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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the feasibility and safety of injectable naltrexone (NTX;380 mg) in conjunction with oral bupropion (BUP; 450 mg daily)NTX-BUP administration among individuals with schizophrenia spectrum disorders that smoke cigarettes and to evaluate change on smoking-related measures and symptoms of schizophrenia.

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 the drug combination of Naltrexone and Bupropion effective for helping people with schizophrenia quit smoking?

Research shows that Bupropion, when combined with nicotine replacement therapy and cognitive behavioral therapy, can help people with schizophrenia reduce or quit smoking. Studies found that Bupropion led to higher rates of smoking reduction and abstinence without worsening schizophrenia symptoms. ^{1 2 3 4 5}

Is the combination of Naltrexone and Bupropion safe for smoking cessation in people with schizophrenia?

Bupropion is generally well tolerated for smoking cessation, with the most common side effect being insomnia. However, there is a small risk of seizures (0.1%) and serious allergic reactions (0.12%). There are concerns about psychiatric disturbances, but these may be influenced by pre-existing conditions. ^{6 7 8 9 10}

How does the drug Naltrexone + Bupropion for smoking cessation in schizophrenia differ from other treatments?

This drug combination is unique because it combines bupropion, which helps reduce smoking by affecting brain chemicals like dopamine and norepinephrine, with naltrexone, which is typically used to treat alcohol and opioid dependence. This combination may offer a novel approach by targeting both the chemical and behavioral aspects of smoking addiction in people with schizophrenia. ^{1 3 4 11 12}

Research Team

Jin H Yoon, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

References

1. United States 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for smoking cessation in schizophrenia: a systematic review. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Pharmacotherapeutic Smoking Cessation Aids in Schizophrenia Spectrum Disorders: Subgroup Analysis of EAGLES. [2023]

7. Ireland 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. [2022]

8. India pubmed.ncbi.nlm.nih.gov

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

9. England 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. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Suitability of bupropion SR for nicotine-dependent smokers: problems in a practice setting. [2017]

11. France pubmed.ncbi.nlm.nih.gov

[Acute psychotic disorders related to bupropion: review of the literature]. [2013]

12. France pubmed.ncbi.nlm.nih.gov

[Tobacco and schizophrenia: therapeutic aspects]. [2020]