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Summary

Acetaminophen: pearls — acetaminophen labeling recommends a dose of ≤3 g/day, but patients without liver disease appear to tolerate ≤4 g/day; patients aged >65 yr can be reassured that this dose is safe for brief periods (liver function tests may be performed); patients should be encouraged to discuss use of over-the-counter (OTC) medications with their health care providers; data show patients have a false perception that prescribed opioid medications are always more effective but pose a greater risk than OTC medications, which is not universally true; pitfalls — most are related to combinations of acetaminophen with other drugs (eg, hydrocodone [eg, Lorcet, Norco, Vicodin], oxycodone [eg, Endocet, Percocet, Primlev), ibuprofen [Advil Dual Action]); patients should be counseled about potential for toxicity; acetaminophen overdose is common because of its ubiquitous use and the difficulty of calculating doses when combination drugs are being used (separate prescriptions are recommended); concomitant use of alcohol (which can be assessed with brief screening tools) affects liver metabolism and increases risk for toxicity; in rare cases, acetaminophen may cause severe skin reactions associated with Stevens-Johnson syndrome or toxic epidermal necrolysis

Nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (cox)-1 and 2 inhibitors prescribed for acute and chronic pain; gastrointestinal (GI) adverse effects (eg, ulcers, dyspepsia) appear in a dose-dependent manner; industry-supported studies suggested a lower incidence of GI effects with cox-2 inhibitors, but recent data find no difference between the 2 types; cardiovascular adverse effects also occur and are dose dependent; NSAIDs should not be prescribed after cardiac surgery; also associated with increased thrombotic risk in patients taking anticoagulant agents; should be used intermittently, at the lowest effective doses (eg, a 2-wk course after surgery); longer-term use increases risk for adverse events; ketoprofen inhibits cox-1; the most common nonselective cox inhibitors are OTC drugs, eg, ibuprofen, naproxen; cox-2 inhibitors include diclofenac (older) and celecoxib (newer); the safety profile is better established for cox-1 inhibitors; cox-2 agents can be considered for patients who do not receive adequate pain relief with cox-1 inhibitors; acetaminophen plus NSAID — provides greater pain relief than either medication taken alone; per a review by Moore and Hersh (2013), the number needed to treat was lower than that for oxycodone 10 mg; effective for acute pain; higher doses can be taken less often (eg, both drugs every 6 hr); another option is to prescribe lower doses, with alternation between the NSAID and acetaminophen and dosing at more frequent intervals

Serotonin norepinephrine reuptake inhibitors (SSRIs): duloxetine — prescribed for chronic pain (eg, diabetic neuropathy, fibromyalgia, musculoskeletal conditions [eg, nonspecific low back pain]); may be started at 30 mg for 5 to 7 days and doubled to 60 mg if no response is seen; higher doses (90-120 mg) are prescribed for anxiety and other mental health conditions but do not improve relief of chronic pain; venlafaxine — chronic pain is not an Food and Drug Administration (FDA)-approved indication, but this SSRI may be effective for patients with anxiety who do not respond to duloxetine; SSRIs should be tapered slowly to avoid adverse effects, eg, mood changes

Black box warning: cites risk for suicide and mood effects; most antidepressants cause mood changes during the first 2 to 4 wk, even with the lower doses used for chronic pain

Gabapentinoids: considered controlled substances in some states; gabapentin — approved by the FDA for relief of pain due to postherpetic neuralgia; doses may start as low as 100 mg/day and are gradually increased; patients often start at 300 mg/day, which may be increased from daily dosing to 3 times/day, typically to a maximum of 1800 mg/day; dosing decisions should consider renal function; the most commonly reported adverse effects are dizziness and somnolence; temporary impairment of driving ability is possible; peripheral edema occurs in 2% to 3% of patients; pregabalin — approved for fibromyalgia, neuropathic pain, diabetic peripheral neuropathy, and postherpetic neuralgia; most insurers cover stepwise therapy (ie, starting with gabapentin, then switching to pregabalin if response is inadequate); doses are titrated in 25- to 75-mg increments, typically to 300 mg/day; adverse effects and renal precautions are similar to those of gabapentin; pregabalin is more expensive than gabapentin

Cannabinoids: reportedly beneficial for pain in some patients; the FDA has not approved cannabinoids for acute or chronic pain; dronabinol (Marinol) is an oral solution used to improve appetite; oral sprays containing tetrahydrocannabinol (THC) and cannabidiol (CBD), eg, nabiximols (Sativex) are currently being investigated in clinical trials (available in the United Kingdom and approved for chronic pain by the European Medicines Agency); CBD was recently approved only for a specific type of pediatric seizure

Cannabis use: in national surveys, reported by nearly 20% of Americans >12 yr of age; 5% report cannabis use disorder

Cannabis and prescribed opioids: patients with chronic pain typically report reduced use of opioids associated with cannabis use; however, this assertion is not robustly supported by (sparse) longitudinal studies (ie, the magnitude of the dose reduction may be smaller than that reported by patients); studies have not consistently found a link between legalization of cannabis and a reduction in opiate-related deaths across the United States; cannabis use increases the risk for opioid misuse