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Opioid antagonists with minimal sedation for opioid withdrawal

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Abstract

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Background

Managed withdrawal is a necessary step prior to drug‐free treatment or as the end point of long‐term substitution treatment.

Objectives

To assess the effectiveness of opioid antagonists in combination with minimal sedation to manage opioid withdrawal.

Search methods

We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2008), MEDLINE (January 1966‐July 2008), EMBASE (January 1985‐2008 Week 31), PsycINFO (1967 to 7 August 2008) and reference lists of articles.

Selection criteria

Controlled studies of interventions involving the use of opioid antagonists in combination with minimal sedation to manage withdrawal in opioid‐dependent participants compared with other approaches or different opioid antagonist regimes.

Data collection and analysis

One author assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all authors.

Main results

Nine studies (6 randomised controlled trials), involving 837 participants, met the inclusion criteria for the review.

The quality of the evidence is low, but suggests that withdrawal induced by opioid antagonists in combination with an adrenergic agonist is more intense than withdrawal managed with clonidine or lofexidine alone, while the overall severity is less. Delirium may occur following the first dose of opioid antagonist, particularly with higher doses (> 25mg naltrexone).

In some situations antagonist‐induced withdrawal may be associated with significantly higher rates of completion of treatment, comp[ared to withdrawal managed primarily with adrenergic agonists. However, this outcome has not been produced consistently, and the extent of any benefit is highly uncertain.

Authors' conclusions

The use of opioid antagonists combined with alpha2‐adrenergic agonists is a feasible approach to the management of opioid withdrawal. However, it is unclear whether this approach reduces the duration of withdrawal or facilitates transfer to naltrexone treatment to a greater extent than withdrawal managed primarily with an adrenergic agonist.

A high level of monitoring and support is desirable for several hours following administration of opioid antagonists because of the possibility of vomiting, diarrhoea and delirium.

Further research is required to confirm the relative effectiveness of antagonist‐induced regimes, as well as variables influencing the severity of withdrawal, adverse effects, the most effective antagonist‐based treatment regime, and approaches that might increase retention in subsequent naltrexone maintenance treatment.

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Plain language summary

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It is feasible to use opioid antagonists with minimal sedation to manage opioid withdrawal but the value of the approach is uncertain.

Opioid antagonists induce withdrawal by displacing opioids from their receptors. Adrenergic agonists, acting through non‐opioid mechanisms, can reduce withdrawal symptoms induced by antagonists. The use of these substances in combination is a feasible approach to the management of opioid withdrawal, but evidence on the effectiveness of the approach is of low quality leaving uncertainty about its value.