Tricyclic Antidepressants
51. What types of pain are most responsive to antidepressants? Is there any advantage of using one antidepressant over another for pain management in patients such as R.L.?
The analgesic properties of TCAs are independent of their antidepressant properties. Depression, however, often accompanies chronic pain, which in turn, often exacerbates a patient's response to pain and inability to cope with pain-induced lifestyle changes.163,164 Thus, the antidepressant may interrupt this cycle of events. TCAs produce analgesia directly through modulation of the descending inhibitory nerve pathway by either altering serotonin or norepinephrine neurotransmission. They are also believed to reduce pain through local anesthetic (sodium-channel blocking) effects. Another secondary benefit of some TCAs is their sedative effect, which can help the patient sleep and reduce feelings of anxiety.
Antidepressants have been most widely studied in patients with diabetic neuropathy and postherpetic neuralgia.165,166 They also have some value in deafferentation pain (central pain resulting from loss of spinal afferent nerve pathway), phantom limb pain, human immunodeficiency virus (HIV) neuropathy,167 postsurgical pain,168,169 fibromyalgia, and chronic pain associated with depression. They also have limited usefulness in the management of lower back pain, radiation neuropathy, and direct malignant nerve infiltration.
Clinical data for the management of pain is most extensive for amitriptyline, but other TCAs also have been used for this purpose.160,170 Data on the use of SSRIs, such as fluoxetine, paroxetine, and sertraline, are limited.171 The major disadvantage associated with the use of TCAs is their side-effect profile, which includes sedation, anticholinergic effects, and cardiotoxicity (quinidinelike widening of QRS on electrocardiogram [ECG]). Sedation and anticholinergic effects are less severe with secondary amine TCAs (desipramine, nortriptyline) than with tertiary amine TCAs, such as amitriptyline and doxepin. Weight gain can be a limiting factor as well.172,173 In patients such as R.L., who have no histories of cardiac problems, a TCA can be helpful in pain management. Whether TCAs should be used to treat pain in the elderly population remains controversial because these agents also can produce cognitive impairment and hypotension.174
52. L.K., a 46-year-old woman with diabetes mellitus, is admitted to the hospital with pain that involves both hands and feet and which is associated with symptoms of pain, burning sensation, numbness, and tingling. Physical examination reveals only that pinprick sensation in the hands and feet is lessened.
Another class of antidepressants, the serotonin-norepinephrine reuptake inhibitors, duloxetine hydrochloride and venlafaxine provide an alternative for patients whose use of a TCA may be limited because of side effects. These drugs act by providing dual reuptake inhibition of both serotonin and norepinerhrine transporters with weak affinity for the dopamine transporter. The most frequently observed side effects with duloxetine are nausea, vomiting, constipation, somnolence, dry mouth, increased sweating, loss of appetite, and weakness. The immediate-release version of venlafaxine is associated with more CNS and somatic side effects, but the extended-release version of this medication is more tolerable with the main side effect being gastrointestinal disturbances. The optimal dose of duloxetine is 60 mg/day with 150 to 225 mg/day being an effective dose for venlafaxine.175,176
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