A Practical Approach to Using Adjuvant Analgesics in Older Adults

Russell K. Portenoy, MD

Disclosures

J Am Geriatr Soc. 2020;68(4):691-698. 

In This Article

Drugs Used for Neuropathic Pain

In those with chronic neuropathic pain, first-line therapies include selected multipurpose drugs, the antidepressants and the topical therapies, and gabapentinoid drugs. When neuropathic pain occurs in the context of advanced cancer, the glucocorticoids are also first-line therapies.

Gabapentinoids

The gabapentinoids gabapentin and pregabalin inhibit nociceptive neurons primarily through binding to subunits of the N-type voltage-gated calcium channel.[49] They can be useful in varied acute pain syndromes[50,51] and are the most important agents within the group of adjuvant analgesics used conventionally for chronic neuropathic pain (Table 1).[51–53]

Patients may respond to gabapentin, pregabalin, both, or neither.[54] Pregabalin may be preferred for an initial trial given pharmacokinetics that support easier and more rapid titration.[55] Serious adverse effects are uncommon, but side effects such as somnolence, dizziness, and mental clouding are common and can be very problematic in older patients. For this reason, treatment should be initiated with a low starting dose, such as pregabalin 25 to 50 mg/day or gabapentin 100 to 200 mg/day. The lowest starting doses are appropriate for patients with moderate or greater renal impairment. Dose escalation from the starting dose should be incremental and implemented at intervals long enough to allow monitoring of effects. The effective doses vary widely, and dose escalation can continue until benefit occurs or side effects begin to appear. In controlled studies, the effective pregabalin dose is usually between 150 mg/day and 600 mg/day in two divided doses,[56] and the effective gabapentin dose is usually between 900 mg/day and 3600 mg/day in two to three divided doses.[57] The effective dose in older adults may be lower than these ranges.

Other Anticonvulsants

Although evidence is limited that other anticonvulsant drugs are analgesic in neuropathic pain,[58] several drugs may be considered. Older drugs, including carbamazepine, phenytoin, and valproate, may be analgesic but have adverse-effect profiles that are less favorable than newer anticonvulsants. Among the newer drugs, oxcarbazepine was analgesic in a study of peripheral neuropathic pain[59] and both lacosamide and topiramate have limited evidence of efficacy in painful diabetic neuropathy.[60,61] No evidence is available for levetiracetam, zonisamide, and tiagabine.

The Gamma-aminobutyric Acid Agonists and Sodium Channel Blockers

The benzodiazepines are gamma-aminobutyric acid (GABA)A agonists; baclofen is a GABAB agonist used for spasticity. Anecdotal reports suggest that clonazepam may be analgesic[62] and a controlled trial suggested that baclofen is efficacious in trigeminal neuralgia.[63] Given these minimal data and the risks of adverse effects, these drugs are only rarely considered for trials when neuropathic pain has been refractory to other therapies.

Blockade of sodium channels through administration of a systemic drug, such as intravenous lidocaine or oral mexiletine, has long been recognized as having analgesic potential.[64] Intravenous lidocaine is occasionally used in a monitored setting to address severe acute pain syndromes. Given the lack of evidence and side-effect profiles that may be problematic in older adults, oral mexiletine and other similar antiarrhythmics are not favored.

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