Pharmacy & Therapeutics - March 2008 - (Page 173) CONTINUING EDUCATION CREDIT Choosing a First-Line Agent Because of their proven clinical efficacy in DPN, a first-line agent should be used to initiate treatment. When choosing among agents, prescribers should consider cost; comorbid conditions, including depression (Table 11); and the patient’s overall clinical picture.6,57–59 Because of the concern for potential drug interactions and contraindications, a review of the patient’s current medication profile is warranted. If a TCA is chosen, agents with the most consistently proven efficacy should be considered. From studies reviewed, it is reasonable to try imipramine, desipramine, and amitriptyline.6 Desipramine is preferred in the elderly, because it is associated with fewer anticholinergic effects. If an opioid is chosen as a first-line therapy, health care providers should exercise caution in patients with an active abuse disorder, a history of substance abuse, or those whose risk of opioid abuse is unclear. Health care providers and patients should agree upon a structured treatment plan, and methods of assessing adherence to the regimen should be developed; for example, pill counts, urine toxicology screenings, and unscheduled office visits should be considered.60 Considerations for Older Adults The prevalence of pain in patients older than 60 years of age is twice as high as in younger patients.61 Treatment may be complicated by the presence of dementia, renal and liver impairment, and increased sensitivity to adverse effects. Although these barriers exist, careful treatment selection allows elderly patients to be optimally managed. TCAs cause a number of side effects to which older adults may already be prone. These include heart block, orthostatic hypotension, dry mouth, urinary retention, and constipation. Table 11 Factors to Consider in Choosing First-Tier Agents Recommended Medical comorbidities Glaucoma Orthostatic phenomena Cardiac or electrocardiographic abnormality Hypertension Renal insufficiency Hepatic insufficiency Falls or balance issues Psychiatric comorbidities Depression§ Anxiety Suicidal ideation Somatic problems Sleep Erectile dysfunction Other factors Cost Drug interactions Weight gain Edema TCAs, generic oxycodone CR Oxycodone CR, pregabalin Duloxetine, oxycodone CR Any other first-tier agent Duloxetine, pregabalin Duloxetine, TCAs// TCAs, pregabalin Pregabalin Any first-tier agent Second-tier agent venlafaxine All first-tier agents Duloxetine, TCAs Duloxetine, pregabalin, TCAs Duloxetine, pregabalin Oxycodone CR, pregabalin Oxycodone CR TCAs, oxycodone CR Any other first-tier agent* Any other first-tier agent Any other first-tier agent Any other first-tier agent Any first-tier agent†‡ Any others Any others Duloxetine TCAs, pregabalin TCAs TCAs TCAs TCAs Avoid * Duloxetine is contraindicated only for patients with uncontrolled narrow-angle glaucoma and may be appropriate for other glaucoma patients. † Dosage adjustment of oxycodone CR and pregabalin is recommended for patients with a creatinine clearance below 60 mL/minute. ‡ Duloxetine is not recommended for patients with a creatinine clearance below 30 mL/minute. § Before treatment with an antidepressant is initiated, patients with depressive symptoms should be adequately screened to determine whether they are at risk for bipolar disorder. // The prescribing information should be consulted for individual agents concerning specific drug–drug interactions and contraindications. CR = controlled-release; TCAs = tricyclic antidepressants. Adapted with permission from Argoff CE, Backonja MM, Belgrade MJ, et al. Mayo Clinic Proceedings 2006;81(4 Suppl):S12–S25.6 Vol. 33 No. 3 • March 2008 • P&T® 173
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