Olanzapine for Opioid Use Disorder

Overseen By Joseph Arthur, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antipsychotics

Disqualifiers: Substance use disorders, Psychiatric diagnoses, Diabetes, Cardiac disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Unknown

Duration: 4 weeks

87 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether the antipsychotic medication olanzapine can reduce cravings for opioids in individuals with opioid use disorder. Participants will receive either a placebo, a lower dose of olanzapine, or a gradually increasing dose over four weeks. It suits individuals with cancer pain who are currently using opioids and have exhibited behaviors of opioid misuse. The trial aims to discover a new method to manage opioid cravings and potentially enhance treatment options for opioid use disorder. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

If you are currently taking any antipsychotic medications, you will need to stop them to participate in this trial. The protocol does not specify about other medications, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that olanzapine has been used safely in various studies. For example, one study found that olanzapine might help with symptoms of opioid withdrawal, suggesting it could be beneficial and safe for individuals dealing with opioid issues. Another study found that olanzapine reduced aggression in people with substance use problems, without major safety concerns.

Olanzapine is already FDA-approved for other uses, indicating it has passed safety checks for those conditions. While each new use requires its own safety tests, this background can provide some confidence in its safety. However, discussing personal health concerns with a healthcare provider before joining a trial is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for opioid use disorder?

Researchers are excited about using olanzapine for opioid use disorder because it offers a fresh approach compared to typical treatments, such as methadone or buprenorphine, which primarily target opioid receptors. Olanzapine, an antipsychotic, works differently by affecting dopamine and serotonin receptors in the brain, which might help reduce cravings and stabilize mood. This unique mechanism provides a new angle in tackling the condition, potentially offering relief for patients who do not fully respond to existing therapies. Additionally, the trial explores different dosing strategies, which could optimize its effectiveness and minimize side effects.

What evidence suggests that olanzapine could be effective for opioid use disorder?

Research has shown that olanzapine might help reduce cravings for opioids. One study found that olanzapine improved issues like appetite, sleep, and restlessness better than a similar medication during opioid withdrawal. Another study found that people taking olanzapine stayed in treatment longer compared to those on a different medication. Additionally, olanzapine is considered a safe and effective option for managing opioid withdrawal symptoms. In this trial, participants will be assigned to different arms, with some receiving varying doses of olanzapine and others receiving a placebo. These findings suggest that olanzapine could be a promising treatment for opioid use disorder. ^{2 3 4 6 7}

Who Is on the Research Team?

Joseph Arthur, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients who are experiencing pain due to cancer and have been prescribed opioids. It's aimed at those who might be struggling with opioid cravings or misuse.

Inclusion Criteria

I have been on opioid pain medication for 30 days or more.

Active use of opioids within the past 7 days

Opioid misuse behavior (COMM score ≥ 9/68)

Exclusion Criteria

History of formal psychiatric diagnoses (e.g. bipolar disorder, schizophrenia, major depressive disorder, or anorexia nervosa)

I am allergic to or cannot take olanzapine.

I am currently taking antipsychotic medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either olanzapine or placebo for 4 weeks to assess its effect on opioid craving and misuse

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 weeks

Monthly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Olanzapine

Trial Overview The study tests if olanzapine, an antipsychotic medication, can reduce the craving for opioids in these patients. Participants will either receive olanzapine or a placebo without knowing which one they get.

How Is the Trial Designed?

Group I: Arm 2 Experimental Treatment 1 Intervention

Participants will take the lower dose of olanzapine every day for 4 weeks.

Group II: Arm 1 Experimental Treatment 1 Intervention

Participants will take a lower dose of olanzapine every day for Days 1-7 and then a higher dose every day for the next 3 weeks

Group III: Arm 3 Placebo Group 1 Intervention

Participants will take a placebo every day for 4 weeks.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a randomized, double-blind, placebo-controlled trial involving 48 cocaine-dependent individuals over 16 weeks, olanzapine did not show any significant efficacy compared to placebo in reducing cocaine use, as measured by weekly urine screens.

Both groups reported side effects, but there were no unexpected adverse effects, indicating that while olanzapine was safe, it was ineffective for treating cocaine dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine in cocaine dependence: a double-blind, placebo-controlled trial. Hamilton, JD., Nguyen, QX., Gerber, RM., et al.[2018]

In a 7-week trial involving 60 treatment-resistant schizophrenia patients, those with a history of substance abuse showed similar overall improvement in symptoms when treated with olanzapine compared to those without a history of abuse.

Despite a higher tendency for tardive dyskinesia in substance-abusing patients, olanzapine treatment did not lead to increased adverse effects, suggesting it is a safe and effective option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine response in treatment-refractory schizophrenic patients with a history of substance abuse. Conley, RR., Kelly, DL., Gale, EA.[2019]

In a study involving 21 patients in a methadone maintenance program, treatment with olanzapine led to a decrease or cessation of cocaine use in 53.2% of participants, indicating its potential efficacy in treating cocaine abuse.

Olanzapine was well tolerated and did not cause any withdrawal symptoms or pharmacokinetic interactions with methadone, suggesting it can be safely used alongside methadone without affecting its levels in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Olanzapine efficacy in the treatment of cocaine abuse in methadone maintenance patients. Interaction with plasma levels]. Baño, MD., Micó, JA., Agujetas, M., et al.[2018]

In a study of 92 adults on methadone treatment, 30% reported a lifetime history of non-medical use (NMU) of olanzapine, primarily for self-medication to relieve anxiety and aid sleep, with some using it for recreational purposes.

A small percentage (12%) reported NMU in the past month, and among those assessed, 50% were identified as high-risk users, indicating a need for healthcare providers to be vigilant about the potential for NMU in patients with addiction histories.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-medical use of olanzapine by people on methadone treatment. James, PD., Fida, AS., Konovalov, P., et al.[2023]

Olanzapine, an atypical antipsychotic used to treat schizophrenia, can cause serious side effects such as increased appetite and weight gain, which are common.

This report highlights a rare case of diabetic ketoacidosis occurring in a 16-year-old girl during olanzapine treatment, indicating that this severe adverse effect can also manifest in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetic ketoacidosis associated with olanzapine in an adolescent patient. Selva, KA., Scott, SM.[2018]

In a 12-week study involving 61 heroin-dependent patients with schizophrenia spectrum disorders, those treated with olanzapine (91.4% retention) had significantly better treatment retention compared to those treated with haloperidol (50%).

Patients receiving olanzapine also showed greater improvement in psychopathology symptoms and higher rates of substance abuse remission (78.13% full remission) compared to those on haloperidol (46.1% full remission), suggesting olanzapine may be more effective for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of olanzapine with opioid-agonists in the treatment of heroin-addicted patients affected by comorbid schizophrenia spectrum disorders. Gerra, G., Di Petta, G., D'Amore, A., et al.[2019]

Olanzapine has been authorized for treating schizophrenia, but its specific effects on positive or negative symptoms have not been proven due to a lack of relevant trials.

While olanzapine shows similar overall efficacy to haloperidol and does not outperform risperidone, it has fewer neurological side effects than haloperidol; however, it can cause weight gain and other adverse effects, necessitating ongoing monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine. Keep an eye on this neuroleptic. [2022]

Olanzapine (ZYPREXA) has been shown to be an effective and well-tolerated maintenance therapy for preventing relapse in patients with bipolar I disorder, based on four randomized controlled trials lasting between 47 to 78 weeks.

The medication is effective in preventing relapse after manic or mixed episodes, including in patients with rapid cycling, although it is important to monitor for potential side effects like weight gain and metabolic issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine - relapse prevention following mania. Dando, S., Tohen, M.[2018]

In a clinical safety review involving 2500 patients treated with olanzapine for acute schizophrenia, the overall discontinuation rate was low, indicating good tolerability of the medication.

While olanzapine was associated with some significant adverse effects such as somnolence, weight gain, and elevated liver enzymes, it showed minimal risk for parkinsonism, akathisia, and no cases of hematotoxicity, making it a relatively safe option compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of olanzapine. Beasley, CM., Tollefson, GD., Tran, PV.[2018]

The study evaluated the bioavailability of olanzapine in three formulations, including ALKS 3831, which combines olanzapine with samidorphan to reduce weight and metabolic side effects, involving 48 healthy volunteers.

Results showed that the bioavailability of olanzapine in ALKS 3831 is equivalent to that in standard olanzapine formulations, indicating that ALKS 3831 can provide the therapeutic benefits of olanzapine without compromising its absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of Olanzapine Given in Combination With Samidorphan as a Bilayer Tablet (ALKS 3831) Compared With Olanzapine-Alone Tablets: Results From a Randomized, Crossover Relative Bioavailability Study. Sun, L., McDonnell, D., Liu, J., et al.[2020]

Olanzapine effectively reduces hyperlocomotion and the rewarding effects of morphine in rodents without causing motor dysfunction, suggesting its potential to mitigate the abuse potential of μ-opioids.

The study indicates that olanzapine can attenuate the psychoactive effects of morphine at doses that do not impair motor coordination, highlighting its safety and efficacy in preventing opioid-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine suppresses the rewarding and discriminative stimulus effects induced by morphine. Torigoe, K., Mori, T., Shibasaki, M., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11843756/

A pharmacovigilance study of olanzapine/samidorphan based ... This study included 86 reports of AEs associated with the OLZ/SAM and 4,678 reports related to OLZ. In terms of frequency of OLZ/SAM-related AEs ...

2. psychiatry-psychopharmacology.com psychiatry-psychopharmacology.com/en/could-olanzapine-be-a-new-choice-for-the-treatment-of-opioid-withdrawal-13867

Could olanzapine be a new choice for the treatment of ... Olanzapine compared to chlorpromazine in a 21-day study, was more effective in appetite, sleep, restlessness, agitation and craving.

3. withpower.com withpower.com/trial/olanzapine-for-opioid-use-disorder-662e6

Olanzapine for Opioid Use Disorder A study found that olanzapine helped heroin-dependent patients with schizophrenia spectrum disorders stay in treatment longer compared to another antipsychotic, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02643355

Utility of Olanzapine in the Treatment of Opioid Withdrawal ... The hypothesis of this study is that olanzapine is a safe and efficacious option when compared to clonidine for the treatment of opioid withdrawal in the ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0278584606001850

Effects of olanzapine on aggressiveness in heroin ... Among the completers, 69.3% achieved early full substance abuse remission, while 30.7% achieved partial substance abuse remission, with no significant ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10094996/

Quetiapine and olanzapine misuse prevalence in a US ... Results. Among 1843 total respondents, 229 had a history of quetiapine or olanzapine use. Misuse prevalence was estimated to be 6.3% (95% CI: 5 ...

7. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-urges-caution-about-withholding-opioid-addiction-medications

FDA urges caution about withholding opioid addiction ... The combined use of these drugs increases the risk of serious side effects; however, the harm caused by untreated opioid addiction can outweigh ...