Naltrexone + Bupropion for Smoking Cessation in Schizophrenia

Overseen By Jin H Yoon, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: Naltrexone, Bupropion

Disqualifiers: Suicidal ideation, Alcohol use disorder, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether using injectable naltrexone and oral bupropion (an antidepressant) together is safe and practical for people with schizophrenia who smoke cigarettes. Researchers seek to determine if this combination can help reduce smoking and improve symptoms related to schizophrenia. The study seeks participants with a stable form of schizophrenia who smoke at least five cigarettes a day and are not currently using opioids. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are taking medications that should not be used with naltrexone or bupropion.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using naltrexone and bupropion together is generally safe. A large study in Sweden found that bupropion did not significantly increase the risk of serious side effects, suggesting the combination is safe for people trying to quit smoking, including those with schizophrenia. Bupropion is known to help with nicotine withdrawal symptoms, such as irritability and mood swings.

However, one study did not find a strong effect on quitting smoking in people with schizophrenia, but it also reported no serious safety issues. While these findings are encouraging, the trial remains in an early phase, focusing primarily on safety rather than the treatment's effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using Naltrexone and Bupropion for smoking cessation in individuals with schizophrenia because this combination targets the brain's reward system in a unique way. Most current treatments for smoking cessation focus on nicotine replacement or modulating dopamine alone, but Naltrexone, an opioid receptor antagonist, and Bupropion, a norepinephrine-dopamine reuptake inhibitor, work together to reduce cravings and withdrawal symptoms by affecting multiple neurotransmitter pathways. This dual-action approach has the potential to be more effective than current options, offering new hope for individuals who struggle with both schizophrenia and nicotine addiction.

What evidence suggests that this treatment might be an effective treatment for smoking cessation in schizophrenia?

Research has shown that using naltrexone and bupropion together might help people quit smoking and manage nicotine addiction. This trial will evaluate the combination of naltrexone and bupropion for smoking cessation in individuals with schizophrenia. Some studies suggest this combination can address both the physical and mental aspects of smoking addiction. This is particularly important for people with schizophrenia who smoke, as it might not only help them quit smoking but also improve some symptoms of schizophrenia. Although one study did not find a significant effect on smoking cessation for people with schizophrenia, hope remains because this approach addresses different aspects of addiction. Early results are promising, but more research is needed for confirmation. ^{1 2 3 4 5}

Who Is on the Research Team?

Jin H Yoon, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for adults with schizophrenia who smoke cigarettes and are interested in quitting. Participants should be stable on their antipsychotic medication, not currently pregnant or breastfeeding, and without a history of seizures or opioid use.

Inclusion Criteria

My schizophrenia is currently under control.

Obtain an Evaluation to Sign Consent (ESC) score above 10

I am not pregnant, breastfeeding, and agree to use birth control and undergo pregnancy tests during the study.

Exclusion Criteria

Currently enrolled in treatment for tobacco use

Have suicidal or homicidal ideation requiring immediate attention

I am not on medications that interfere with naltrexone or bupropion.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive injectable naltrexone and oral bupropion for 3 weeks

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bupropion
• Naltrexone

Trial Overview The study tests the combination of injectable Naltrexone (380 mg) and oral Bupropion (450 mg daily) to see if it helps people with schizophrenia quit smoking. It will also look at how this combo affects their schizophrenia symptoms.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 2 Interventions

Bupropion is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in European Union as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in Canada as Zyban for:

• Smoking cessation

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

A systematic review of 12 trials found that first-line pharmacotherapies for smoking cessation, such as varenicline, bupropion, and nicotine replacement therapies, are effective and safe for smokers with schizophrenia, addressing their unique challenges in quitting smoking.

The review highlights the need for further research on the long-term effectiveness and safety of these treatments in community settings, suggesting that emerging methods like electronic nicotine delivery systems and neuromodulation techniques could also be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for smoking cessation in schizophrenia: a systematic review. Kozak, K., George, TP.[2021]

Bupropion SR has been shown to be more effective than a placebo for smoking cessation, improving both initial and long-term abstinence rates based on data from over 8000 patients in clinical trials.

While generally well tolerated, the main risks associated with bupropion SR include a low incidence of seizures (approximately 0.1%) and hypersensitivity reactions (about 0.12%), but the benefits of treatment, such as saving lives and reducing smoking-related health issues, outweigh these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bupropion SR for smoking cessation: data from clinical trials and five years of postmarketing experience. Ferry, L., Johnston, JA.[2013]

A large population-based study in Sweden found that neither bupropion nor varenicline significantly increased the risk of serious adverse outcomes like myocardial infarction, stroke, or suicide when used for smoking cessation, suggesting they are relatively safe options.

The study analyzed data from various time periods and included a substantial number of cases, reinforcing the conclusion that these medications do not consistently pose higher risks for the adverse outcomes examined, provided prescription guidelines are followed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment With Bupropion and Varenicline for Smoking Cessation and the Risk of Acute Cardiovascular Events and Injuries: a Swedish Case-Crossover Study. Monárrez-Espino, J., Galanti, MR., Hansson, J., et al.[2022]

In a study of 390 smokers with schizophrenia, varenicline was found to significantly increase abstinence rates compared to placebo, with a number needed to treat (NNT) similar to that of a control group without psychiatric illness.

No treatment, including varenicline, bupropion, or nicotine replacement therapy, was associated with a higher incidence of neuropsychiatric adverse events compared to placebo, indicating that these treatments are safe for smokers with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Pharmacotherapeutic Smoking Cessation Aids in Schizophrenia Spectrum Disorders: Subgroup Analysis of EAGLES. Evins, AE., West, R., Benowitz, NL., et al.[2023]

Varenicline users did not show worse mental health compared to current smokers or those who quit without medication, suggesting it may be a safe option for smoking cessation in terms of psychiatric effects.

In contrast, bupropion was linked to significantly lower mental health status across all groups, indicating potential risks for users, even after accounting for pre-existing psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mental health status of varenicline and bupropion users during a quit attempt compared to current smokers, other quitters, and non-smokers. Shewale, AR., Borse, MS., Brown, JD., et al.[2022]

In a study involving 78 veterans participating in a smoking cessation program, only 22% were deemed appropriate candidates for bupropion SR (Zyban) treatment, indicating limited applicability in this population.

The findings suggest that while bupropion SR is effective for smoking cessation, its use may be restricted by conservative prescribing guidelines, raising concerns about its broader applicability without complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suitability of bupropion SR for nicotine-dependent smokers: problems in a practice setting. Kohlenberg, BS., Antonuccio, DO., Hayes, SC., et al.[2017]

In a 10-week study involving 58 smokers with schizophrenia, the combination of sustained-release bupropion and a transdermal nicotine patch significantly increased the likelihood of achieving continuous smoking abstinence compared to a placebo plus nicotine patch, with 27.6% of participants in the treatment group abstaining versus only 3.4% in the placebo group.

The combination therapy was well-tolerated and did not significantly affect the positive or negative symptoms of schizophrenia, indicating it may be a safe option for smoking cessation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia. George, TP., Vessicchio, JC., Sacco, KA., et al.[2022]

Patients with schizophrenia can effectively reduce smoking through treatment interventions, with significant reductions maintained for up to 2 years.

Bupropion is a safe and well-tolerated option for smoking cessation in schizophrenia patients, enhancing abstinence rates without worsening their clinical symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tobacco and schizophrenia: therapeutic aspects]. Dervaux, A., Laqueille, X.[2020]

In a study of 53 adults with schizophrenia, those taking bupropion were significantly more likely to quit smoking compared to those on a placebo, with 36% abstinent one week after quitting and 16% at the end of the 12-week intervention.

Bupropion did not worsen schizophrenia symptoms and even showed a trend toward improvement in depressive symptoms, but the effectiveness for smoking cessation did not last after stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia. Evins, AE., Cather, C., Deckersbach, T., et al.[2022]

Bupropion, an atypical antidepressant used for smoking cessation, can induce psychotic episodes in some patients, typically occurring after about 10 days of treatment at a dose of 300 mg/day, with 85% of cases reporting hallucinations.

Most patients experiencing bupropion-induced psychosis had no prior psychiatric history, suggesting that the drug may cause dopaminergic hyper-reactivity, and discontinuation usually leads to remission within 10 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acute psychotic disorders related to bupropion: review of the literature]. Javelot, T., Javelot, H., Baratta, A., et al.[2013]

In a 3-month study involving 19 patients with schizophrenia, adding sustained-release bupropion to cognitive behavioral therapy (CBT) significantly reduced smoking behavior, with 66% of participants in the bupropion group showing a reduction compared to only 11% in the placebo group.

Bupropion treatment not only helped reduce smoking but also improved negative psychiatric symptoms and provided greater stability in psychotic and depressive symptoms during the quit attempt, suggesting it is a beneficial adjunct therapy for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia. Evins, AE., Mays, VK., Rigotti, NA., et al.[2022]

Adding bupropion SR to high-dose nicotine replacement therapy and cognitive behavioral therapy significantly improved smoking reduction rates in adults with schizophrenia, with 60% achieving 50% to 100% reduction compared to 31% in the placebo group after 12 weeks.

Despite initial success in smoking reduction and lower carbon monoxide levels, relapse rates were high after treatment tapering, highlighting the need for longer-term strategies to maintain abstinence beyond the initial treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 12-week double-blind, placebo-controlled study of bupropion sr added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia. Evins, AE., Cather, C., Culhane, MA., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5850123/

Naltrexone and Bupropion Combination Treatment for ... Conclusion: Naltrexone and bupropion combination treatment didn't show weight loss or smoking cessation effect in patients with schizophrenia ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02736474

Study Details | NCT02736474 | Naltrexone and Bupropion ... The purpose of this research is to observe the efficacy of Naltrexone and Bupropion combination on weight loss and smoking cessation from baseline to week ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5017904/

Bupropion and Naltrexone for Smoking Cessation This study is clinically significant in that it demonstrates the efficacy of combining BUP and NTX on the primary outcomes of smoking cessation and nicotine ...

4. withpower.com withpower.com/trial/phase-1-schizophrenia-3-2024-a8e1a

Naltrexone + Bupropion for Smoking Cessation in ... This combination may offer a novel approach by targeting both the chemical and behavioral aspects of smoking addiction in people with schizophrenia.

5. tandfonline.com tandfonline.com/doi/abs/10.1080/14737175.2022.2124369

Is there a therapeutic potential in combining bupropion and ... We hypothesize that BUPNAT can have a therapeutic effect in schizophrenia, particularly on negative symptoms.