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Antidepressants
Tricyclic antidepressants are useful as adjutant analgesics in the pharmacologic management of cancer pain, especially neuropathic pain. These drugs potentiate the analgesic effects of opioids in animal models of pain 57; 432 and have innate analgesic properties257; 303. They are effective through mechanisms that include: (1) mood elevation,167 (2) potentiation or enhancement of opioid analgesia,479 and (3) direct analgesic effects.305
The most widely reported experience has been with amitriptyline; therefore, it should be viewed as the tricyclic agent of choice, even though it produces anti-cholinergic side effects such as dry mouth, constipation, and urinary retention in many patients. Analgesic treatment failure may be due to low levels in serum.167 305 Doses of amitriptyline of up to 150 mg daily or higher may be required to obtain therapeutic effects concentrations.269; 493 In the treatment of diabetic neuropathy pain, the therapeutic analgesic effects of amitriptyline appear to be correlated with concentrations in serum above 100 ng/mL. However, a corresponding relationship between amitriptyline concentrations in serum and analgesia has not been reported in cancer pain.
The onset of analgesic effects occurs within 1 to 2 weeks after the start of therapy and peaks at 4 to 6 weeks.167; 305; 371 Treatnent should be initiated with a small dose of amitriptyline (10 to 25 mg at bedtime), especially in debilitated patients, and increased slowly by 10 to 25 mg every 2 to 4 days toward 150 mg. This approach takes advantage of the sedative effects of the drug and minimizes the risk of falling (especially in elderly patients) because of orthostatic hypotension. Amitriptyline is also useful when sleep disturbance complicates the presence of pain and depression, because its initial use is commonly associated with sedation.
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