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Other SE: familial obstetrical surgery malignant hyperthermia Lidocaine Local or Local infusion: local IV, SC Dose-related CV Considered most regional infiltration, and CNS toxicity widely used LA anesthesia nerve blocks, may progress to Can be combined with by infiltration epidural blocks cardiac arrest, opioids for epidural techniques (e.g., postoperative acidosis, and analgesia and IV pain, obstetrical death with IV IV use for pain regional pain), arthroscopy administration normally reserved for anesthesia CNS SE: pain refractory to other IV infusion: (rarely lightheadedness, treatments due to risk used) for some dizziness, of toxicity and unclear nociceptive and drowsiness, efficacy neuropathic pain, tinnitus, tremors, Topical lidocaine (see burn pain convulsions, EMLA®, Lidocaine unconsciousness patch) is not associated CV SE: bradycardia, with same side effects hypotension, CV collapse IV lidocaine contraindicated in patients with hypersensitivity to amide-type LAs, Adams-Stoke syndrome, severe heart block Sources: References 19, 20, 50, and 104-142. aThis is a representative, not comprehensive, list. bMost uses are off label. AV: atrioventricular; CNCP: chronic noncancer pain; CNS: central nervous system; CV: cardiovascular; ECG: electrocardiogram; EMLA®: Eutectic Mixture of Local Anesthetics (lidocaine and prilocaine); ER: extended release; FDA: Food and Drug Administration; HA: headache; HIV: human immunodeficiency virus; IN: intranasal; IV: intravenous; LA: local anesthetics; LBP: lower back pain; MI: myocardial infarction; MOAI: monoamine oxidase inhibitor; MS: musculoskeletal; OA: osteoarthritis; PDN: peripheral diabetic neuropathy; PHN: postherpetic neuralgia; PSP: postsympathectomy pain; QTc: QT interval corrected for heart rate on ECG; RSD: reflex sympathetic dystrophy; SC: subcutaneous; SE: side effects; TCAs: tricyclic antidepressants; TN: trigeminal neuralgia. but clinical trial evidence of its analgesic efficacy is limited and conflicting.c,108-109 Clinical trial data support the use of carbamazepine in the treatment of trigeminal neuralgia, diabetic peripheral neuropathy, and postherpetic neuralgia,112 but serious, albeit rare, side effects limit its use.101 Recent data suggest that newer AEDs such as gabapentin are better alternatives to older AEDs.101,110,112 Placebo-controlled clinical trials have demonstrated that gabapentin provides effective analgesia comparable to TCAs for diabetic peripheral neuropathy146-147 and postherpetic neuralgia;114 it also has a more favorable side effect profile.110,112 Data from a large study and a recent placebo-controlled trial also suggest that gabapentin effectively reduces the likelihood of migraine headaches.115-116 Uncontrolled studies suggest that gabapentin also may be useful in the management of trigeminal neuralgia, central pain, phantom limb pain, and neuropathy associated with human immunodeficiency virus (HIV) infection.120,148-150 Thus, many pain experts consider gabapentin a first-line treatment for neuropathic pain.105,109,112,117-118 iii. Side effects Side effects of AEDs vary (Table 25). Common side effects of AEDs as a class include sedation, mental clouding, dizziness, nausea, or unsteadiness.107 Initiating treatment at low doses and slowly titrating upward to optimal efficacy or toxicity diminishes the risk of these effects. Table 26 summarizes other ways to prevent and manage side effects. Less common but more serious adverse effects of some of the older AEDs include hematologic abnormalities, liver dysfunction, hypersensitivity reactions, and rash (Table 25). Thus, use of some of these agents requires close monitoring of drug levels, hematologic parameters, and liver function.105 Unlike these older AEDs, gabapentin offers easy monitoring and relatively low toxicity (i.e., minimal drug-drug interactions and side effects).101,110,112,119-120 d. Antidepressants i. Mechanism of action and effects Antidepressants exhibit analgesic properties in animal models of nociceptive, inflammatory, and neuropathic pain, and some relieve chronic and neuropathic pain in humans.151 These analgesic effects may reflect the ability of some antidepressants to block the reuptake of serotonin and norepinephrine in the CNS, thus increasing the activity of endogenous pain-modulating pathways.152-154 Their analgesic actions do not depend on antidepressant activity,155 and antidepressants are equally effective in patients with and without depression.19 While analgesia may occur at lower doses and sooner than antidepressant activity, maximum efficacy may require high antidepressant doses and trial duration. ii. Indications and uses TCAs (e.g., amitriptyline, nortriptyline, imipramine) are adjuvant analgesics used to treat a variety of types of chronic (e.g., migraine, other headaches, low back pain, cancer pain, fibromyalgia) and neuropathic (e.g., painful diabetic neuropathy, postherpetic neuralgia, central pain, cancer-related) pain (Table 25).107,122 All of these uses are “off-label.” Although often considered most effective for continuous dysethesias (i.e., burning pain or hypersensitivity), TCAs also may relieve lancinating neuropathic pain.122,156-157 Currently, TCAs are the only antidepressants with clearly demonstrated analgesic efficacy. Placebo-controlled clinical trial data suggest that TCAs provide effective158-159 and
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