Medication for Gambling Disorder: Evidence, Naltrexone, and Safety

Can medication treat gambling disorder?

Medication can be considered for some adults with gambling disorder, especially when an adequate course of gambling-specific psychological treatment has produced insufficient improvement or repeated relapse. Among drugs studied, the opioid-receptor antagonists naltrexone and nalmefene have the most promising controlled-trial evidence. The evidence remains limited in size, duration, and applicability to people with complex psychiatric or medical conditions. Naltrexone requires individualized specialist prescribing and medical monitoring, and its use for gambling disorder is off-label in the United States and the United Kingdom. NICE (2025); Dowling et al. (2022); Ioannidis et al. (2025).

The clinical decision concerns a person's gambling symptoms, functioning, safety, treatment preferences, and other diagnoses. Pharmacotherapy is one component of a plan that can include cognitive behavioral therapy (CBT), motivational interventions, measures that reduce gambling access, support with financial and relationship harms, and relapse prevention. NICE recommends offering gambling-specific CBT and considers naltrexone in defined circumstances after psychological treatment. Its recommendation is conditional and requires specialist oversight. NICE (2025).

What gambling disorder is and what medication is meant to change

Gambling disorder is a recognized behavioral addiction involving persistent or recurrent gambling behavior marked by impaired control, increasing priority given to gambling, and continuation or escalation despite damaging consequences. Financial losses, secrecy, debt, disrupted work, family conflict, anxiety, and serious psychological distress can occur. A person can also experience significant gambling-related harm without meeting the full threshold for a diagnosis. Diagnosis requires clinical assessment rather than a questionnaire score or an estimate of how much money has been lost. World Health Organization (2024); NICE (2025).

Medication research has usually focused on outcomes such as gambling urges, gambling symptom severity, time or money spent gambling, treatment response, and functioning. These outcomes overlap but are distinct. A reduction in urge intensity may support recovery while debt or damaged trust persists; an improvement on a gambling severity scale need not mean stable abstinence; and stopping gambling temporarily does not by itself demonstrate long-term recovery. An evidence-based assessment should specify the intended clinical outcome before medication starts and revisit it during treatment. Dowling et al. (2022); NICE (2025).

Clinical recognition versus research outcomes

Many older trials recruited participants under DSM-IV pathological gambling criteria, while clinical practice now uses updated diagnostic systems, including DSM-5-TR and ICD-11. The underlying presentations overlap substantially, but study eligibility, symptom thresholds, and outcome instruments vary. A trial reporting improvement on the Pathological Gambling Adaptation of the Yale-Brown Obsessive Compulsive Scale (PG-YBOCS), for example, describes change on a research measure; it does not establish that each participant no longer met contemporary diagnostic criteria. Grant, Kim, and Hartman (2008); WHO (2024).

Why opioid-receptor antagonists are studied

Gambling engages learning, anticipation, decision-making, affective regulation, and motivational systems. Intermittent rewards, near misses, loss chasing, cues associated with betting, and opportunities to gamble can sustain repeated behavior. Endogenous opioid signaling interacts with reward-related neural processes, providing a plausible rationale for examining opioid-receptor antagonists that alter the response to rewarding experiences. Naltrexone and nalmefene were therefore investigated as potential ways to reduce gambling urges and symptom severity. Grant et al. (2006); Grant, Kim, and Hartman (2008).

This mechanism is a pharmacological hypothesis supported by some clinical observations and randomized trials. Researchers have not demonstrated that gambling disorder results from a single opioid-system abnormality, or that an opioid antagonist corrects a universal neurological defect. People gamble for many interacting reasons, including arousal, escape from distress, learned expectations, perceived financial opportunity, and social or digital exposure. A biological rationale therefore informs drug development while actual treatment benefits must be demonstrated by controlled outcomes and patient-important changes. Dowling et al. (2022); Ioannidis et al. (2025).

Craving and reward are only part of the clinical picture

The hope that reducing gambling urges will help some patients is reasonable, particularly where powerful urges repeatedly defeat intentions to stop. Yet gambling-related behavior also depends on exposure to fast digital betting, access to credit, debts, mood symptoms, distorted beliefs about winning, and the immediate availability of opportunities to bet. Medication alone does not block accounts, reverse losses, negotiate financial arrangements, repair relationships, or teach coping skills. This is one reason gambling-specific psychological interventions and environmental safeguards remain central in clinical guidelines. NICE (2025).

Naltrexone: what clinical studies show

Naltrexone is an opioid-receptor antagonist already used for certain alcohol- and opioid-related conditions. Its investigation for gambling disorder is a separate, off-label indication. Investigators have tested oral naltrexone against placebo in randomized, double-blind studies. In a trial reported by Grant, Kim, and Hartman, 77 adults with pathological gambling and gambling urges were assigned to placebo or different naltrexone regimens over 18 weeks. The investigators assessed urges, gambling behaviors, symptom severity, and functioning. This trial contributes to the evidence that some patients experience clinically relevant improvement, although it was relatively small and cannot identify a universally effective regimen. Grant, Kim, and Hartman (2008).

An earlier controlled trial also studied naltrexone, illustrating that opioid antagonism has been considered in gambling treatment for more than two decades. Across studies, variation in treatment duration, participant selection, doses, coexisting conditions, and outcome scales makes individual trial results difficult to generalize. High trial doses should not be copied into self-treatment, and a positive trial result is not proof of safety or effectiveness for a particular patient. Kim et al. (2001); Dowling et al. (2022).

What the Cochrane review found

A 2022 Cochrane review included 17 randomized studies with 1,193 randomized participants across different pharmacological classes. Four studies involving 562 people examined opioid antagonists; the pooled analysis of gambling severity relied on 259 participants and found a short-term advantage over placebo, with a standardized mean difference of −0.46 (95% confidence interval −0.74 to −0.19). The pooled responder outcome, however, remained uncertain. The review judged much of the evidence low or very low certainty because of modest sample sizes, imprecision, bias concerns, differences among studies, and limited follow-up. It also noted that trials often excluded people with psychiatric comorbidities commonly seen in practice. Dowling et al. (2022).

The conclusion is narrower than a blanket claim that medication works for gambling addiction. It suggests a possible reduction in measured gambling severity in the short term for opioid-antagonist treatment as a class, while leaving important questions about abstinence, sustained recovery, life functioning, and patient selection unresolved. Different medications within a class also have distinct profiles. The review did not establish a first-line drug for everyone with gambling disorder. Cochrane (2022).

What the 2025 network meta-analysis adds

A later systematic review identified 22 double-blind randomized medication trials and used 16 trials involving 977 participants in a network meta-analysis. Network meta-analysis combines direct and indirect comparisons across interventions, subject to assumptions about the comparability of studies and patients. Nalmefene showed an estimated advantage over placebo for gambling severity (standardized mean difference −0.86, 95% CI −1.32 to −0.41). Naltrexone's corresponding estimate was −0.42 (95% CI −0.85 to 0.01); the interval crossed zero, making its severity result less conclusive on that analysis. Ioannidis et al. (2025).

The network analysis also found an advantage in quality-of-life scores for naltrexone versus placebo (standardized mean difference −0.50, 95% CI −0.85 to −0.14), but its findings require evaluation alongside tolerability. Treatment discontinuation due to adverse effects was more frequent than with placebo for both naltrexone (odds ratio 7.82, 95% CI 1.26 to 48.70) and nalmefene (odds ratio 7.55, 95% CI 2.24 to 25.41). The wide confidence intervals signal imprecision: these are comparative trial estimates, not predictions of an individual's probability of side effects. The authors concluded that these antagonists had the strongest medication evidence among the options compared and called for larger, better individualized research. Ioannidis et al. (2025).

How the two major syntheses fit together

The Cochrane findings and network estimates address related but different datasets and statistical questions. Cochrane pooled placebo-controlled evidence by drug category and emphasized low certainty; the newer network analysis compared specific medications using a broader set of trial comparisons and identified both possible benefits and a tolerability penalty. There is no need to force their conclusions into a single drug-effect number. Taken together, they support a carefully selected specialist option, with considerable uncertainty about treatment beyond a few months and about people with substantial psychiatric comorbidity. Cochrane (2022); Ioannidis et al. (2025).

A 2026 systematic review of medication trials

A 2026 systematic review published in Tijdschrift voor Psychiatrie identified 24 double-blind randomized trials involving 1,547 participants. Among seven studies of opioid antagonists, four reported statistically better results than placebo; results for other medication classes were less consistent. Methodological differences prevented the authors from performing a pooled meta-analysis. They concluded that off-label opioid antagonists may be considered following inadequate response to psychotherapy, while evidence does not establish other investigated medications as treatments for gambling disorder. The broader study count strengthens the evidence map without resolving questions about long-term outcomes, safety, or personalized selection. Neven, van Zundert, and Suranto (2026).

What clinical guidelines actually recommend

The National Institute for Health and Care Excellence published guideline NG248 in January 2025. It recommends offering gambling-specific CBT and considering motivational interviewing to help engagement. For pharmacotherapy, it advises considering naltrexone when an appropriate course of psychological therapy has not achieved desired outcomes or when repeated relapse occurs despite psychological therapy. Initiation should be by, or supervised by, an appropriately qualified and experienced specialist. Continuing psychological therapy alongside medication should be considered. These recommendations describe a treatment pathway and a decision-making process rather than a drug prescription for everyone who gambles excessively. NICE (2025).

NICE explicitly identified naltrexone for gambling-related harm as an off-label use in January 2025. Its rationale states that pharmacological evidence was insufficient to recommend naltrexone as a first-line therapy; the committee combined limited study evidence with specialist judgment in making a conditional recommendation. The committee did not recommend nalmefene in national guidance because gambling-trial doses differed from established licensed dosing for another indication and the committee lacked relevant prescribing experience. This is an example of a guideline weighing feasibility and safety along with estimated efficacy. NICE rationale (2025).

What off-label prescribing means

An off-label prescription uses an authorized medication for a condition or in a manner outside its specific marketing approval. That status does not by itself establish effectiveness or harm; it places greater importance on clinical justification, informed discussion, monitoring, and local professional and legal rules. Naltrexone's established use in alcohol or opioid treatment should never be interpreted as regulatory approval for treating gambling disorder. A treatment plan needs to distinguish the licensed indication, the research indication, and the medical issues of the particular patient. NICE (2025); DailyMed (2026).

Does the NICE recommendation apply everywhere?

NICE NG248 is guidance for a particular healthcare system, published in England. It is valuable internationally as a transparent synthesis of the evidence and a clinical decision model, while drug authorization, specialist access, local prescribing rules, and the treatment resources available differ by country. In the United States, a psychiatrist or another licensed prescriber must weigh the available studies and product labeling within American standards of care. The evidence does not justify readers ordering naltrexone without a prescribing assessment. NICE (2025); DailyMed (2026).

Naltrexone safety: the central prescribing questions

Naltrexone safety depends on opioid exposure, liver health, other medicines, clinical status, and monitoring. It blocks opioid receptors and can precipitate withdrawal in a person who is physiologically dependent on opioids; it can also interfere with opioid-containing pain treatment. The treatment history must therefore cover prescribed opioid pain relievers, opioid-use disorder medications, illicit opioids, certain cough medicines, and other products that may contain opioids. Disclosure matters because a patient may use a prescription opioid intermittently and not think of it as part of addiction treatment. DailyMed (2026).

Opioid exposure and precipitated withdrawal

Initiating naltrexone while opioid agonists remain active in a dependent patient can trigger rapid, severe withdrawal requiring medical attention. An appropriate opioid-free interval is determined by a clinician based on the specific substances, timing, dependence, and clinical evaluation. Product labeling warns that the interval following methadone or buprenorphine may be longer than after some short-acting opioids, and that testing does not eliminate all uncertainty. Patients should never try to establish eligibility by suddenly stopping opioid maintenance medication or by conducting an unsupervised opioid challenge. DailyMed (2026).

Emergency pain care and overdose after discontinuation

While taking naltrexone, opioid analgesics may have reduced effects, complicating emergency or surgical pain care. All treating clinicians should know about the medication so pain management can be planned safely. Attempting to overcome receptor blockade by taking large amounts of opioids can cause fatal overdose. After naltrexone is discontinued, decreased opioid tolerance can leave a person vulnerable to overdose at doses previously tolerated. These risks are especially relevant when gambling disorder coexists with opioid-use disorder, ongoing opioid analgesic treatment, or relapse risk. DailyMed (2026).

Liver, kidney, and other medical assessment

NICE recommends that clinicians check kidney and liver function before naltrexone and arrange follow-up to assess efficacy and adverse effects, including liver-function monitoring. Drug labeling warns about hepatic injury and advises clinical evaluation if symptoms suggest acute hepatitis. A prescriber should consider existing liver disease, alcohol use, other potentially hepatotoxic medications, and the medical significance of laboratory results. Monitoring continues during treatment and should respond to new symptoms. NICE (2025); DailyMed (2026).

Adverse effects, tolerability, and adherence

Nausea, dizziness, headache, sleep disturbances, and other adverse effects have appeared in opioid-antagonist research and drug information. The clinically important question is whether a possible reduction in gambling severity outweighs side effects, the burden of monitoring, and the alternatives for a particular person. In the 2025 network analysis, more participants discontinued opioid antagonists because of medication side effects than placebo. Such discontinuation influences real-world effectiveness: a drug that helps on a scale in a short trial may offer little sustainable benefit when its adverse effects make ongoing treatment impractical. Ioannidis et al. (2025); Grant et al. (2006).

Pregnancy, age, and coexisting illness

Prescribing decisions should include pregnancy and breastfeeding considerations, age, medication interactions, organ function, and individual medical history. Evidence from adult gambling-treatment trials cannot be assumed to apply to adolescents, pregnant patients, or people with unstable medical conditions. For adolescents with gambling-related harm, a developmentally appropriate psychological and family-based approach requires specialist evaluation; gambling medication studies do not establish a routine adolescent pharmacotherapy pathway. These populations highlight the difference between general drug prescribing experience and efficacy evidence for the specific gambling indication. Dowling et al. (2022); NICE (2025).

Other medications studied for gambling disorder

Nalmefene

Nalmefene is another opioid antagonist investigated for gambling symptoms. A multicenter randomized trial of 207 participants reported reductions in gambling severity in some nalmefene groups compared with placebo over 16 weeks; adverse effects included nausea, dizziness, and insomnia. The 2025 network analysis estimated a substantial reduction in gambling symptom severity but also a higher adverse-effect dropout rate. Although these are meaningful research signals, they do not establish a universally preferred medication or a routine nalmefene prescribing strategy. NICE considered its gambling-trial dosage and clinical experience insufficient to support a recommendation. Grant et al. (2006); Ioannidis et al. (2025); NICE rationale (2025).

Antidepressants

Antidepressants have been tested because gambling disorder frequently overlaps with depression, anxiety, and other psychiatric symptoms, and some older models emphasized compulsivity. The Cochrane review pooled six antidepressant studies with 268 participants and found no clear advantage over placebo on gambling severity and several other pooled outcomes. This does not mean antidepressants lack value for a patient who independently meets criteria for depression or an anxiety disorder. It means treatment of a coexisting disorder and demonstrated treatment of gambling symptoms are separate clinical questions. Dowling et al. (2022).

Mood stabilizers and anticonvulsants

Mood stabilizers and anticonvulsants have also been explored. Existing trials are too limited and heterogeneous to establish them as treatments for gambling disorder itself. Some participants may need mood-stabilizing medication for a separate diagnosis such as bipolar disorder, where the justification comes from that disorder's treatment evidence. Clinicians must also distinguish gambling behavior occurring during a manic episode from the persistent pattern associated with gambling disorder. Medication selection should follow accurate differential diagnosis and associated risk, rather than treating any impulsive gambling as proof of one particular condition. Dowling et al. (2022); NICE (2025).

Antipsychotics and paradoxical medication-related gambling

Trials of atypical antipsychotics produced inconsistent evidence. A review of randomized studies offered tentative signals from some small olanzapine studies, whereas the later network meta-analysis found olanzapine no more effective than placebo for gambling severity. Routine antipsychotic treatment of gambling disorder is therefore unsupported by a reliable overall benefit-risk case. Antipsychotics can also have side effects unrelated to gambling and should be used only for an appropriate individualized indication. Dowling et al. (2022); Ioannidis et al. (2025).

A separate and clinically important issue is the potential for certain medicines to contribute to new gambling urges. The U.S. Food and Drug Administration identifies impulse-control problems, including gambling, among warnings associated with aripiprazole. Medicines affecting dopamine function, including treatments used for Parkinson's disease, also warrant review when new gambling behavior emerges. NICE recommends assessing current pharmacotherapy as a possible contributor. Decisions to change these drugs require the prescriber's involvement because sudden discontinuation or unmanaged substitution can create additional risks. FDA (2016, updated 2023); NICE (2025).

Medication alongside psychological and practical treatment

CBT and motivational interventions

Gambling-focused CBT typically works with gambling triggers, cognitive distortions, behavioral routines, emotional coping, high-risk situations, and relapse prevention. Motivational interviewing can help people who feel ambivalent about treatment. These modalities address aspects of gambling that an opioid antagonist alone cannot directly change. A 2023 systematic review of 29 CBT studies with 3,991 participants reported significant immediate post-treatment improvements in gambling severity and behavior compared with minimal or no treatment, while also identifying heterogeneity, publication bias, and uncertain longer-term advantage. The evidence supports offering structured treatment with realistic discussions of durability rather than promising a permanent cure. Pfund et al. (2023); NICE (2025).

Financial, platform, and social supports

A comprehensive plan may include self-exclusion from gambling venues and services, blocking or access restrictions, limits on immediate access to funds, help with debt and financial safeguarding, and support for affected partners or family members. Such actions can reduce opportunities to gamble while a person develops new coping strategies. They require an individualized approach that considers financial control, privacy, safety, and consent. Drug trials rarely measure these dimensions sufficiently, although they often determine whether an improvement on a symptom scale becomes meaningful recovery in daily life. NICE (2025).

A medication review is one part of a recovery review

Clinicians should ask what improvement means to the patient: fewer episodes, lower urge intensity, abstinence, financial stability, better sleep, improved mood, reduced secrecy, restored daily function, or fewer crises. Some goals require additional services and longer-term follow-up. If gambling continues, evaluation should reconsider the formulation, treatment engagement, environmental exposure, coexisting disorders, and medication tolerance rather than automatically escalating medication. NICE recommends further support and access to renewed treatment after a lapse or relapse. NICE (2025).

Who might be evaluated for medication?

A specialist assessment may be appropriate when clinically significant gambling disorder persists despite a completed, suitable psychological intervention or when gambling repeatedly returns after treatment, particularly when urges are intense and the person is willing to discuss medication. A careful assessment explores treatment history, severity, gambling triggers, psychiatric comorbidity, possible medication-induced gambling, alcohol or other substance use, medical conditions, current medications, and the patient's preferences. This is a clinical decision, not an eligibility checklist to be used alone. NICE (2025).

Depression, anxiety, ADHD, bipolar disorder, and substance use

Psychiatric comorbidity is common enough in gambling services that it matters for study generalizability and individualized care. Depression or anxiety may both contribute to gambling-related distress and follow from financial, interpersonal, or other harms. ADHD-associated executive-function difficulties may influence impulsive decisions without independently determining a gambling diagnosis or a drug choice. Bipolar disorder requires careful attention to episodes of mania or hypomania and any treatment-associated disinhibition. Alcohol and other substance use can increase medical complexity, impair judgment, or alter the safety of prescribing an opioid antagonist. Clinical formulation determines which symptoms belong to which condition and which services should work together. NICE (2025); Dowling et al. (2022).

Many gambling pharmacotherapy trials excluded participants with significant psychiatric comorbidities, limiting their external validity. A trial in selected adults with stable circumstances cannot establish whether the same average result will occur in a person managing depression, opioid maintenance treatment, bipolar disorder, or severe financial crisis. The absence of adequate trial evidence for a subgroup calls for better research and careful clinical judgment. Dowling et al. (2022); NICE research recommendations (2025).

Gambling disorder, medication, and suicide risk

Gambling-related harms can coincide with suicidal thoughts, self-harm, and acute crises, particularly when severe debt, relationship breakdown, shame, or coexisting psychiatric symptoms converge. The presence of imminent suicide risk calls for urgent safety assessment and appropriate crisis care; it must not be reduced to a routine medication decision. NICE explicitly emphasizes assessment of suicidality, safety planning where needed, and vigilance around relapse. A medication trial showing fewer gambling symptoms does not establish that medication prevents suicide. NICE (2025); WHO (2024).

When someone has a current intention to harm themselves, a plan, access to lethal means, or cannot maintain safety, immediate contact with local emergency services or an emergency department is warranted. For other suicidal thoughts, prompt assessment by a qualified health professional is important. A care plan may involve collaborative safety planning, appropriate involvement of trusted people, access restrictions that reduce acute financial or gambling triggers, and direct treatment of coexisting disorders. Discussion of naltrexone can resume within a medically supervised treatment plan that addresses immediate safety first. NICE (2025).

How clinicians evaluate response to medication

At baseline, a clinician may document diagnostic criteria, recent gambling episodes, expenditure and time spent gambling, urge intensity, functional impairment, psychological distress, psychiatric and substance-use diagnoses, liver and kidney status, medications, and safety risk. Subsequent follow-up should ask about both perceived benefit and adverse effects, adherence, new or continuing gambling harms, and any unexpected changes in mood. The follow-up schedule and testing are individualized. NICE recommends regular monitoring and continued consideration of psychological treatment. NICE (2025).

A scale score is only one signal. Meaningful outcomes include sustained reduction in harmful behavior, greater control in high-risk settings, improved function, protection from debt escalation, relationships, and patient-valued progress. Evidence from a medication trial is stronger when outcomes are prespecified, compare randomized groups, include withdrawals, and report harms. Observing reduced gambling after starting medication in a single case cannot separate the drug's effects from motivation, social supports, regression to the mean, or simultaneous therapy. The substantial improvements sometimes observed in placebo groups underscore this interpretive problem. Dowling et al. (2022); Ioannidis et al. (2025).

What remains uncertain in the medication evidence?

Trial size, duration, and selective enrollment

The strongest limitation is the modest evidence base. A network of fewer than a thousand trial participants across many treatment comparisons cannot offer precision for every medication, subgroup, and outcome. Many studies were brief, and long-term outcomes remain insufficiently established. Attrition, small samples, variable outcome measures, lack of replication, and exclusion of clinically complex patients restrict confidence in durability and generalizability. Large, adequately powered trials with standardized measures and extended follow-up are necessary to determine which patients experience benefits that outweigh adverse effects. Cochrane (2022); Ioannidis et al. (2025).

Comparators, placebo response, and multiple outcomes

Some trials report improvements within the active treatment group without a clear advantage against placebo. These are different findings. Drug assignment in a blinded randomized study helps control for expectancy and background improvement, while meta-analytic comparisons bring additional assumptions and uncertainty. If a study measures urge, symptom severity, expenditure, abstinence, functioning, and mood, a positive result on one outcome should not be generalized to all the others. A trustworthy synthesis states the outcome, comparison, duration, and interval estimate. Dowling et al. (2022); Ioannidis et al. (2025).

Combining medication with therapy

A person may receive naltrexone while undertaking CBT or other psychosocial interventions. Such care can be clinically sensible, and NICE suggests considering continued therapy when naltrexone is started. Yet evidence about the additive benefit of combining medication and psychological treatment is limited. We cannot assume that two individually promising components necessarily yield a predictable combined effect. NICE specifically identified combination approaches and comorbid populations as priorities for further investigation. NICE research recommendations (2025).

Research classification and digital gambling environments

Many foundational trials were conducted before the present scale of mobile sports betting, instant deposits, round-the-clock advertising, and other rapidly available gambling products. The central clinical disorder remains recognizable, but the frequency and structure of gambling opportunities can alter triggers and adherence challenges. A finding from a land-based or mixed gambling sample may require evaluation in contemporary online contexts. Researchers should measure exposure, gambling forms, behavior, harms, and socioeconomic context while maintaining the distinction between clinically diagnosed disorder and screening-defined risk. WHO (2024); NICE (2025).

Questions patients and clinicians commonly ask

Is naltrexone approved specifically for gambling addiction?

Naltrexone is prescribed for approved alcohol- and opioid-related indications in the United States; gambling disorder remains an off-label indication. NICE in England recommends considering it under specialist supervision after insufficient response to an appropriate psychological therapy course or repeated relapse, with appropriate safety checks and follow-up. A recommendation to consider treatment is not proof of regulatory approval for gambling disorder. DailyMed (2026); NICE (2025).

Does naltrexone eliminate the desire to gamble?

Clinical trials suggest that opioid antagonists can reduce measured gambling severity in some participants; responses vary, and the evidence does not support a universal elimination of craving or a guaranteed return of control. Financial and social harms and access to gambling also require direct attention. Clinicians measure the actual effect in each patient and reconsider treatment if the hoped-for benefits do not emerge. Cochrane (2022).

Is nalmefene better than naltrexone?

A 2025 network meta-analysis estimated a larger effect for nalmefene on gambling severity, but differences in comparisons, population selection, uncertainty, and tolerability prevent a simple ranking for an individual patient. Both drugs had more discontinuations due to side effects than placebo. NICE chose to recommend considering naltrexone, rather than nalmefene, in its specified clinical pathway. Ioannidis et al. (2025); NICE rationale (2025).

Can someone take naltrexone while using opioid pain medicine?

Opioid exposure is a major contraindication and safety issue because naltrexone can precipitate withdrawal in opioid-dependent individuals and block opioid analgesia. The appropriate assessment considers all prescribed and nonprescribed opioids and future pain needs. Patients should discuss the situation with the treating clinician and must not attempt an unsupervised change to either medicine. DailyMed (2026).

How long must medication be continued?

NICE describes a monitored prescribing course, but the gambling-treatment trials do not establish a universal duration that optimizes long-term outcomes. Duration should follow response, tolerability, monitoring results, risk, patient goals, and specialist judgment. Long-term recovery planning and relapse-prevention support remain important whether medication is used, discontinued, or never prescribed. NICE (2025); Cochrane (2022).

What should happen if gambling urges return?

The care team should reassess exposure, triggers, comorbid symptoms, medication safety, psychological treatment needs, and immediate harms. A lapse deserves rapid access to support and any necessary safety assessment, not an automatic medication escalation. NICE recommends supportive, nonstigmatizing relapse care with additional treatment when appropriate. NICE (2025).

Clinical conclusion

Naltrexone is a reasonable specialist consideration for selected adults with gambling disorder after appropriate psychological treatment has delivered insufficient benefit or when repeated relapse occurs. The strongest pharmacological evidence concerns opioid-receptor antagonists and predominantly short-term changes in gambling symptom severity; durable effects, specific responder characteristics, and benefits for many medically complex populations remain uncertain. The clinical choice must combine the limited efficacy evidence with adverse-effect and opioid-related safety risks, patient preferences, continued psychological care, and active measures addressing gambling opportunities and consequences. NICE (2025); Dowling et al. (2022); Ioannidis et al. (2025).

Gambling Disorder Treatment: Psychological Care and Recovery — The broader clinical pathway, with CBT, motivational approaches, coordinated services, and recovery planning.

Gambling Disorder: Symptoms, Diagnosis, and Treatment — Diagnostic criteria and assessment of gambling disorder before a treatment plan is chosen.

How to Stop Gambling: Evidence-Based First Steps and Ongoing Support — Practical changes and supports that complement specialist care.

Cluster Gambling, Gaming and Behavioral Addictions — Scientific overview connecting gambling and gaming disorders, assessment, mechanisms, products, and recovery.