The Clinical Guide to Supportive and Palliative Care for HIV/AIDS

A Clinical Guide to Supportive and Palliative Care for HIV/AIDS • Chapter 4: PainAntidepressantsThe current literature supports the use of antidepressants as adjuvant analgesic agents in the management26of a widepicasvariety of chronic pain syndromes, including cancer pain, postherpetic neuralgia,diabetic neuropathy, fibromyalgia, headache and low back pain. 79, 80, 81, 82, 83, 84 The antidepressantsare analgesic through a number of mechanisms that include antidepressant activity, 80 potentiationor enhancement of opioid analgesia, 85, 86, 87 and direct analgesic effects. 88The leading hypothesis suggests that both serotonergic and noradrenergic properties of the antidepressantsare important, and that variations among individuals in pain (as to the status of their ownneurotransmitter systems) are an important variable. 54 Other possible mechanisms of antidepressantanalgesic activity that have been proposed include adrenergic and serotonin receptor effects,adenosinergic effects, anti-histaminic effects, and direct neuronal effects, such as inhibition ofparoxysmal neuronal discharge and decreasing sensitivity of adrenergic receptors on injured nerve86, 89, 90, 91sprouts.There is substantial evidence that the tricyclic antidepressants in particular are analgesic anduseful in the management of chronic neuropathic and non-neuropathic pain syndromes. Amitriptylineis the tricyclic antidepressant most studied and has been proven effective as an analgesic ina large number of clinical trials addressing a wide variety of chronic pain syndromes, includingneuropathy, cancer pain, fibromyalgia and others. 54, 80, 81, 92, 93, 94 Other tricyclics that have beenshown to have efficacy as analgesics include imipramine, desipramine, nortriptyline,clomipramine, 100 55, 95, 96, 97, 98, 99, 101and doxepin.The heterocyclic and non-cyclic antidepressant drugs may be useful as adjuvant analgesics forchronic pain syndromes. 54, 81, 88, 96, 97, 102, 103, 104, 105, 106, 107 These drugs include trazodone, mianserin,maprotiline and the newer serotonin-specific reuptake inhibitors (SSRIs), fluoxetine and paroxetine.Fluoxetine, a potent antidepressant with specific serotonin reuptake inhibition activity, has beenshown to have analgesic properties in experimental animal pain models but failed to show analgesiceffects in a clinical trial for neuropathy. 97, 106, 107 Several case reports suggest fluoxetine may be a108, 109useful adjuvant analgesic in the management of headache and fibrositis.Paroxetine, a newer SSRI, is the first antidepressant of this class shown to be a highly effectiveanalgesic in a controlled trial for the treatment of diabetic neuropathy. 96 Newer antidepressantssuch as sertraline, venlafaxine, and nefazodone may also eventually prove to be clinically useful asadjuvant analgesics. For instance, nefazodone has been demonstrated to potentiate opioid analgesicsin an animal model. 110Given the diversity of clinical syndromes in which the antidepressants have been demonstrated tobe analgesic, trials of these drugs can be justified in the treatment of virtually every type of chronicpain. 111 The established benefit of several of the antidepressants in patients with neuropathic pains,however, suggests these drugs may be particularly useful with cancer and AIDS patients, where anunderlying neuropathic component to the pain(s) often exists. 96, 97, 111 While studies of the analgesicefficacy of these drugs in HIV-related painful neuropathies have not yet been conducted, the drugsare widely applied clinically using the model of diabetic and post-herpetic neuropathies.IVU.S. Department of Health and Human Services • Health Resources and Services Administration • HIV/AIDS Bureau 111