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Ondansetron Does Not Reduce Withdrawal in Patients With Physical Dependence on Chronic Opioid Therapy

Chu, Larry, F.; Sun, John; Clemenson, Anna; Erlendson, Matthew, J.; Rico, Tom; Cornell, Erika; Obasi, Hannah; Sayyid, Zahra, N.; Encisco, Ellen, M.; Yu, Jeff; Gamble, Jamison, G.; Carroll, Ian; Clark, J., David

doi: 10.1097/ADM.0000000000000321
Original Research

Objectives: Individuals taking opioids for an extended period of time may become physically dependent, and will therefore experience opioid withdrawal should they stop taking the medication. Previous work in animal and human models has shown that the serotonin (5-HT3) receptor may be implicated in opioid withdrawal. In this study, we investigated if ondansetron, a 3-receptor antagonist">5-HT3-receptor antagonist, could reduce the symptoms of opioid withdrawal after chronic opioid exposure in humans.

Methods: In this double-blinded, randomized, crossover study, 33 chronic back pain patients (N = 33) were titrated onto sustained-release oral morphine for 30 days. After titration, participants attended 2 study sessions, 1 week apart, in which opioid withdrawal was induced with intravenous naloxone, with or without 8 mg intravenous ondansetron pretreatment. Opioid withdrawal symptoms were assessed by a blinded research assistant (objective opioid withdrawal score [OOWS]) and by the research participant (subjective opioid withdrawal score [SOWS]).

Results: Clinically significant signs of withdrawal were observed during both the ondansetron (ΔOOWS = 3.58 ± 2.22, P < 0.0001; ΔSOWS = 12.48 ± 11.18, P < 0.0001) and placebo sessions (ΔOOWS = 3.55 ± 2.39, P < 0.0001; ΔSOWS = 12.21 ± 10.72, P < 0.0001), but no significant differences were seen between the treatment sessions in either the OOWS or SOWS scores.

Conclusion: We hypothesized that ondansetron would reduce opioid withdrawal symptoms in human subjects, but found no difference in withdrawal severity between ondansetron and placebo sessions. These findings suggest that more investigation may be necessary to determine if 5-HT3-receptor antagonists are suitable treatment options for opioid withdrawal.

Stanford University School of Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford (LFC, JS, AC, MJE, TR, EC, HO, ZNS, EME, JY, JGG, IC); and Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA (JDC).

Send correspondence to Larry F. Chu, MD, MS, Department of Anesthesiology, Stanford University School of Medicine, 300 Pasteur Drive, Grant Building Room S268C, Stanford, CA 94305. E-mail:

Received 1 November, 2016

Accepted 31 March, 2017

Funding: This work was supported by a grant from the National Institutes of Health (NIH, 1 RO1 DA029078-01A1), and the Stanford University School of Medicine Department of Anesthesiology.

The authors report no conflicts of interest.

© 2017 American Society of Addiction Medicine