene on total alcohol consumption (SMD = −0.77 vs. placebo) ^[8] (Note: this specific figure could not be independently verified against the source abstract — the underlying study supports the general finding but the exact number should be confirmed before publication). Across these analyses, topiramate consistently performed favorably relative to major approved comparators on this outcome ^[8].

Head-to-Head Comparison with Naltrexone

The most clinically actionable recent trial is the 2024 genotype-stratified RCT by Morley et al. — the first well-powered direct comparison of topiramate and naltrexone. Topiramate was at least as effective as naltrexone for heavy drinking days, and superior for drinks per drinking day, BMI, craving, and GGT reduction ^[1]. Withdrawal due to side effects was 8% for topiramate versus 5% for naltrexone ^[1] — a modest difference, though one that matters for real-world adherence.

That an off-label agent outperforms a guideline-recommended first-line treatment on multiple clinically meaningful outcomes, yet remains marginalized in practice, is one of the central paradoxes this evidence base documents ^[1].

Real-World Signal

An EHR-based observational study found that topiramate prescriptions — even when written for other indications such as migraine — were associated with modest reductions in AUDIT-C scores, particularly at doses above 150 mg/day ^[9]. This real-world signal, while modest, suggests topiramate's effects on drinking may not be confined to the controlled trial environment ^[9].

Topiramate for PTSD-AUD Comorbidity — The Norman 2025 Finding

People with post-traumatic stress disorder (PTSD) have significantly elevated rates of AUD, and treating both conditions simultaneously is a major clinical challenge. The Norman 2025 RCT addressed this directly — and produced findings that are both encouraging and clinically sobering.

What the Trial Did

One hundred veterans with comorbid PTSD and AUD were randomized to receive either Prolonged Exposure therapy plus topiramate (titrated to 250 mg/day over approximately 8 weeks) or Prolonged Exposure plus placebo ^[10]. Prolonged Exposure (PE) is an evidence-based trauma-focused psychotherapy.

What the Trial Found — The Dissociation

Topiramate improved PTSD symptoms. The PE+topiramate arm showed greater PTSD symptom reduction at post-treatment, including higher rates of PTSD diagnosis loss and clinically meaningful symptom change ^[10].

Topiramate did NOT significantly reduce heavy drinking days. This is the clinically consequential finding. Despite the robust evidence for topiramate's effects on drinking in other populations, the PE+topiramate arm did not show a significant advantage over PE+placebo on percent heavy drinking days ^[10].

This dissociation — PTSD benefit without differential alcohol benefit — is not a minor footnote. It challenges the assumption that treating PTSD symptoms will automatically reduce drinking, and it raises the possibility that in PTSD-comorbid AUD, the mechanisms driving heavy drinking may be partially independent of negative affect and trauma symptoms.

Session-Level Insights

A session-level analysis by Klein et al. added important nuance. PTSD symptom improvements in the topiramate arm began diverging from placebo at session 9, while alcohol craving differences emerged earlier, at session 6 (b = −3.10, SE = 1.33, p = .02) ^[11]. Exploratory cross-lagged analyses suggested that craving reductions may have driven subsequent PTSD improvements — meaning topiramate's effect on PTSD may have been mediated through its earlier effect on craving. This temporal sequencing has meaningful mechanistic implications, though it requires replication before firm conclusions can be drawn.

The Durability Problem

Critically, topiramate's PTSD advantage was not maintained at 3- or 6-month follow-ups after medication was discontinued ^[10]. This mirrors findings from Kranzler et al., who showed that topiramate's robust in-treatment effects on alcohol outcomes diminished substantially post-discontinuation ^[12]. The authors of Norman 2025 themselves suggest that "extending time on topiramate or additional strategies to prolong such effects may be useful" ^[10].

Clinical Implication

For people with PTSD-comorbid AUD, topiramate combined with trauma-focused therapy may accelerate PTSD recovery during active treatment. However, the lack of differential alcohol benefit means that for patients whose primary treatment goal is reducing heavy drinking, topiramate alone — even when combined with PE — may not be sufficient. Additional targeted AUD interventions may be needed. The benefit is real; it is simply more specific than initially hoped.

Dose Titration

Start low. Go slow. This is not a cliché — it is the pharmacological reality of topiramate.

The standard approach is to begin at 25 mg/day and increase by 25–50 mg per week, targeting a dose of 200–300 mg/day in divided doses ^[4]. The Johnson 2003 trial used an escalating schedule from 25 mg to 300 mg/day over 12 weeks ^[4].

Why does titration speed matter? Because most of topiramate's side effects — particularly cognitive dulling and paresthesias — are dose-dependent and most pronounced when doses rise quickly. Martinotti et al. specifically examined low-dose topiramate (100 mg/day, titrated over 2 weeks) and found efficacy with improved tolerability ^[13], suggesting that lower target doses may be a viable strategy for patients who cannot tolerate higher doses — though whether 100 mg represents fully adequate therapeutic dosing remains an open question.

The session-level data from Klein et al. suggest that clinical benefits on craving and PTSD symptoms emerge around sessions 6–9, which corresponds to the period when patients are approaching or reaching their target dose ^[11]. This means the titration period is not just a pharmacological formality — it is the window during which patients are most vulnerable to dropout before they have experienced meaningful benefit.

Robinson et al. used a 5-week titration to 125 or 250 mg/day and reported high attrition as a primary limitation, explicitly noting that poor medication adherence likely explains why primary outcomes were null despite exploratory analyses at 250 mg showing meaningful reductions in heavy drinking days ^[14]. This is a critical real-world signal: the medication that works in per-protocol analyses can fail in intent-to-treat analyses because patients do not stay on it long enough to reach therapeutic doses.

Practical guidance: Slower titration protects tolerability. If a patient experiences significant side effects at a given dose, it is reasonable to hold at that dose rather than continuing to escalate. Maintenance doses lower than the 200–300 mg target may still provide meaningful benefit for some patients.

Side Effects

Topiramate's side effect profile is the primary barrier to its broader use. These effects are real, they affect adherence, and patients deserve honest counseling about them before starting treatment.

Paresthesias

Tingling or numbness — most commonly in the hands, feet, and face — is the most frequently reported side effect. It is caused by topiramate's carbonic anhydrase inhibition and is generally benign, though it can be bothersome enough to prompt discontinuation. Patients should be told to expect this and reassured that it often diminishes over time.

Cognitive Dulling ("Dopamax")

The informal nickname "Dopamax" reflects a real clinical concern: word-finding difficulty, slowed thinking, and impaired concentration. This is the side effect most commonly cited by prescribers as a reason to avoid topiramate.

The evidence here is more nuanced than the reputation suggests. Hicks et al.'s 2026 RCT — conducted in veterans with PTSD and AUD receiving topiramate alongside Prolonged Exposure therapy — found no statistically significant differences between topiramate and placebo groups in verbal learning, memory, or processing speed, with all scores remaining within normal clinical ranges ^[15]. This is reassuring.

However, Pennington et al. found that topiramate did transiently impair verbal fluency and working memory in veterans with traumatic brain injury (TBI) and AUD ^[16]. This suggests that cognitive vulnerability — particularly in people with neurological comorbidities — is a real consideration. The concern is not entirely unfounded; it is population-specific.

The honest clinical message: cognitive side effects are real in some patients, particularly those with pre-existing neurological vulnerability, but may be less severe than commonly feared in neurologically intact individuals.

Weight Loss

Topiramate consistently produces weight loss, which can be a benefit for patients with obesity or metabolic syndrome, and a concern for patients who are already underweight. This effect contributed to topiramate's inclusion in the FDA-approved weight loss combination medication (topiramate/phentermine), though that approval does not extend to topiramate alone for AUD.

Kidney Stones

Topiramate increases the risk of nephrolithiasis (kidney stones) approximately 3–4 times above baseline, again through carbonic anhydrase inhibition, which reduces urinary citrate and raises urinary pH. Patients should be counseled to maintain adequate hydration. Those with a history of kidney stones require careful risk-benefit discussion before initiating topiramate.

Acute Angle-Closure Glaucoma

This is rare but serious. Topiramate can cause acute myopia and secondary angle-closure glaucoma, typically within the first month of treatment. Patients should be instructed to seek immediate evaluation for any sudden vision changes or eye pain. This is a contraindication to continued use if it occurs.

Metabolic Acidosis

Topiramate inhibits carbonic anhydrase in the kidney, which can reduce bicarbonate levels and cause a non-anion-gap metabolic acidosis. This is generally mild but can be clinically significant in patients with pre-existing acid-base disorders or those taking other medications that affect acid-base balance.

Contraindications and Cautions

Pregnancy. Topiramate carries a Category D pregnancy designation. It is associated with an increased risk of oral clefts (cleft lip and/or palate) in infants exposed during the first trimester. Women of childbearing potential should use effective contraception — with the important caveat that topiramate reduces the efficacy of oral contraceptives at higher doses (see Drug Interactions). This is a serious concern that requires explicit counseling.

History of kidney stones. Given topiramate's 3–4-fold increase in nephrolithiasis risk, a personal or family history of kidney stones warrants careful consideration and discussion.

Glaucoma. Pre-existing glaucoma, particularly angle-closure glaucoma, is a contraindication.

Severe hepatic impairment. Topiramate is partially metabolized by the liver; severe hepatic impairment may increase drug exposure.

Hypersensitivity. Topiramate is a sulfamate-substituted monosaccharide. Patients with known hypersensitivity to topiramate or sulfa-containing compounds should not use it.

Drug Interactions

Oral contraceptives. At doses of 200 mg/day and above, topiramate can significantly reduce plasma levels of estrogen in combined oral contraceptives, potentially reducing contraceptive efficacy. Patients should be counseled to use additional or alternative contraception.

CNS depressants. Topiramate has additive CNS depressant effects when combined with alcohol, benzodiazepines, opioids, or other sedating medications. This is particularly relevant in AUD, where patients may be using alcohol concurrently during early treatment.

Carbonic anhydrase inhibitors. Combining topiramate with other carbonic anhydrase inhibitors (such as acetazolamide or zonisamide) increases the risk of kidney stones and metabolic acidosis.

Antiepileptic drugs. Phenytoin and carbamazepine are enzyme inducers that can reduce topiramate plasma levels, potentially reducing efficacy. Conversely, topiramate can increase phenytoin levels.

When to Choose Topiramate

Topiramate is not a first-line agent by regulatory default, but the evidence supports its use in several clinical scenarios:

Patients who have not responded to naltrexone or acamprosate. Given topiramate's distinct mechanism of action — GABA potentiation and glutamate antagonism, rather than opioid receptor blockade or NMDA modulation — it may work for patients who did not benefit from approved agents.

Patients with comorbid migraine. Topiramate is FDA-approved for migraine prophylaxis. For a patient with both AUD and migraine, topiramate offers the opportunity to address both conditions with a single medication. The corpus does not contain direct data on this population, but the clinical logic is sound.

Patients with comorbid PTSD. The Norman 2025 data support topiramate's use in PTSD-AUD comorbidity for PTSD symptom reduction when combined with trauma-focused therapy ^[10]. Clinicians should be transparent with patients that the evidence for differential alcohol reduction in this population is less robust, and that additional AUD-focused interventions may be needed.

Patients with craving characterized by obsession and automaticity. Guglielmo et al. identify this craving phenotype — characterized by intrusive thoughts about drinking and automatic, habitual drinking behavior — as one where topiramate shows particular benefit ^[17]. This is clinically actionable, though not yet validated in a prospective subgroup trial.

Patients with obesity or metabolic syndrome. Topiramate's consistent weight loss effect may be an additional benefit in this population.

Patients who understand and accept the side effect profile. Shared decision-making is essential. Patients who are well-informed about what to expect — and who are motivated to work through the titration period — are better positioned to benefit.

Real-World Underutilization

Despite a compelling evidence base, topiramate remains largely off-label, underutilized, and absent from most first-line AUD treatment guidelines. The corpus documents this gap, though it cannot fully explain it.

The most clearly documented barrier is the side effect profile. Palpacuer et al.'s network meta-analysis explicitly states that topiramate's "safety profile is known to be poor" despite its superior efficacy on total alcohol consumption ^[8]. Withdrawal due to side effects in the Morley 2024 head-to-head trial was 8% for topiramate versus 5% for naltrexone ^[1] — a real but modest difference that does not fully account for the degree of clinical avoidance.

The cognitive concern, while real in some populations, appears to be overstated as a general barrier. The Hicks 2026 data showing no clinically significant cognitive impairment in a veteran population receiving topiramate alongside intensive psychotherapy ^[15] have not yet shifted prescriber behavior in proportion to their reassuring findings.

The durability problem is a legitimate concern. Topiramate's benefits during treatment diminish substantially after discontinuation ^{[12] [10]}. This raises real questions about optimal treatment duration that the current evidence base cannot answer — and may reasonably make clinicians hesitant to initiate a medication whose long-term management strategy is unclear.

Off-label status itself creates structural barriers. Without FDA approval for AUD, topiramate falls outside most guideline-recommended first-line options and may face formulary coverage challenges. Prescribers operating under quality-measure constraints or liability concerns may default to approved agents even when the evidence for topiramate is comparable or superior.

The corpus is almost entirely silent on implementation science — there are no prescriber survey data, no formulary access studies, no pragmatic trials in primary care settings. The Kranzler EHR study touches real-world use but focuses on drinking outcomes rather than prescribing patterns ^[9]. This silence is itself informative: the field has invested heavily in demonstrating that topiramate works, and very little in understanding why it is not being used.

Patient counseling before initiation is essential. Patients who are surprised by paresthesias or cognitive slowing are more likely to discontinue. Patients who have been told what to expect, and who understand that these effects are often dose-dependent and manageable, are better equipped to persist through the titration period and reach therapeutic benefit.

Evidence Gaps

The panel identified several areas where the current evidence base is insufficient to guide clinical decision-making:

Optimal dose. Robinson et al. found exploratory evidence that 250 mg/day reduced heavy drinking more than lower doses, though primary analyses were null due to high attrition ^[14]. The dose-response relationship is not well characterized, and the optimal target dose for different patient populations remains unclear ^[14].

Long-term outcomes. Most trials extend to 12–18 weeks ^[12]. The corpus does not adequately address what happens to patients who remain on topiramate for one, two, or more years — or what the optimal duration of treatment is before a discontinuation attempt.

Combination with naltrexone. There is limited head-to-head data and essentially no data on combination pharmacotherapy. Whether topiramate and naltrexone together offer additive benefit — given their distinct mechanisms — is an unanswered question.

Subgroup responders. The pharmacogenomic story is currently inconclusive. The GRIK1 rs2832407 polymorphism showed initial promise as a topiramate-specific biomarker, but failed to replicate in a prospective trial ^[18] and was non-significant in a combined analysis (partial η² = 0.026, p = 0.37) ^[19]. Morley et al. similarly found no significant moderation by rs2832407 or OPRM1 rs1799971 ^[1]. Precision medicine for topiramate in AUD is not yet viable based on current evidence.

Sex-disaggregated outcomes. The Norman 2025 trial was 84% male ^[10]. The generalizability of PTSD-AUD findings to women and non-binary individuals is unknown.

Discontinuation strategies. Given the documented loss of benefit after stopping topiramate ^[12], structured tapering protocols and strategies to preserve post-treatment gains are urgently needed but absent from the current literature.

Implementation science. The efficacy case is made. The implementation science is absent. Comparative research examining how off-label status, safety signals, and structural barriers translate into measurable differences in prescribing rates and equity of access across health systems is the next frontier for this evidence base ^[9].

Summary

Topiramate is an off-label but well-evidenced treatment for AUD. Its dual mechanism — GABA potentiation and glutamate antagonism — directly targets the neurochemistry of alcohol dependence. Meta-analyses consistently show small-to-moderate effect sizes for heavy drinking day reduction, craving, and abstinence ^{[5] [6]}. In the most rigorous head-to-head trial to date, it performed at least as well as naltrexone and better on several secondary outcomes ^[1].

For people with comorbid PTSD, topiramate combined with Prolonged Exposure therapy accelerates PTSD symptom recovery during active treatment — but does not significantly reduce heavy drinking days compared to PE alone, and benefits do not persist after discontinuation ^[10]. This is a clinically important nuance, not a reason to avoid topiramate in this population, but a reason to set realistic expectations and plan for additional AUD-focused support.

The side effect profile — paresthesias, cognitive dulling, weight loss, kidney stones, glaucoma — is real and requires honest pre-treatment counseling. Slow titration starting at 25 mg/day, with gradual increases to a target of 200–300 mg/day, minimizes these effects and gives patients the best chance of reaching therapeutic benefit ^[4].

Topiramate is not a breakthrough. It is not "just off-label." It is a medication with a substantial evidence base, meaningful clinical utility in select patients, and a side effect profile that demands careful patient selection and counseling. For the right patient — particularly one who has not responded to approved agents, who has comorbid migraine or PTSD, or whose craving pattern fits the obsessive-automatic phenotype — topiramate deserves serious consideration.

This article is intended for educational purposes and does not constitute individualized medical advice. Prescribing decisions should be made in consultation with a qualified healthcare provider familiar with the patient's full clinical history.

Verified References

• ^[7] Arbaizar, B, Diersen-Sotos, T, Gómez-Acebo, I et al. (2010). "Topiramate in the treatment of alcohol dependence: a meta-analysis.". Actas Esp Psiquiatr. [abstract-verified: partial]
• ^[5] Blodgett, Janet C, Del Re, A C, Maisel, Natalya C et al. (2014). "A meta-analysis of topiramate's effects for individuals with alcohol use disorders.". Alcohol Clin Exp Res. DOI: 10.1111/acer.12411 [abstract-verified: partial]
• ^[6] Fluyau, Dimy, Kailasam, Vasanth Kattalai, Pierre, Christopher G (2023). "A Bayesian meta-analysis of topiramate's effectiveness for individuals with alcohol use disorder.". J Psychopharmacol. DOI: 10.1177/02698811221149643 [abstract-verified: yes]
• ^[2] Goodyear, Kimberly, Miranda, Robert, MacKillop, James (2022). "Behavioral economic analysis of topiramate pharmacotherapy for alcohol: a placebo-controlled investigation of effects on alcohol reinforcing value and delayed reward discounting.". Psychopharmacology (Berl). DOI: 10.1007/s00213-021-06034-z [abstract-verified: partial]
• ^[17] Guglielmo, Riccardo, Martinotti, Giovanni, Quatrale, Marianna et al. (2015). "Topiramate in Alcohol Use Disorders: Review and Update.". CNS Drugs. DOI: 10.1007/s40263-015-0244-0 [abstract-verified: yes]
• ^[15] Hicks, Terrell A, Dell, Kristine C, Klein, Alexandra B et al. (2026). "Evaluating cognitive effects of topiramate in trauma-focused treatment: Findings from a randomized double-blind clinical trial of veterans with PTSD and alcohol use disorder.". Psychol Trauma. DOI: 10.1037/tra0002159 [abstract-verified: partial]
• ^[4] Johnson, Bankole A, Ait-Daoud, Nassima, Bowden, Charles L et al. (2003). "Oral topiramate for treatment of alcohol dependence: a randomised controlled trial.". Lancet. DOI: 10.1016/s0140-6736(03)13370-3 [abstract-verified: yes]
• ^[11] Klein, Alexandra B, Denk, Annie-Lori Joseph, Kline, Alexander C et al. (2026). "Session-level effects of prolonged exposure therapy with and without topiramate in veterans with posttraumatic stress disorder and alcohol use disorder.". Behav Res Ther. DOI: 10.1016/j.brat.2026.105036 [abstract-verified: partial]
• ^[19] Kranzler, Henry R, Hartwell, Emily E, Feinn, Richard et al. (2021). "Combined analysis of the moderating effect of a GRIK1 polymorphism on the effects of topiramate for treating alcohol use disorder.". Drug Alcohol Depend. DOI: 10.1016/j.drugalcdep.2021.108762 [abstract-verified: partial]
• ^[18] Kranzler, Henry R, Morris, Paige E, Pond, Timothy et al. (2021). "Prospective randomized pharmacogenetic study of topiramate for treating alcohol use disorder.". Neuropsychopharmacology. DOI: 10.1038/s41386-020-00945-9 [abstract-verified: partial]
• ^[9] Kranzler, Henry R, Leong, Shirley H, Naps, Michelle et al. (2022). "Association of topiramate prescribed for any indication with reduced alcohol consumption in electronic health record data.". Addiction. DOI: 10.1111/add.15980 [abstract-verified: partial]
• ^[12] Kranzler, Henry R, Feinn, Richard, Pond, Timothy et al. (2022). "Post-treatment effects of topiramate on alcohol-related outcomes: A combined analysis of two placebo-controlled trials.". Addict Biol. DOI: 10.1111/adb.13130 [abstract-verified: yes]
• ^[13] Martinotti, Giovanni, Di Nicola, Marco, De Vita, Ofelia et al. (2014). "Low-dose topiramate in alcohol dependence: a single-blind, placebo-controlled study.". J Clin Psychopharmacol. DOI: 10.1097/jcp.0000000000000228 [abstract-verified: yes]
• ^[1] Kirsten C Morley, Henry R Kranzler, Natasha Luquin et al. (2024). "Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial.". The American journal of psychiatry. DOI: 10.1176/appi.ajp.20230666 [abstract-verified: yes]
• ^[10] Sonya B Norman, Matthew T Luciano, Kaitlyn E Panza et al. (2025). "A Randomized Clinical Trial of Prolonged Exposure Therapy With and Without Topiramate for Comorbid PTSD and Alcohol Use Disorder.". The American journal of psychiatry. DOI: 10.1176/appi.ajp.20240470 [abstract-verified: partial]
• ^[8] Palpacuer, Clément, Duprez, Renan, Huneau, Alexandre et al. (2018). "Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta-analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate.". Addiction. DOI: 10.1111/add.13974 [abstract-verified: yes]
• ^[16] Pennington, David L, Bielenberg, Jennifer, Lasher, Brooke et al. (2020). "A randomized pilot trial of topiramate for alcohol use disorder in veterans with traumatic brain injury: Effects on alcohol use, cognition, and post-concussive symptoms.". Drug Alcohol Depend. DOI: 10.1016/j.drugalcdep.2020.108149 [abstract-verified: yes]
• ^[14] Robinson, Jason D, Anthenelli, Robert M, Cinciripini, Paul M et al. (2025). "High- and low-dose topiramate for the treatment of persons with alcohol use disorder who smoke cigarettes: A randomized control trial.". Alcohol Clin Exp Res (Hoboken). DOI: 10.1111/acer.70193 [abstract-verified: partial]
• ^[3] Wetherill, Reagan R, Spilka, Nathaniel, Jagannathan, Kanchana et al. (2021). "Effects of topiramate on neural responses to alcohol cues in treatment-seeking individuals with alcohol use disorder: preliminary findings from a randomized, placebo-controlled trial.". Neuropsychopharmacology. DOI: 10.1038/s41386-021-00968-w [abstract-verified: yes]

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.

• ^[11] → NO REPLACEMENT FOUND (considered 3 candidates; none verified)
• ^[2] → ^[2] (restored to correct corpus key; replaces erroneous ^[20])
• ^[5] → NO REPLACEMENT FOUND (considered 3 candidates; none verified)
• ^[7] → NO REPLACEMENT FOUND (considered 4 candidates; none verified)
• ^[9] → ^[9] (restored to correct corpus key; replaces erroneous ^[21])
• ^[10] → ^[10] (restored to correct corpus key; replaces erroneous ^[22])
• ^[15] → ^[15] (restored to correct corpus key; replaces erroneous ^[23])
• ^[18] → ^[18] (restored to correct corpus key; replaces erroneous ^[24])