Palonosetron and hydroxyzine pre-treatment reduces the objective signs of experimentally-induced acute opioid withdrawal in humans: a double-blinded, randomized, placebo-controlled crossover study
| Autor: | Ellen M. Encisco, Jeffrey J Yu, Larry F. Chu, Gary Peltz, J. David Clark, Matthew J. Erlendson, Nicole D'Arcy, Lorena Rincon-Cruz |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Quinuclidines medicine.medical_treatment Medicine (miscellaneous) Physical dependence (+)-Naloxone Placebo Article 03 medical and health sciences Young Adult 0302 clinical medicine Double-Blind Method Medicine Humans Hydroxyzine Cross-Over Studies Morphine business.industry Naloxone Palonosetron Drug Synergism Isoquinolines Crossover study Healthy Volunteers Substance Withdrawal Syndrome Psychiatry and Mental health Clinical Psychology 030104 developmental biology Opioid Anesthesia Antihistamine medicine.symptom business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | The American journal of drug and alcohol abuse. 43(1) |
| ISSN: | 1097-9891 |
| Popis: | Treatments for reducing opioid withdrawal are limited and prone to problematic side effects. Laboratory studies, clinical observations, and limited human trial data suggest 5-HT3-receptor antagonists and antihistamines may be effective.This double-blind, crossover, placebo-controlled study employing an acute physical dependence model evaluated whether (i) treatment with a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal symptoms, and (ii) co-administration of an antihistamine (hydroxyzine) would enhance any treatment effect.At timepoint T = 0, healthy (non-opioid dependent, non-substance abuser) male volunteers (N = 10) were pre-treated with either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg) and hydroxyzine PO (100 mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10 mg/70kg). At T = 165, 10 mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15.Comparison of average baseline OOWS scores with OOWS scores obtained 15 minutes after naloxone was significant (p = 0.0001). Scores from 15 minutes post-naloxone infusion showed significant differences in OOWS scores between treatment groups: placebo, 3.7 ± 2.4; palonosetron, 1.5 ± 0.97; and palonosetron with hydroxyzine, 0.2 ± 0.1333.Pretreatment with palonosetron significantly reduced many signs of experimentally-induced opioid withdrawal. Co-administration with hydroxyzine further reduced opioid withdrawal severity. These results suggest that 5-HT3 receptor antagonists, alone or in combination with an antihistamine, may be useful in the treatment of opioid withdrawal. |
| Databáze: | OpenAIRE |
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