What alternative medications can be prescribed for opioid withdrawal in a patient who refuses Suboxone (buprenorphine and naloxone)?

Alternative Medications for Opioid Withdrawal When Suboxone is Refused

If a patient refuses Suboxone for opioid withdrawal, prescribe methadone as the first-line alternative for patients at high risk of treatment dropout (injection drug users, adolescents, socially unstable patients), or prescribe clonidine/lofexidine for symptomatic management if opioid agonist therapy is completely refused. 1, 2

First-Line Alternative: Methadone

Methadone is the preferred alternative to buprenorphine for specific patient populations and has comparable effectiveness for managing opioid withdrawal. 1, 2

When to Choose Methadone Over Buprenorphine:

• Injection opioid users have higher treatment retention rates with methadone compared to buprenorphine 2
• Youth and pregnant women who inject opioids should receive methadone as first-line therapy 2
• Patients at higher risk of treatment dropout benefit from methadone's superior retention rates 2
• Methadone produces similar effectiveness to buprenorphine for reducing withdrawal severity, though symptoms may resolve slightly slower 1, 3

Methadone Dosing Approach:

• Use slow tapering of methadone to reduce severity of withdrawal symptoms 1
• Methadone requires specialized prescribing through licensed opioid treatment programs, unlike buprenorphine which can be prescribed in office-based settings 1

Critical Caution:

• Remember that patients on methadone maintenance must wait >72 hours before transitioning to buprenorphine if they later change their mind, to avoid precipitated withdrawal 1, 4

Second-Line Alternative: Alpha-2 Adrenergic Agonists

If the patient refuses all opioid agonist therapy (both buprenorphine and methadone), clonidine or lofexidine are the next best options for symptomatic management, though they are significantly less effective than opioid agonists. 1, 5

Comparative Effectiveness:

• Buprenorphine is substantially more effective than clonidine/lofexidine for managing withdrawal symptoms, with patients staying in treatment longer (SMD 0.92,95% CI 0.57 to 1.27) and more likely to complete withdrawal treatment (RR 1.64,95% CI 1.31 to 2.06) 3
• However, clonidine and lofexidine do reduce autonomic withdrawal symptoms including sweating, tachycardia, hypertension, and anxiety 5
• Patients receiving buprenorphine compared with clonidine or lofexidine had less severe signs and symptoms of withdrawal, fewer adverse effects, and stayed in treatment longer 1

Practical Use of Alpha-2 Agonists:

• These medications address sympathetic nervous system hyperactivity that occurs during opioid withdrawal 6
• Lofexidine (Lucemyra) was FDA-approved in 2018 specifically for opioid withdrawal 1
• Use the Clinical Opiate Withdrawal Scale (COWS) to assess severity and guide treatment decisions 5, 4

Monitoring Requirements:

• Monitor blood pressure closely as both clonidine and lofexidine can cause hypotension 6
• Avoid abrupt discontinuation to prevent rebound hypertension 6
• Drop-out due to adverse effects may be more likely with clonidine compared to buprenorphine 3

Symptomatic Management Approach

For mild withdrawal (COWS <8), symptomatic support alone may be sufficient without pharmacological intervention. 5

Assessment Protocol:

• Confirm time since last opioid use: >12 hours for short-acting opioids (heroin, morphine IR), >24 hours for extended-release formulations, >72 hours for methadone 1, 4
• Use COWS scoring: COWS <8 indicates mild withdrawal**, **COWS >8 indicates moderate to severe withdrawal requiring medication 1, 5

Critical Harm Reduction Measures

Regardless of which medication is chosen, always provide naloxone kits for overdose prevention, as patients in withdrawal or discontinuing treatment face significantly increased overdose risk if they return to illicit opioid use. 5, 4

Essential Preventative Services:

• Provide take-home naloxone kit and overdose prevention education 1, 5
• Offer hepatitis C and HIV screening during the withdrawal process 1, 5, 4
• Ensure access to behavioral health support and counseling, as medication alone has poor long-term outcomes 5
• Consider reproductive health counseling as appropriate 1

Common Pitfall to Avoid

The most important consideration is that opioid agonist treatment (methadone or buprenorphine) is far more effective than abstinence-based treatment or symptomatic management alone. 2 If a patient initially refuses Suboxone, continue counseling them about the substantial mortality and morbidity benefits of medication-assisted treatment, and offer methadone as an equally effective alternative rather than settling for less effective symptomatic management. 1, 2