Is buprenorphine/naloxone more effective than buprenorphine alone for treating opioid use disorder?

From the Guidelines

Buprenorphine/naloxone is generally preferred over buprenorphine alone for treating opioid use disorder in outpatient settings due to its safety feature that deters misuse by causing withdrawal symptoms if injected. The combination product contains naloxone, which has minimal effect when taken as prescribed sublingually, but can prevent misuse by causing withdrawal symptoms if injected 1. Buprenorphine alone is typically reserved for pregnant patients, those with documented naloxone allergy, or for observed administration in controlled settings.

Key Considerations

• Both buprenorphine/naloxone and buprenorphine alone work by partially activating opioid receptors to reduce cravings and withdrawal symptoms while blocking the effects of other opioids.
• The standard dosing range is 8-24 mg daily, with most patients stabilizing at 16 mg daily 1.
• Treatment should be individualized, with induction requiring careful timing after last opioid use to avoid precipitated withdrawal.
• Long-term maintenance therapy shows better outcomes than short-term use, and regular monitoring, counseling, and psychosocial support should accompany medication treatment for best results 1.
• The choice between formulations should be based on individual patient factors, risk of diversion, and treatment setting.

Recommendations

• Clinicians should offer or arrange evidence-based treatment, usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies, for patients with opioid use disorder 1.
• Physicians prescribing opioids in communities without sufficient treatment capacity for opioid use disorder should strongly consider obtaining a waiver to prescribe buprenorphine to treat patients with opioid use disorder 1.

From the FDA Drug Label

Clinical data on the safety and efficacy of buprenorphine were derived from studies of Buprenorphine Sublingual Tablets formulations, with and without naloxone, and from studies of sublingual administration of a more bioavailable ethanolic solution of buprenorphine The primary study comparison was to assess the efficacy of Buprenorphine and Naloxone Sublingual Tablets and Buprenorphine Sublingual Tablets individually against placebo sublingual tablet The percentage of thrice-weekly urine samples that were negative for non-study opioids was statistically higher for both Buprenorphine and Naloxone Sublingual Tablets and Buprenorphine Sublingual Tablets than for placebo sublingual tablets

The study directly compares Buprenorphine and Naloxone Sublingual Tablets and Buprenorphine Sublingual Tablets to a placebo, and finds both to be more effective than the placebo. However, it does not provide a direct comparison of the efficacy of Buprenorphine and Naloxone Sublingual Tablets to Buprenorphine Sublingual Tablets alone in terms of which is more effective for treating opioid use disorder.

• Key finding: Both formulations are more effective than placebo.
• Limitation: No direct comparison of the two formulations to each other. 2

From the Research

Comparison of Buprenorphine/Naloxone and Buprenorphine Alone

• The provided studies do not directly compare the effectiveness of buprenorphine/naloxone to buprenorphine alone for treating opioid use disorder 3, 4, 5, 6, 7.
• However, the studies suggest that buprenorphine/naloxone is a effective treatment for opioid use disorder, with benefits including ease of cessation and reduced use of illicit opioids 5, 7.
• One study found that buprenorphine/naloxone micro-dosing may offer a promising alternative approach for successful induction for individuals with opioid use disorder who desire treatment with buprenorphine/naloxone 3.
• Another study reported successful rotation from long-acting full agonist opioids to sublingual buprenorphine/naloxone using a microdosing approach, highlighting the potential benefits of this treatment approach 4.

Efficacy of Buprenorphine/Naloxone

• A study found that flexible take-home buprenorphine/naloxone is as effective as supervised methadone in reducing opioid use in individuals with prescription-type opioid use disorder 7.
• The study reported that the mean proportion of opioid-free urine drug screens was 24.0% in the buprenorphine/naloxone group and 18.5% in the methadone group, with a 5.6% adjusted mean difference 7.
• Another study reviewed scientific data concerning buprenorphine-induced changes in mu-opioid receptor availability and their relationship to clinical efficacy, suggesting that buprenorphine produces dose- and time-related alterations of mu-opioid receptor availability 6.

Treatment Outcomes

• A qualitative descriptive study found that participants who received buprenorphine/naloxone for the treatment of opioid use disorder reported an increased sense of citizenship and a desire to cease opioid use 5.
• The study identified factors influencing participants' decision-making in transferring between methadone and buprenorphine/naloxone, including sedation and opioid abstinence goals 5.