From the Guidelines
Non-Opioid Treatments for Opioid Toxicity
Clonidine is a primary non-opioid treatment option for opioid toxicity, acting as an alpha-2 adrenergic agonist to alleviate withdrawal symptoms 1. The typical dose range for clonidine is 0.1-0.3 mg orally every 6-8 hours, which can be administered orally or transdermally. It's essential to start with small initial doses and carefully titrate to avoid orthostasis or hypotension 1.
- Other non-opioid treatments for opioid withdrawal include:
- Lofexidine, an FDA-approved medication for controlling opioid withdrawal symptoms 1
- Anti-emetics like promethazine to treat nausea and vomiting 1
- Benzodiazepines to reduce catecholamine release, alleviate muscle cramps, and anxiety 1
- Antidiarrheals such as loperamide to treat diarrhea, although caution is advised due to potential abuse and arrhythmia risks at high doses 1
- Tizanidine, less effective than clonidine but with a lower risk of hypotension 1
- Adjuvant medications like trazodone, tricyclic antidepressants, gabapentin, and mirtazapine, which can mitigate anxiety, insomnia, and irritability in the short term 1
From the FDA Drug Label
Supportive care may include atropine sulfate for bradycardia, intravenous fluids and/or vasopressor agents for hypotension and vasodilators for hypertension Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression, hypotension and/or coma; The administration of activated charcoal and/or cathartic may be beneficial.
The non-opioid treatments for opioid toxicity, such as clonidine, include:
- Supportive care: atropine sulfate for bradycardia, intravenous fluids and/or vasopressor agents for hypotension, and vasodilators for hypertension
- Activated charcoal and/or cathartic
- Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression, hypotension, and/or coma 2
From the Research
Non-Opioid Treatments for Opioid Toxicity
- Clonidine is a non-opioid α-2-adrenergic agonist that has been used to mitigate opioid withdrawal symptoms 3, 4, 5
- Lofexidine is another non-opioid α-2-adrenergic agonist that has been approved for the treatment of opioid withdrawal symptoms and has been shown to be effective in reducing withdrawal symptoms 3, 6
- Clonidine has been used as monotherapy for neonatal opioid withdrawal syndrome and has been shown to be effective in treating NOWS 4
- Lofexidine has been compared to clonidine in terms of efficacy and safety, and has been found to have fewer adverse effects than clonidine 3
- Clonidine has been used in a county jail setting to reduce opiate withdrawal symptoms in inmates, and has been found to be beneficial in reducing symptoms 5
Mechanism of Action
- The mechanism of action of clonidine and lofexidine involves agonism of α-2-adrenergic receptors, which can help to reduce the symptoms of opioid withdrawal 3, 6
- The use of clonidine and lofexidine can help to reduce the need for opioid-based treatments for opioid withdrawal, which can be beneficial in terms of reducing the risk of addiction and overdose 3, 4, 6
Efficacy and Safety
- Clonidine and lofexidine have been found to be effective in reducing opioid withdrawal symptoms, with lofexidine having fewer adverse effects than clonidine 3, 6
- Clonidine has been found to be effective in treating neonatal opioid withdrawal syndrome, with no significant differences in length of treatment or neurobehavioral performance compared to morphine 4
- Lofexidine has been found to be well-tolerated in clinical trials, with fewer adverse effects than clonidine 3, 6