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

Trial Summary

What is the purpose of this trial?

The primary objective of this phase 2 randomized controlled trial is to determine whether the pre-operative administration of olanzapine (5 mg PO) improves quality of recovery (assessed by the Quality of Recovery-40 (QoR-40) survey) on postoperative day 1 in patients having ambulatory surgery with general anesthesia. 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 nausea, presence of severe post-discharge nausea, recovery room length of stay and opioid consumption in patients who receive the study drug versus placebo.

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.

What evidence supports the effectiveness of the drug Olanzapine for post-surgery recovery?

Olanzapine is known to be effective in managing symptoms of schizophrenia and bipolar disorder, including preventing relapse in bipolar disorder and managing acute agitation. While these conditions are different from post-surgery recovery, the drug's ability to manage agitation and its rapid action might suggest potential benefits in a post-surgery context, although direct evidence is lacking. ^{1 2 3 4 5}

Is olanzapine generally safe for humans?

Olanzapine is generally well-tolerated, but it can cause weight gain and metabolic issues, and in rare cases, it may lead to serious conditions like diabetic ketoacidosis (a severe diabetes complication). It may also cause elevated liver enzymes, increased blood pressure, and changes in heart rhythm, so monitoring is important. ^{1 2 3 4 6}

How does the drug olanzapine differ from other treatments for post-surgery recovery?

Olanzapine is unique for post-surgery recovery because it is primarily used to prevent postdischarge nausea and vomiting, which is a common issue not well-addressed by current treatments. Unlike typical anti-nausea medications, olanzapine is an atypical antipsychotic that may also help with post-operative delirium, offering a broader range of benefits in the recovery process. ^{1 2 3 6 7}

Research Team

Jaime Hyman, MD

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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 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]

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]

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]

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]

References

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

Diabetic ketoacidosis associated with olanzapine in an adolescent patient. [2018]

2. Canada pubmed.ncbi.nlm.nih.gov

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

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

Olanzapine - relapse prevention following mania. [2018]

4. Poland pubmed.ncbi.nlm.nih.gov

[The clinical picture of acute olanzapine poisonings]. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Intramuscular olanzapine: a review of its use in the management of acute agitation. [2022]

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

Olanzapine for the Prevention of Postdischarge Nausea and Vomiting after Ambulatory Surgery: A Randomized Controlled Trial. [2020]

7. England 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. [2014]