Low-Dose Buprenorphine for Schizophrenia

Overseen By Gerard De Vera

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Los Angeles

Must not be taking: Opioids, Sedatives, Benzodiazepines

Disqualifiers: Neurological, Cardiovascular, Respiratory, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 2 days

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have changed your medications in the past 6 months and cannot use sedatives or benzodiazepines within 24 hours of testing.

What data supports the effectiveness of the drug Buprenorphine for treating schizophrenia?

There is no direct evidence from the provided research that supports the effectiveness of Buprenorphine for treating schizophrenia. However, Buprenorphine is used for opioid use disorder, and managing both opioid use disorder and schizophrenia together can improve patient outcomes. ^{1 2 3 4 5}

Is low-dose buprenorphine generally safe for humans?

Buprenorphine has been used safely for treating opioid use disorder, with studies showing it is well tolerated in short-term detoxification settings. However, abrupt discontinuation can lead to rare cases of psychosis, and it has potential for abuse, especially when used intravenously. ^{1 2 6 7 8}

How does the drug Buprenorphine differ from other treatments for schizophrenia?

Buprenorphine is unique for schizophrenia treatment as it is primarily used for opioid addiction and pain management, and its use in schizophrenia is novel, especially at low doses. This approach may target brain reward circuitry dysfunction, which is a potential underlying issue in patients with schizophrenia and co-occurring substance use disorders. ^{3 5 9 10 11}

What is the purpose of this trial?

Low social motivation is a significant symptom of schizophrenia and is a major cause of disability and suffering for many patients struggling with the illness. Social motivation refers to the drive to participate in or abstain from social activities. Many patients with schizophrenia evidence both decreased drive to seek positive social input (approach motivation) and heightened drive to avoid negative social input (avoidance motivation) compared to individuals without the illness. Despite the enormous burden of these deficits on patients, there are no medications that effectively treat impaired social motivation. Buprenorphine is an unusual drug that is used to treat opioid use disorder at higher doses and more recently, to treat depression and suicidality at lower doses. It is a unique opioid medication that has a compound action that gives it the potential to improve social motivation both by boosting approach motivation and by reducing avoidance motivation. The effects of low doses of buprenorphine have previously. been studied in healthy volunteers, showing that the drug enhances social motivation. These results in nonclinical volunteers suggest that buprenorphine may be a promising treatment for deficits in social motivation seen in some patients with schizophrenia. However, no previous studies have investigated the effects of buprenorphine on social motivation in this population. Here the effects of a low dose of buprenorphine (0.15mg) on social motivation in patients with schizophrenia (N=40) will be assessed. In this double-blind, cross-over, placebo-controlled study, participants will attend a 2-hour preparatory session and two 6-hour laboratory sessions, at which they will receive either placebo or buprenorphine. During expected peak drug effect they will complete validated tasks assessing social motivation. It is expected that buprenorphine will increase approach motivation and decrease avoidance motivation as measured by an attention bias task. The results of this study will lay the foundation for the clinical use of buprenorphine as the first medication to treat social deficits in schizophrenia.

Eligibility Criteria

This trial is for adults aged 18-60 with schizophrenia who have low social motivation, are clinically stable without hospitalizations or medication changes in the past six months, and do not currently use opioids. They should not have significant neurological, cardiovascular, respiratory conditions or a history of serious head injury. Substance abuse within the last six months is also disqualifying.

Inclusion Criteria

able to understand spoken English sufficiently to comprehend testing procedures

score below the mean of participants screened previously screened on the Lubben Social Network Scale

I have been diagnosed with schizophrenia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Session

Participants attend a 2-hour preparatory session

1 day

1 visit (in-person)

Treatment

Participants attend two 6-hour laboratory sessions to receive either placebo or buprenorphine and complete tasks assessing social motivation

2 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Buprenorphine

Trial Overview The study tests if a low dose (0.15mg) of Buprenorphine can improve social motivation in people with schizophrenia compared to a placebo. It's a double-blind study where neither participants nor researchers know who receives the drug or placebo during two lab sessions after an initial preparatory session.

Participant Groups

Group I: Placebo, buprenorphine Experimental Treatment 2 Interventions

One group will receive placebo first, then buprenorphine (0.15mg).

Group II: Buprenorphine, placebo Experimental Treatment 2 Interventions

One group will receive buprenorphine (0.15mg) first, then placebo.

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

Approved in United States as Buprenorphine for:

• Moderate to severe opioid addiction (dependence)

Approved in European Union as Buprenorphine for:

• Opioid dependence

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Findings from Research

A 41-year-old female patient with bipolar disorder experienced new-onset psychosis and a relapse of manic symptoms after abruptly stopping buprenorphine and naloxone (Suboxone), highlighting the potential for withdrawal-induced psychosis in women, which has been underreported in existing literature.

The patient's symptoms improved with hospitalization and treatment using an antipsychotic and a mood stabilizer, suggesting that appropriate medical intervention can effectively manage withdrawal-induced psychosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New-Onset Psychotic Symptoms Following Abrupt Buprenorphine/Naloxone Discontinuation in a Female Patient with Bipolar Disorder: A Case Report. Lin, Y., Zhang, AD., Sun, CF., et al.[2023]

Extended-release depot buprenorphine may be a beneficial treatment option for patients with both opioid use disorder (OUD) and schizophrenia, as it can help manage their conditions concurrently.

The case study highlights the complexities of treating a patient with OUD and psychosis, emphasizing the ethical considerations surrounding involuntary treatment for individuals who may not have the capacity to consent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initiation of Extended-release Depot Buprenorphine in a Patient Subject to a Community Treatment Order for Both Antipsychotic and Opioid Agonist Treatments. Pidutti, J., Cuperfain, AB., Solway, E., et al.[2023]

Patients with schizophrenia often have co-occurring substance use disorders (SUD), which negatively affect their treatment outcomes, highlighting the need for targeted pharmacological strategies.

Preliminary data suggest that atypical antipsychotics, especially clozapine, may be beneficial for treating schizophrenia in patients with SUD, and adjunctive medications like naltrexone could also play a role, but further research is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for schizophrenia and co-occurring substance use disorders. Green, AI.[2019]

In a study of 90 men with both schizophrenia and drug addiction, aripiprazole showed significant improvements in PANSS and BPRS scores compared to haloperidol after 21 days of treatment, indicating its efficacy in managing symptoms of schizophrenia in this population.

Quetiapine also demonstrated significant efficacy compared to haloperidol, particularly in PANSS, VAS, and SACS scores, suggesting that both aripiprazole and quetiapine are effective alternatives for treating patients with dual diagnoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Aripiprazole and quetiapine in the treatment of patients with 'dual diagnosis' of schizophrenia and drug addiction]. Ivanets, NN., Vinnikova, MA., Ezhkova, EV., et al.[2020]

Integrating treatments for substance use disorders (SUDs) with schizophrenia improves patient outcomes, with certain atypical antipsychotics and naltrexone showing particular promise in reducing substance use.

Understanding the neurobiological mechanisms, especially the dysfunction in brain reward circuitry, is crucial for developing effective treatments for SUDs in individuals with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of substance use disorders in schizophrenia: a unifying neurobiological mechanism? Roth, RM., Brunette, MF., Green, AI.[2019]

In a study involving 20 heroin-dependent patients undergoing short-term detoxification, buprenorphine was administered safely with no significant adverse events reported, indicating its tolerability in a psychiatric setting.

The use of buprenorphine led to a significant reduction in withdrawal symptoms, as measured by the Clinical Investigation Narcotic Assessment (CINA) scores, suggesting its potential efficacy for managing heroin withdrawal in hospitalized patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heroin detoxification with buprenorphine on an inpatient psychiatric unit. DiPaula, BA., Schwartz, R., Montoya, ID., et al.[2019]

Clozapine and olanzapine were found to have significant safety signals for infective pneumonia, with clozapine showing a higher reporting odds ratio (aROR: 4.8) compared to haloperidol, indicating a potential increased risk associated with these medications.

The study suggests that the risk of pneumonia may be linked to higher occupancy of muscarinic receptors, highlighting a possible mechanism of action, although further research is needed to confirm these findings and assess clinical implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring a Safety Signal of Antipsychotic-Associated Pneumonia: A Pharmacovigilance-Pharmacodynamic Study. Cepaityte, D., Siafis, S., Egberts, T., et al.[2021]

A survey of intravenous drug users in Helsinki revealed that 73% used buprenorphine as their primary drug, primarily for self-treating addiction or withdrawal symptoms.

The combination of buprenorphine and naloxone (Suboxone) was tried by 68% of respondents, but 80% reported negative experiences, suggesting that while it may help reduce buprenorphine abuse, its acceptance among users is low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Alho, H., Sinclair, D., Vuori, E., et al.[2015]

Brexpiprazole is an effective new treatment for schizophrenia when used alone, providing a novel option for patients managing this condition.

Additionally, brexpiprazole can be used as an adjunctive therapy for major depressive disorder, enhancing the effectiveness of other treatments for individuals with this mental health issue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole (Rexulti): A New Monotherapy for Schizophrenia and Adjunctive Therapy for Major Depressive Disorder. Eaves, S., Rey, JA.[2022]

In a study of 40 patients with schizophrenia and coexisting substance use disorders, treatment with long-acting injectable aripiprazole for 6 months led to significant improvements in psychiatric symptoms, with over a 30% reduction in severity scores.

The treatment also showed promise in managing substance use disorders, with some patients stopping cocaine and alcohol use, indicating that LAI-aripiprazole may be effective for both schizophrenia and substance dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-Monthly Long-Acting Injectable Aripiprazole for the Treatment of Patients with Schizophrenia and Co-occurring Substance Use Disorders: A Multicentre, Observational Study. Szerman, N., Basurte-Villamor, I., Vega, P., et al.[2020]

In a study involving 95 patients with schizophrenia or mania, zuclopenthixol was found to be an effective treatment, showing significant improvements in symptoms like mania and delusions within just two days of administration.

The medication had a favorable safety profile, with minimal side effects such as anticholinergic symptoms and extrapyramidal effects, indicating it is well-tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open multicentre trial of zuclopenthixol in mania and schizophrenia based on the AMDP scales. Bobon, D., Troisfontaines, B., Kempeneers, JL., et al.[2006]

References

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

New-Onset Psychotic Symptoms Following Abrupt Buprenorphine/Naloxone Discontinuation in a Female Patient with Bipolar Disorder: A Case Report. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Initiation of Extended-release Depot Buprenorphine in a Patient Subject to a Community Treatment Order for Both Antipsychotic and Opioid Agonist Treatments. [2023]

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

Pharmacotherapy for schizophrenia and co-occurring substance use disorders. [2019]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Aripiprazole and quetiapine in the treatment of patients with 'dual diagnosis' of schizophrenia and drug addiction]. [2020]

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

Treatment of substance use disorders in schizophrenia: a unifying neurobiological mechanism? [2019]

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

Heroin detoxification with buprenorphine on an inpatient psychiatric unit. [2019]

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

Exploring a Safety Signal of Antipsychotic-Associated Pneumonia: A Pharmacovigilance-Pharmacodynamic Study. [2021]

8. Ireland pubmed.ncbi.nlm.nih.gov

Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. [2015]

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

Brexpiprazole (Rexulti): A New Monotherapy for Schizophrenia and Adjunctive Therapy for Major Depressive Disorder. [2022]

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

Once-Monthly Long-Acting Injectable Aripiprazole for the Treatment of Patients with Schizophrenia and Co-occurring Substance Use Disorders: A Multicentre, Observational Study. [2020]

11. Belgium pubmed.ncbi.nlm.nih.gov

Open multicentre trial of zuclopenthixol in mania and schizophrenia based on the AMDP scales. [2006]