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.
Am J Drug Alcohol Abuse
; 43(1): 78-86, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-27712113
ABSTRACT
BACKGROUND:
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.OBJECTIVES:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinuclidinas
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Síndrome de Abstinência a Substâncias
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Hidroxizina
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Isoquinolinas
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article