What are the recommended guidelines for prescribing long‑term opioid analgesics to adult patients with chronic moderate‑to‑severe pain?

Guidelines for Long-Term Opioid Analgesic Use

Opioids should only be prescribed for chronic pain after documented failure of nonopioid therapies (acetaminophen, NSAIDs, gabapentin, SNRIs), and only when expected benefits for pain relief and function outweigh serious risks including respiratory depression, addiction, and death. 1

Pre-Initiation Requirements

Before starting any opioid therapy, you must complete the following:

• Document comprehensive history and physical examination focusing on pain characteristics, prior treatments tried and failed, substance use history (including alcohol), psychiatric conditions (depression, anxiety, suicidal ideation), and family history of substance abuse 1, 2
• Check state Prescription Drug Monitoring Program (PDMP) to identify doctor shopping, concurrent prescriptions, or high-risk combinations 1
• Obtain baseline urine drug screen to detect undisclosed substance use 1, 2
• Screen for depression using two questions: "During the past 2 weeks have you been bothered by feeling down, depressed, or hopeless?" and "During the past 2 weeks have you been bothered by little interest or pleasure in doing things?" 3
• Assess overdose risk factors including sleep apnea, concurrent benzodiazepine use, alcohol use, and respiratory conditions 1

Treatment Hierarchy: What Must Fail First

First-line therapy (must try before opioids):

• Acetaminophen up to 4g/day (lower in liver disease) 3, 4
• NSAIDs (ibuprofen, naproxen) with gastroprotection if needed 3, 5
• For neuropathic pain: Gabapentin titrated to 2400mg/day in divided doses 3
• Physical therapy, cognitive behavioral therapy, and exercise programs 1, 3

Second-line therapy (try before opioids):

• SNRIs (duloxetine or venlafaxine) for neuropathic components 3
• Pregabalin as alternative gabapentinoid 3
• Tramadol 37.5-400mg/day for up to 3 months (lower addiction risk than traditional opioids) 1, 3, 4

Opioid Initiation Protocol (Only After Above Failures)

Starting dose and formulation:

• Begin with 15-30mg oral morphine equivalent every 4 hours as needed (short-acting formulation only) 6
• Never start with extended-release/long-acting (ER/LA) formulations 1
• Never prescribe ≥50 morphine milligram equivalents (MME)/day initially 1
• Use the lowest possible dose of short-acting opioids only 1

Dose categories to guide prescribing:

• Low dose: Up to 40mg MME/day 2
• Moderate dose: 41-90mg MME/day 2
• High dose: >91mg MME/day (requires extreme caution and specialist consultation) 2

Mandatory Patient Agreement and Informed Consent

Execute a written opioid patient-provider agreement covering:

• Realistic expectations: No good evidence exists that long-term opioids improve pain and function 1
• Serious risks: Death from respiratory depression, lifelong opioid use disorder, cognitive impairment, constipation, nausea, drowsiness 1
• Increased risk when combined with benzodiazepines, alcohol, or other CNS depressants 1
• Single prescriber and single pharmacy requirements 2
• Agreement to random urine drug testing and pill counts 2

Ongoing Monitoring Requirements

At every visit (minimum every 1-4 weeks initially, then every 3 months):

• Reassess pain intensity and functional improvement using standardized scales (e.g., PEG scale) 1
• Check PDMP for concurrent prescriptions 1
• Calculate total daily MME and ensure ≤90 MME/day 1
• Observe for signs of overdose: sedation, respiratory depression, pinpoint pupils 1
• Screen for opioid use disorder symptoms 1
• Perform random urine drug testing to confirm prescribed opioid presence and detect undisclosed substances 1, 2

Critical threshold requiring action:

• If dose approaches or exceeds 50 MME/day, carefully reassess benefits versus risks 1
• At 90 MME/day or above, strongly consider dose reduction or discontinuation 1

Absolute Contraindications to Opioid Therapy

Do not prescribe opioids if any of the following exist:

• Concurrent benzodiazepine use (avoid whenever possible) 1
• Active alcohol or substance abuse 2
• Respiratory instability or severe sleep apnea 2
• Acute psychiatric instability or uncontrolled suicide risk 2
• Active diversion of controlled substances 2

When to Transition to Long-Acting Formulations

Only after stable pain control achieved with short-acting opioids:

• Convert total 24-hour short-acting dose to equivalent extended-release formulation 1
• Provide rescue doses of short-acting opioid equal to 10-20% of total daily dose for breakthrough pain, available every hour as needed 1
• Caution: Conversion can lead to excessive sedation at peak levels; close observation mandatory 6

Mandatory Constipation Prophylaxis

• Start stimulant laxative (senna, bisacodyl) simultaneously with opioid initiation 1
• Add stool softener (docusate) as indicated 1
• Anticipate and treat prophylactically—do not wait for constipation to develop 1

Decision Points for Continuation, Tapering, or Discontinuation

Continue opioids only if:

• Documented clinically meaningful improvement in pain (≥30% reduction) AND functional status 1
• No evidence of misuse, diversion, or opioid use disorder 1
• Benefits clearly outweigh harms at each reassessment 1

Taper or discontinue if:

• No meaningful improvement in pain or function after 3 months 1
• Evidence of misuse, doctor shopping, or diversion 1
• Development of opioid use disorder 1
• Intolerable side effects 1
• Patient requests discontinuation 1

Tapering Protocol When Discontinuing

Taper slowly to avoid withdrawal:

• Reduce by no more than 10-25% of total daily dose every 2-4 weeks 6
• Patients on opioids for shorter periods may tolerate faster taper 6
• Monitor for withdrawal symptoms: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, mydriasis, irritability, anxiety, insomnia, nausea, diarrhea 6
• If withdrawal symptoms emerge, pause taper or increase dose slightly, then resume slower taper 6
• Ensure multimodal pain management and mental health support are in place before initiating taper 6

Special Considerations for Methadone

Reserve methadone for late-stage therapy after other opioid failures:

• Prescribe only if you have specific training in methadone risks and pharmacology 2
• Obtain baseline ECG before initiation, repeat at 30 days, then yearly to monitor QTc prolongation 2

Common Pitfalls to Avoid

• Never prescribe ER/LA opioids as initial therapy—this violates CDC guidelines and increases overdose risk 1
• Never combine opioids with benzodiazepines—dramatically increases respiratory depression and death risk 1
• Never exceed 90 MME/day without compelling justification—mortality risk increases substantially above this threshold 1
• Never continue opioids without documented functional improvement—pain reduction alone is insufficient justification 1
• Never prescribe without checking PDMP—failure to identify concurrent prescriptions enables overdose 1