_________________________________________________________________________ Neck Pain in Adults
Milnacipran, another SNRI, after six weeks was no different from placebo in pain reduction in chronic low back pain with
Adverse effects increase with pregabalin dose but do not appear to be age-related. In patients 65 years of age and older, titration to the lowest effective dose may help minimize adverse effects. Absence of known drug interactions with pregabalin/ gabapentin increases safety in patients requiring polypharmacy [153]. Gabapentinoid efficacy in chronic spine-related pain is inconsistent. An uncontrolled study compared pregabalin monotherapy, pregabalin add-on therapy, and non-pregabalin therapy under “real-world” primary care conditions in 1,351 patients with chronic painful cervical (13%) or lumbosacral (87%) radiculopathy [154]. Pregabalin groups received 190 mg/day (mean). At 12 weeks, pain intensity reduction ≥50% was attained by 63%, 56%, and 33% of patients in pregabalin, pregabalin add-on, and non-pregabalin groups, respectively. Differences in pain reduction were significant by week 4. Improvements in sleep disturbances, depression, anxiety, and quality of life showed large effect sizes in pregabalin groups and moderate effect sizes in the non-pregabalin group [154]. The authors noted non-pregabalin patients received NSAIDs (67%) or acetaminophen (37%) rather than tramadol (19%), gabapentin (13%), or amitriptyline (5%), indicating inappropriate treatment with NSAIDs and acetaminophen, which are ineffective in chronic pain with a neuropathic component [154]. In contrast to these uncontrolled results, a review of pregabalin/gabapentin studies in nonspecific chronic low back pain found minimal pain improvement with gabapentin compared with placebo, and pregabalin inferior to active-drug control groups (with buprenorphine, tapentadol, or celecoxib). Studies comparing pregabalin to placebo were not found [155]. In a small trial, patients with chronic cervical or lumbar radicular pain had greater pain reduction with placebo than pregabalin after three weeks [156]. Pregabalin plus tapentadol did not improve tapentadol efficacy in severe chronic low back pain with a neuropathic component and significantly increased dizziness and somnolence [157]. An uncontrolled trial of pregabalin in cervical spondylosis pain found significant pain reduction after eight weeks, but intolerable somnolence and dropout by 27 of 50 patients. The authors suggest greater sensitivity to this side effect in the Asian study population [158]. Importantly, drug users who combine heroin (and possibly some patients receiving opioid therapy) with gabapentin or pregabalin potentially increase their risk of acute overdose death by reversing opioid tolerance or through additive effects on respiratory depression [159].
a neuropathic component [151]. Antidepressant Adverse Effects
TCA side effects are intolerable for some patients, and low- dose (10 mg/day) initiation with gradual increase to 75 mg/ day is suggested [71]. TCAs should be used cautiously in elderly patients due to greater risks of postural hypotension, impaired cognition, and falls and should be avoided in patients with a history of cardiovascular disease [68; 147]. In placebo-controlled pain studies, desipramine and venlafaxine had the highest overall rates of adverse effects. Desipramine, milnacipran, venlafaxine, and duloxetine had highest dropout from side effects, suggesting greater severity and unpleasant perception. Adverse effects associated with duloxetine (e.g., nausea, constipation, dry mouth, hyperhidrosis) differed somewhat from amitriptyline (e.g., dry mouth, thirst, constipation, headache, weight gain, blurred vision, palpitations) [152]. Antiepileptic Drugs Antiepileptic drugs are diverse, but pregabalin and gabapentin are the only widely studied agents in chronic low back pain. As with antidepressants, few neck pain studies are available and chronic low back pain outcomes are used to inform decisions. Pregabalin and gabapentin are widely recommended first-line agents in neuropathic pain disorders, such as painful diabetic neuropathies and postherpetic neuralgia [70]. Analgesic, anxiolytic, and anticonvulsant effects arise from binding to alpha-2/delta-1 subunits of calcium channels, highly expressed in brainstem structures where descending pain modulatory pathways originate and a likely key analgesic target of pregabalin/gabapentin [68]. Pregabalin has greater binding affinity and greater analgesic potency in neuropathic pain than gabapentin. Pregabalin also has more rapid absorption, greater bioavailability, and a linear dose-response [68]. The dosage of pregabalin in pain treatment is 300–600 mg/ day in divided doses. Gabapentin is used at 1,200–3,600 mg/day in three divided doses. Both can be initiated at 10% the maximum dose, increased every three to four days [71]. Pregabalin 600 mg/day has greater efficacy than 300 mg/day [70]. Pregabalin/gabapentin is generally well tolerated. The adverse effects most common with pregabalin are dizziness, somnolence, dry mouth, edema, and blurred vision; with gabapentin, common adverse effects include dizziness and somnolence (>20% of patients), confusion, and peripheral edema [68].
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