Is there any evidence for using an atypical antipsychotic other than olanzapine to prevent chemotherapy-induced nausea and vomiting?

Comment by InpharmD Researcher

A comprehensive literature search identified no evidence supporting the use of atypical antipsychotics for the treatment of chemotherapy-induced nausea and vomiting (CINV) other than olanzapine. Similarly, the 2025 NCCN antiemesis guidelines do not address or recommend any alternative atypical antipsychotics beyond olanzapine. One combined case series and case report described the use of risperidone for nausea and vomiting in cancer patients; however, this was limited to the management of opioid-induced nausea and vomiting rather than CINV (Tables 1 and 2).

chemotherapy induced nausea and vomiting AND atypical antipsychotic; CINV and atypical antipsychotic

Background

The 2025 National Comprehensive Care Network (NCCN) antiemesis guidelines outline treatment recommendations for the prevention and management of chemotherapy-induced nausea and vomiting (CINV) across high-, moderate-, and low-emetogenic chemotherapy regimens. Notably, olanzapine is the only atypical antipsychotic specifically addressed by the expert panel. [1]

References: [1] National Comprehensive Care Network (NCCN). Antiemesis. Version 2.2025. Updated May 12, 2025. Accessed January 8, 2026. https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Is there any evidence for using an atypical antipsychotic other than olanzapine to prevent chemotherapy-induced nausea and vomiting?

Level of evidence

D - Case reports or unreliable data  Read more→


Please see Tables 1-2 for your response.

A Retrospective Chart Review of the Antiemetic Effectiveness of Risperidone in Refractory Opioid-Induced Nausea and Vomiting in Advanced Cancer Patients

Design

Retrospective, single-center, chart review

N= 20

Objective

To examine whether risperidone is useful for opioid-induced nausea and vomiting in advanced cancer patients

Study Groups

Risperidone (n= 20)

Inclusion Criteria

No medication other than opioids was started or increased before nausea and vomiting occurred, no physical and laboratory cause other than opioids was found before or after nausea and vomiting occur

Exclusion Criteria

Gastrointestinal stasis according to the clinical features

Methods

Pharmacy and medical records of patients who received risperidone for the treatment of refractory opioid-induced nausea and vomiting that had not been controlled by previous antiemetic treatments were identified. Risperidone was given in doses of 1 mg once a day to all patients at bedtime. 

The effect of treatment on nausea and vomiting was evaluated based on the following criteria: a complete response (CR) to the treatment of nausea or vomiting was defined as a lack of nausea or vomiting on the following day. A partial response (PR) was identified as a reduction in nausea or vomiting within three days. No response was defined as a lack of change in nausea or vomiting.

Duration

March 2004 to July 2006

Outcome Measures

 Antiemetic effectiveness of risperidone in refractory opioid-induced nausea and vomiting 

Baseline Characteristics

  

Risperidone (n= 20)

Age, years

 49.2 ± 12.8    

Female

70%    

Most common malignancies

Breast cancer

Gastric cancer

Osteosarcoma

 

25%

15%

10%     

Results

Gender

Age

Diagnosis

Opioids (mg/day)

Antiemetics (mg/day)

 Nausea Vomiting

F

 47 Breast cancer CO (40), NM (5)  PP (15), MP (15)  CR CR

F

 28 Osteosarcoma CO (50) PP (15) PR CR 

F

 34 Endometrial cancer CM (120), NM (15) PP (15) CR -

F

 56 Gastric cancer FP (0.6), NM (10) PP (15) CR -

M

 19 Osteosarcoma MI (96) HI (5) CR -

M

 56 Esophageal cancer FP (4.8), NM (30) PP (5), BZ (3) CR -

M

 56 Prostatic cancer FP (6), MS (30) PP (15), BM (2), HP (0.75) CR PR

M

 69 Esophageal cancer FP (3.6), MS (10) DO (120), BM (4) CR -
F 51 Pancreatic cancer CO (60) PP (15) PR CR
F 48 Breast cancer FP (3.6), NM (30) PP (15) PR NR
M 59 Tongue cancer CM (540) PP (15) PR PR
F 58 Lung cancer FP (1.2) PP (15) PR CR
F 42 Breast cancer FP (6), CO (180) PP (15), DI (120) PR PR
F 51 Gastric cancer CM (20), NM (5) PP (15), MP im (10) PR -
F 67 Cervical cancer CM (60) PP (15) PR -
F 64 Breast cancer CO (75) MP (30) CR CR
F 50 Breast cancer CO (10), NM (5) PP (15) CR CR
M 55 Gastric cancer FP (0.6), MS (20) PP (15), MP iv (20) PR -
F 40 Vulvar sarcoma FP (0.6) DO (30), DH (120) CR CR
F 33 Vaginal cancer CO (20), NM (5) MP (30), PP (15) PR -

BM=betamethasone; BZ=bromazepam; CM=controlled-release morphine; CO=controlled-release oxycodone; CR=complete response; DH=diphenhydramine; DD=domperidone; FP=fentanyl patch; HI=haloperidol injection; HP=haloperidol; MP=metoclopramide; MI=morphine injection; MS=morphine suppository; NM=normal-release morphine; NR=no response; PP=prochlorperazine; PR=partial response; —=no symptom. 

Complete response was observed in 50% of patients (10/20) for nausea and 64% (7/11) for vomiting.

Adverse Events

Common Adverse Events: sedation (n=2) was documented as an adverse effect.

Study Author Conclusions

Risperidone may be an effective antiemetic drug in the treatment of refractory opioid-induced nausea and vomiting in advanced cancer patients. These findings require replication and confirmation in a larger, prospective trial.

InpharmD Researcher Critique

The results of the study are subject to limitations inherent to its small sample size, single-center design, and retrospective nature. Other side effects associated with risperidone such as its effect on hyperprolactinemia were not examined in this study. Since the focus of the study was on patients with opioid-induced nausea and vomiting, it is uncertain if the antiemetic data may be applicable to other patient populations. 
References:
[1] Okamoto Y, Tsuneto S, Matsuda Y, et al. A retrospective chart review of the antiemetic effectiveness of risperidone in refractory opioid-induced nausea and vomiting in advanced cancer patients. J Pain Symptom Manage. 2007;34(2):217-222. doi:10.1016/j.jpainsymman.2006.10.020

A Retrospective Chart Review of the Antiemetic Effectiveness of Risperidone in Refractory Opioid-Induced Nausea and Vomiting in Advanced Cancer Patients

Design

 Case report

Case Presentation

 A 47-year-old female with breast cancer underwent surgery. After 6 courses of postoperative chemotherapy, she developed bone metastasis and local recurrence. She received doxifluridine (two capsules twice a day), incadronate (10 mg intravenously), and radiation therapy at a total dose of 40 Gy to Th12-L5. For pain management, a diclofenac suppository at 50 mg twice a day was used. Chemotherapy with docetaxel (110 mg/day on days 1, 8, and 15) and capecitabine (1,800 mg/day for 21 days) were administered, but because the pain was not alleviated, oxycodone (controlled-release tablet, 5 mg orally twice daily) was initiated, and the oxycodone dose was increased (10 mg twice a day) to control the pain. The patient subsequently developed nausea and vomiting, which did not subside with a domperidone suppository (60 mg) and metoclopramide (5 mg three times a day). Nausea and vomiting were alleviated with additional prochlorperazine tablets (5 mg three times a day). When oxycodone was increased to 20 mg twice daily, the patient experienced persistent feelings like "car sickness," vomiting, and difficulty eating. Prochlorperazine was discontinued, and oral administration of risperidone tablet at 1 mg once a day at bedtime was started. The next day, her nausea and vomiting resolved, she could eat, and her sleep improved. The pain subsided with an increase in the dosage of oxycodone to 50 mg/day and normal-release morphine at 10 mg four times a day.

Study Author Conclusions

Risperidone may be an effective antiemetic drug in the treatment of refractory opioid-induced nausea and vomiting in advanced cancer patients. These findings require replication and confirmation in a larger, prospective trial.
References:
[1] Okamoto Y, Tsuneto S, Matsuda Y, et al. A retrospective chart review of the antiemetic effectiveness of risperidone in refractory opioid-induced nausea and vomiting in advanced cancer patients. J Pain Symptom Manage. 2007;34(2):217-222. doi:10.1016/j.jpainsymman.2006.10.020