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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a low dose of buprenorphine, a medication often used for pain relief and opioid addiction treatment, can enhance social motivation in people with schizophrenia. Social motivation, the drive to engage in or avoid social activities, poses a significant challenge for those with schizophrenia. The trial aims to determine if buprenorphine can increase the desire for positive social interactions while decreasing the urge to avoid negative ones. Individuals with schizophrenia who are stable on their current treatment and have experienced low social engagement might be suitable candidates for this trial. Participants will receive either a placebo or buprenorphine in different sessions to assess which has a more positive effect on social motivation. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that low doses of buprenorphine are generally safe for people. Studies with healthy volunteers found that it can boost social motivation without causing major side effects. Although specific information about using low-dose buprenorphine for schizophrenia is limited, the FDA has approved the drug for treating opioid addiction and depression, suggesting reasonable safety.

This study is in phase 2, focusing mainly on the drug's safety and tolerability. Even though this trial targets schizophrenia, buprenorphine's approval for other conditions supports its safety.

For those considering joining a trial with buprenorphine, current data suggests it is relatively safe at low doses. However, discussing any concerns with the trial team or a healthcare professional is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

Researchers are excited about low-dose buprenorphine for schizophrenia because it offers a potentially new approach to treating this condition. Current treatments often involve antipsychotic medications that primarily target dopamine receptors, but buprenorphine works differently by acting on the opioid system. This unique mechanism could help address symptoms that don't fully respond to traditional therapies. Additionally, buprenorphine might provide benefits with fewer side effects, offering hope for improving the quality of life for individuals with schizophrenia.

What evidence suggests that low-dose buprenorphine might be an effective treatment for social motivation deficits in schizophrenia?

Research has shown that small amounts of buprenorphine can increase the desire for social interaction in healthy individuals. This trial aims to explore its potential benefits for people with schizophrenia who struggle with social motivation. Participants will receive either buprenorphine or a placebo in different sequences. Buprenorphine is a unique medication that encourages positive social interactions and helps avoid negative ones. Although it hasn't been specifically tested for social motivation in people with schizophrenia, early results are encouraging. Researchers hope buprenorphine could become the first medication to address social challenges in this condition. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

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

I have been diagnosed with schizophrenia.

I haven't been hospitalized or changed my medication in the last 6 months and don't have severe symptoms.

able to understand spoken English sufficiently to comprehend testing procedures

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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Effects of monthly buprenorphine extended-release ... Efficacy, safety, and retention outcomes will be published separately. ... schizophrenia patients. Schizophrenia Research, 118 (1) (2010), pp. 271-278.