Olanzapine for Post-Surgery Recovery

Overseen By John Guzzi, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Antipsychotics, Antihypertensives

Disqualifiers: Diabetes, Cardiovascular disease, Pregnancy, others

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

455 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether taking olanzapine before surgery can improve well-being the day after an operation with general anesthesia. Researchers aim to determine if it can also reduce post-hospital nausea, shorten recovery room stays, and decrease the need for painkillers. Women aged 18-50 scheduled for outpatient surgery with internet access might be suitable for this study. Participants will receive either olanzapine or a placebo (a pill with no active medicine) to compare outcomes. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial requires that you do not currently use anti-psychotic or antihypertensive medications. If you are taking these, you would need to stop before participating.

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

Research has shown that olanzapine is generally well-tolerated by patients, particularly for preventing post-surgery nausea. One study found it significantly reduced the risk of nausea and vomiting after surgery. Olanzapine is typically administered in low doses for a short duration, minimizing side effects.

For instance, in studies where it was given before surgery, olanzapine effectively reduced nausea without causing serious side effects. Most patients did not report major problems, and the medication was deemed safe for short-term use. However, like any medication, minor side effects such as drowsiness may occur. Overall, studies suggest olanzapine is a safe option for aiding recovery after surgery. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for post-surgery recovery?

Researchers are excited about using olanzapine for post-surgery recovery because it takes a novel approach compared to traditional pain management and recovery methods. Unlike standard care options that often rely on opioids and anti-inflammatory drugs to manage symptoms, olanzapine is primarily an antipsychotic medication that can help reduce nausea, vomiting, and anxiety, which are common after surgery. This unique mechanism of action not only targets the psychological aspects of recovery but also helps in minimizing the reliance on opioids, potentially reducing the risk of opioid-related side effects and dependencies.

What evidence suggests that olanzapine might be an effective treatment for post-surgery recovery?

Research shows that olanzapine can help reduce common post-surgery issues like nausea and vomiting. Studies have found that combining olanzapine with other anti-nausea medications significantly lowers the risk of these symptoms. Olanzapine is particularly effective at preventing nausea before it starts. In this trial, participants will receive either a 5 mg dose of olanzapine or a placebo. Previous studies found that a 10 mg dose worked better than a lower dose or no dose at all. However, the 5 mg dose may still aid recovery by reducing nausea and potentially enhancing the overall recovery experience. ^{1 2 6 7 8}

Who Is on the Research Team?

Jaime Hyman, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for women aged 18-50 who are scheduled for ambulatory surgery with general anesthesia and can access the internet. They must not have severe heart, liver, or blood pressure conditions, seizure disorders, certain eye diseases, Parkinson's disease or related dementia. Participants should not be on antipsychotics or antihypertensives, diabetic, allergic to olanzapine, pregnant or breastfeeding.

Inclusion Criteria

Provision of signed and dated informed consent form

I am willing and able to follow all study rules and be available for its duration.

I am scheduled for a surgery that requires me to be asleep.

Exclusion Criteria

I am currently taking medication for high blood pressure.

I cannot swallow pills.

I have an active tumor that affects my prolactin levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative

Participants receive either olanzapine or placebo prior to surgery

1 day

1 visit (in-person)

Post-operative

Participants' quality of recovery is assessed using the QoR-40 survey on postoperative days 1 and 2

2 days

2 visits (in-person)

Follow-up

Participants are monitored for post-discharge nausea and opioid consumption

24 hours post discharge

What Are the Treatments Tested in This Trial?

Interventions

• Olanzapine
• Placebo

Trial Overview The study tests if taking Olanzapine (5 mg) before surgery improves recovery quality compared to a placebo. Recovery is measured by a survey on postoperative days 1 and 2. The trial also looks at nausea after discharge, opioid use and how long patients stay in the recovery room.

How Is the Trial Designed?

Group I: Olanzapine Experimental Treatment 1 Intervention

olanzapine oral tablet, 5mg, once prior to surgery

Group II: Placebo Placebo Group 1 Intervention

placebo oral tablet once prior to surgery

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

Approved in United States as Zyprexa for:

• Schizophrenia
• Bipolar disorder
• Depression
• Nausea and vomiting associated with chemotherapy
• Off-label use for cancer cachexia and anorexia

Approved in European Union as Zyprexa for:

• Schizophrenia
• Bipolar disorder
• Depression
• Nausea and vomiting associated with chemotherapy

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Published Research Related to This Trial

In a study of 140 adult female patients undergoing ambulatory surgery, a single preoperative dose of olanzapine significantly reduced the incidence of postdischarge nausea and vomiting by about 60% compared to placebo.

While olanzapine effectively decreased nausea and vomiting, it was associated with a slight increase in sedation levels, indicating a trade-off between efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine for the Prevention of Postdischarge Nausea and Vomiting after Ambulatory Surgery: A Randomized Controlled Trial. Hyman, JB., Park, C., Lin, HM., et al.[2020]

Intramuscular olanzapine is effective for treating acute agitation in patients with schizophrenia or bipolar mania, showing at least equal efficacy to intramuscular haloperidol or lorazepam, with a faster onset of action based on evidence from three well-designed trials.

The use of intramuscular olanzapine is generally well tolerated, with a low incidence of extrapyramidal symptoms and minimal impact on heart health, making it a promising option for managing agitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intramuscular olanzapine: a review of its use in the management of acute agitation. Wagstaff, AJ., Easton, J., Scott, LJ.[2022]

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]

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 was administered to three elderly patients experiencing psychosis due to post-operative delirium, but the study could not definitively conclude its efficacy in reversing delirium since this condition often resolves on its own.

The case reports suggest that olanzapine may have potentially reduced the duration of psychotic symptoms, highlighting its pharmacological benefits, convenient dosing, and side effects profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with olanzapine in the course of post-operative delirium associated with psychosis in geriatric patients: A report of three cases. Gazula, HR.[2014]

In a study of 26 patients with acute olanzapine poisoning, common symptoms included tachycardia (85%), psychomotor agitation (81%), and coma (54%), indicating significant effects on the circulatory and central nervous systems.

Despite the severity of symptoms, including prolonged consciousness disturbances lasting up to 6 days, fatal outcomes from olanzapine overdose are rare, suggesting a relatively favorable safety profile in acute cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The clinical picture of acute olanzapine poisonings]. Ciszowski, K., Sein Anand, J., Wilimowska, J., et al.[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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10972821/

Olanzapine as a prophylactic antiemetic for preventing ... Olanzapine is identified as a potentially effective prophylactic antiemetic. Olanzapine reduces the incidence of postoperative nausea and vomiting.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39865665/

Effect of different doses of oral olanzapine to prevent ... Conclusion: Olanzapine 10 mg had a higher effect than the lower concentration of 5 mg or control in reducing the incidence of postoperative ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0885392425000430

Olanzapine for the Prevention of Postoperative Nausea ... Olanzapine potentially decreases PONV incidence rates, particularly when combined with traditional antiemetics, indicating its pivotal role in PONV prevention.

4. clinicaltrial.be clinicaltrial.be/en/details/187883?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

The Impact of Preoperative Olanzapine on Quality of Recov... Because olanzapine has been shown to be an effective drug for PDNV prevention, but carries the risk of sedation, this study seeks to identify if ...

5. withpower.com withpower.com/trial/phase-2-nausea-2023-4a0e7

Olanzapine for Post-Surgery Recovery Trial Overview The study tests if taking Olanzapine (5 mg) before surgery improves recovery quality compared to a placebo. Recovery is measured by a survey on ...

6. associationofanaesthetists-publications.onlinelibrary.wiley.com associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.16081

Olanzapine as an add‐on, pre‐operative anti‐emetic drug for ... The primary outcome was the incidence of postoperative nausea or vomiting in the first 24 h after surgery. In total, 100 patients were enrolled; ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05676294

The Impact of Preoperative Olanzapine on Quality ... The secondary objectives of this study are to determine whether there are differences in quality of recovery on postoperative day 2, presence of post-discharge ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10625498/

Comparative Safety Analysis of Oral Antipsychotics for In ... Among older surgical patients who were prescribed an oral low-to-moderate dose antipsychotic drug, the risks of in-hospital death, cardiac arrhythmia events, ...