What is the next step for a patient experiencing withdrawal symptoms while on Suboxone (buprenorphine/naloxone) 8mg twice daily (BID)?

Increase Buprenorphine Dose for Persistent Withdrawal Symptoms

Yes, increase the Suboxone dose—the patient is experiencing breakthrough withdrawal symptoms on 16 mg daily (8 mg BID), indicating inadequate mu-receptor occupancy that requires dose escalation to achieve therapeutic effect. 1

Immediate Assessment and Action

Before increasing the dose, verify the following critical factors:

• Confirm true withdrawal symptoms using the Clinical Opiate Withdrawal Scale (COWS) to objectively document withdrawal severity—look for specific signs including pupil dilation, sweating, restlessness, GI upset, muscle aches, and elevated pulse rate 1
• Rule out precipitated withdrawal by confirming adequate time has elapsed since last full opioid agonist use (>12 hours for short-acting opioids, >24 hours for extended-release formulations, >72 hours for methadone) 1
• Assess for drug interactions that may reduce buprenorphine efficacy, particularly CYP3A4 inducers (rifampin, carbamazepine, phenytoin) which decrease buprenorphine plasma concentrations and can cause withdrawal symptoms 2

Recommended Dose Escalation Strategy

Increase to 24 mg daily (12 mg BID or 24 mg once daily) as the standard maintenance dose for most patients is 16 mg daily, with a therapeutic range of 4-24 mg 1. The current 16 mg dose is at the lower end of the maintenance range and can be safely increased.

Dosing Algorithm:

• Day 1: Increase to 20 mg total daily dose (10 mg BID), reassess after 2-4 hours for symptom improvement 1
• Day 2: If withdrawal persists, increase to 24 mg daily (12 mg BID or single daily dose) 1
• Ongoing: Monitor for 3-5 days at the new dose before further adjustments, as buprenorphine has a long half-life (24-42 hours) and requires time to reach steady state 1

Critical Pharmacology Considerations

Buprenorphine occupies approximately 95% of mu-opioid receptors at doses of 16 mg and above, creating a ceiling effect for both therapeutic benefit and respiratory depression 3. However, this does not mean higher doses are ineffective—some patients require doses up to 24 mg for adequate withdrawal suppression and craving control 1.

The partial agonist properties of buprenorphine mean that:

• It provides sufficient agonist activity to eliminate withdrawal symptoms while blocking effects of other opioids 1
• The ceiling effect on respiratory depression makes dose escalation safer than with full agonists 1
• Higher doses may be needed for patients with high opioid tolerance or those using potent synthetic opioids like fentanyl 1

Alternative Explanations to Investigate

Before attributing symptoms solely to inadequate dosing, evaluate:

• Continued illicit opioid use: Order urine drug screen to document any ongoing use of full agonist opioids, which would indicate inadequate therapeutic effect 3
• Persistent cravings: Ask specifically about opioid cravings, as this is a primary indicator for dose escalation even without objective withdrawal signs 3
• Early return of symptoms: Determine if withdrawal symptoms emerge before the next scheduled dose (end-of-dose failure), which may require splitting the daily dose into more frequent administrations rather than increasing total dose 3
• Comorbid psychiatric conditions: Anxiety, depression, or protracted withdrawal symptoms may mimic acute withdrawal and require separate treatment rather than dose escalation 3

Monitoring and Follow-up

After dose increase:

• Reassess COWS score at 30-60 minutes and 2-4 hours post-dose to document objective improvement 1
• Monitor for oversedation in the first 24-48 hours, though this is unlikely given buprenorphine's ceiling effect on respiratory depression 1
• Schedule follow-up within 3-7 days to assess response and determine if further adjustment is needed 1
• Provide take-home naloxone and overdose prevention education, as any change in opioid dosing alters tolerance 1

Critical Safety Warnings

• Do not abruptly discontinue buprenorphine if dose escalation is ineffective—discontinuation precipitates withdrawal and dramatically increases relapse risk to more dangerous opioids 1
• Screen for QT-prolonging medications as concomitant use with buprenorphine is contraindicated 4, 3
• Monitor for serotonin syndrome if patient is taking SSRIs, SNRIs, or other serotonergic medications, as combination with buprenorphine increases this risk 2
• Avoid benzodiazepines when possible due to additive CNS depression, or use with extreme caution and careful monitoring 2

When NOT to Increase Dose

Do not increase buprenorphine dose if:

• Patient is using illicit opioids on top of buprenorphine (address adherence and psychosocial support first) 3
• Symptoms are primarily psychiatric (anxiety, insomnia) rather than true opioid withdrawal 3
• Patient is experiencing precipitated withdrawal from premature buprenorphine administration—in this case, give MORE buprenorphine rapidly to outcompete the precipitated withdrawal, not less 1, 5

Long-term Perspective

There is no maximum recommended duration of buprenorphine maintenance treatment—patients may require treatment indefinitely, and the goal is not tapering but rather stable maintenance at the lowest effective dose that prevents withdrawal, eliminates cravings, and allows functional recovery 1. The typical maintenance dose of 16 mg daily is effective for most patients, but 24 mg is well within the therapeutic range and appropriate for those with breakthrough symptoms 1.