CS263451 April 27, 2016

NONOPIOID TREATMENTS 

FOR CHRONIC PAIN

PRINCIPLES OF CHRONIC PAIN TREATMENT

Patients with pain should receive treatment that provides the greatest benefit. Opioids are not the first-line therapy for 

chronic pain outside of active cancer treatment, palliative care, and end-of-life care. Evidence suggests that nonopioid 

treatments, including nonopioid medications and nonpharmacological therapies can provide relief to those suffering 

from chronic pain, and are safer. Effective approaches to chronic pain should: 

Use nonopioid therapies to the extent possible 

Identify and address co-existing mental health

conditions (e.g., depression, anxiety, PTSD) 

Focus on functional goals and improvement, engaging

patients actively in their pain management 

Use disease-specific treatments when available (e.g., 

triptans for migraines, gabapentin/pregabalin/duloxetine 

for neuropathic pain) 

Use first-line medication options preferentially 

Consider interventional therapies (e.g., 

corticosteroid injections) in patients who fail 

standard non-invasive therapies 

Use multimodal approaches, including

interdisciplinary rehabilitation for patients who have

failed standard treatments, have severe functional

deficits, or psychosocial risk factors

NONOPIOID MEDICATIONS

MEDICATION MAGNITUDE OF

BENEFITS HARMS COMMENTS

Acetaminophen Small Hepatotoxic, particularly at 

higher doses First-line analgesic, probably less effective than NSAIDs

NSAIDs Small-moderate Cardiac, GI, renal First-line analgesic, COX-2 selective NSAIDs less GI toxicity

Gabapentin/pregabalin Small-moderate Sedation, dizziness, ataxia First-line agent for neuropathic pain; pregabalin approved for fibromyalgia

Tricyclic antidepressants and 

serotonin/norephinephrine 

reuptake inhibitors

Small-moderate

TCAs have anticholinergic 

and cardiac toxicities; 

SNRIs safer and better 

tolerated

First-line for neuropathic pain; TCAs and SNRIs for fibromyalgia, TCAs for 

headaches

Topical agents (lidocaine, 

capsaicin, NSAIDs) Small-moderate

Capsaicin initial flare/

burning, irritation of 

mucus membranes

Consider as alternative first-line, thought to be safer than systemic 

medications. Lidocaine for neuropathic pain, topical NSAIDs for localized 

osteoarthritis, topical capsaicin for musculoskeletal and neuropathic pain

LEARN MORE | www.cdc.gov/drugoverdose/prescribing/guideline.html
RECOMMENDED TREATMENTS FOR COMMON CHRONIC 

PAIN CONDITIONS 

Low back pain

Self-care and education in all patients; advise 

patients to remain active and limit bedrest

Nonpharmacological treatments: Exercise, cognitive 

behavioral therapy, interdisciplinary rehabilitation 

Medications 

• First-line: acetaminophen, non-steroidal anti inflammatory 

drugs (NSAIDs) 

• Second-line: Serotonin and norepinephrine reuptake inhibitors 

(SNRIs)/tricyclic antidepressants (TCAs)

Migraine

Preventive treatments 

• Beta-blockers 

• TCAs 

• Antiseizure medications 

• Calcium channel blockers 

• Non-pharmacological treatments (Cognitive behavioral 

therapy, relaxation, biofeedback, exercise therapy) 

• Avoid migraine triggers 

Acute treatments

• Aspirin, acetaminophen, NSAIDs (may be combined

with caffeine) 

• Antinausea medication 

• Triptans-migraine-specific 

Neuropathic pain

Medications: TCAs, SNRIs, gabapentin/pregabalin, 

topical lidocaine 

Osteoarthritis

Nonpharmacological treatments: Exercise, weight 

loss, patient education 

Medications 

• First-line: Acetamionphen, oral NSAIDs, topical NSAIDs 

• Second-line: Intra-articular hyaluronic acid, capsaicin

(limited number of intra-articular glucocorticoid injections

if acetaminophen and NSAIDs insufficient)

Fibromyalgia

Patient education: Address diagnosis, treatment, 

and the patient’s role in treatment

Nonpharmacological treatments: Low-impact aerobic 

exercise (e.g., brisk walking, swimming, water 

aerobics, or bicycling), cognitive behavioral therapy, 

biofeedback, interdisciplinary rehabilitation 

Medications 

• FDA-approved: Pregabalin, duloxetine, milnacipran 

• Other options: TCAs, gabapentin

LEARN MORE | www.cdc.gov/drugoverdose/prescribing/guideline.html