## Maintenance Therapy in Opioid Use Disorder **Key Point:** Methadone is the gold-standard, first-line drug of choice for long-term maintenance therapy in opioid use disorder. ### Mechanism and Rationale Methadone is a synthetic, long-acting full mu-opioid agonist that: - Has a half-life of 24–36 hours, allowing once-daily dosing - Prevents withdrawal symptoms and craving - Blocks the euphoric effects of illicit opioids (due to cross-tolerance) - Allows stable, supervised dosing in a clinical setting ### Comparison of Opioid Agonist vs. Antagonist Approaches | Feature | Methadone | Buprenorphine | Naltrexone | |---------|-----------|---------------|----------| | **Drug Class** | Full mu-agonist | Partial mu-agonist | Mu-antagonist | | **Maintenance Role** | First-line | Alternative first-line | Not for maintenance | | **Withdrawal Prevention** | Excellent | Good | Poor (causes withdrawal) | | **Overdose Risk** | Moderate–high | Lower (ceiling effect) | None (antagonist) | | **Supervision** | Daily clinic visits | Can be office-based | Requires high motivation | | **Efficacy in Severe Dependence** | Superior | Adequate | Not suitable | **High-Yield:** Methadone requires daily supervised administration in licensed clinics in most countries, including India. Buprenorphine (partial agonist) is increasingly used as an alternative first-line agent due to lower overdose risk and better tolerability, but methadone remains the gold standard for severe, long-standing dependence. **Clinical Pearl:** Methadone maintenance reduces illicit opioid use, improves social functioning, and decreases HIV transmission risk. However, it carries a risk of QT prolongation and requires baseline and periodic ECG monitoring. **Warning:** Naltrexone is an opioid antagonist and is NOT suitable for maintenance therapy—it precipitates acute withdrawal. Naltrexone is reserved for highly motivated patients in relapse prevention after detoxification.
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