From the Guidelines
Non-opioid treatments for opioid toxicity are preferred and include medications such as α2-adrenergic agonists, antiemetics, benzodiazepines, and antidiarrheals.
Non-opioid treatment options
- α2-adrenergic agonists, such as clonidine and lofexidine, can be used to treat symptomatic patients with nonhypotensive opioid withdrawal 1
- Antiemetics, such as promethazine, can be used to treat nausea and vomiting 1
- Benzodiazepines can help reduce catecholamine release during withdrawal and alleviate muscle cramps, anxiety, and other symptoms 1
- Antidiarrheals, such as loperamide, can be used to treat diarrhea 1
Additional considerations
- Medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies is recommended for patients with opioid use disorder 1
- Naltrexone can also be used as medication-assisted treatment for opioid use disorder in nonpregnant adults 1
- Clinicians should establish treatment goals with patients, consider how opioids will be discontinued if benefits do not outweigh risks, and communicate with mental health professionals managing the patient to discuss the patient’s needs and prioritize patient goals 1
From the Research
Non-Opioid Treatments for Opioid Toxicity
- Non-opioid agents for managing acute opioid withdrawal can be divided into four broad mechanistic categories: α-adrenergic receptor agonists, N-methyl-d-aspartate (NMDA) antagonists, gamma-aminobutyric acid (GABA) modulators, and serotonergic agents 2
- α-adrenergic receptor agonists, such as clonidine and lofexidine, have the best evidence of efficacy as alternative agents for acute opioid withdrawal 2
- Clonidine has been shown to significantly attenuate the opiate withdrawal syndrome in both animals and humans 3, 4
- Lofexidine, a structural analogue of clonidine, may be safer and more effective as an opiate detoxification treatment, with similar withdrawal-suppressing actions but less hypotension and sedation 3, 4
Clonidine and Lofexidine as Non-Opioid Treatments
- Clonidine is a reasonably safe, specific, and effective agent for detoxifying opiate addicts, but its use must be individualized and closely supervised due to varying sensitivity to its sedative, hypotensive, and withdrawal-suppressing effects 3, 4
- Lofexidine may be more suitable for outpatient treatment due to its lack of sedative and hypotensive side effects 4
- Both clonidine and lofexidine can be used as transitional treatments between opiate dependence and induction onto the opiate antagonist naltrexone 3, 4
Safety and Efficacy of Non-Opioid Treatments
- Clonidine overdose can cause persistent but not life-threatening clinical effects, including mild central nervous system depression and bradycardia 5
- Naloxone may not be effective in reversing clonidine-induced toxicity, and its use may be associated with opioid withdrawal symptoms 5, 6
- High-dose naloxone may be more likely to cause opioid withdrawal symptoms and reversal of opioid toxicity compared to low-dose naloxone 6