Health Articles

Antihistamines (eg, hydroxyzine, diphenhydramine, and orphena-drine) may have analgesic activity, although supporting data are limited. One of these agents may be selected for patients with pain and an associated indication for antihistamine therapy; eg, those with pain from a malignancy and anxiety or nausea may be given a trial of hydroxyzine 25 to 50 mg orally qid. The anticholinergic and sedative effects of these drugs in the elderly patient should always be considered.

Corticosteroids have been used in reflex sympathetic dystrophy (prednisone 60 mg daily in divided doses, tapered over 2 wk), in acute herpetic neuralgia in the immunocompetent host (see POSTHERPETIC NEURALGIA, below), and in malignant pain due to tumor invasion of bone or nerve trunks (empirically chosen as methylprednisolone, prednisone, or dexamethasone at a dose equivalent to 80 mg prednisone daily). The risks of short-term therapy with these agents are generally low. Concurrent diseases such as diabetes or heart failure may change these considerations.

These drugs may be used for analgesia. Nifedipine has been used in refractory reflex sympathetic dystrophy, and both nifedipine (usually 10 mg orally tid) and verapamil (80 mg orally tid or qid) may have efficacy in migraine prophylaxis. Recurrent migraine is rare in the elderly, and experience with these agents in this population is limited.

These drugs have been used effectively in patients with sympathetically maintained pain—specifically causalgia or reflex sympathetic dystrophy—according to anecdotal evidence. The oral drugs phenoxy-benzamine, prazosin, propranolol, and guanethidine should be considered only in unequivocal cases of reflex sympathetic dystrophy that have failed to respond to other measures.

Local anesthetics have become accepted for the treatment of diverse types of neuropathic pain. The preferred agent is mexiletine because of its relatively low risk of serious toxicity. Mexiletine is often tried as a second- or third-line drug after trials of antidepressants or anticonvulsants have failed. Treatment is initiated at 150 mg orally once daily. The dose is gradually increased (usually every 3 to 7 days) by 150 mg/day to a usual maximum of 300 mg tid. Conduction block is a contraindication, and the ECG should be monitored during dose escalation. Plasma concentration monitoring can also guide dosing.

Other drugs have been used in a variety of neuropathic pain states, despite little evidence of efficacy in controlled clinical trials. The risk of adverse effects, including parkinsonism and tardive dyskinesia, is relatively high in the elderly. Neuroleptics should be viewed only as second-line agents, to be considered in refractory neuropathic pain such as postherpetic neuralgia or painful neuropathy. Clinical experience is greatest with fluphenazine 1 to 2 mg orally bid to tid; haloperidol 0.5 to 2.0 mg orally bid to tid is sometimes used.

Anticonvulsants are advocated in neuropathic disorders characterized by paroxysmal or lancinating pain, a use supported largely by controlled studies of carbamazepine in trigeminal neuralgia. There are also some studies and many anecdotal reports of phenytoin, valproate, and clonazepam use in a wide variety of similar pain disorders, prescribed in the same dosage as that used to treat seizures.
Carbamazepine dosing in the elderly should be started at 100 mg orally bid, then increased gradually (by 100 mg/day) to the usually effective range of between 600 and 1800 mg/day in divided doses. A CBC count should be performed before initial dosing and again at 2 to 4 wk, 6 to 8 wk, and periodically thereafter. Phenytoin, with an oral loading dose of 500 mg once, 300 mg that night, and 300 mg on subsequent nights, may also be used. The initial dose of clonazepam is 0.5 mg/day, which is gradually increased; the usual effective dose is 0.5 to 3.0 mg bid. Valproate may be given at 250 mg once or twice daily and increased slowly (about every week by 250 mg/day in divided doses) to the usual range of 750 to 2500 mg/day in divided doses.
For all these drugs, doses should be increased until clinical efficacy or intolerance of side effects is achieved, or until plasma concentration exceeds the upper anticonvulsant range by a modest amount. Plasma drug levels should also be monitored, if possible, to judge compliance, to identify patients who rapidly metabolize the drug, to evaluate changes when other drugs are taken, and to document an effective plasma level. Although not an anticonvulsant, baclofen is classified with these agents because of its documented efficacy in trigeminal neuralgia. When it is used for lancinating pain in the elderly, treatment should begin at 5 mg orally bid, and dosage should be increased by 10 mg/day every other day until the patient is pain-free or side effects occur. While the neuroleptic pimozide can also be used for this indication, it is not preferred because of its high incidence of side effects.

Tricyclics are used in patients with neuropathic pain (eg, diabetic neuropathy and postherpetic neuralgia), chronic back pain, chronic headache, psychogenic pain, and others; one study has shown that imipramine is effective in relieving the pain of arthritis. Of those available in the USA, amitriptyline, clomipramine, desipramine, doxepin, imipramine, and nortriptyline have shown efficacy in clinical trials. Data are most compelling for amitriptyline, but like the other tertiary amines (clomipramine, imipramine, and doxepin), this drug has strong anticholinergic and sedative effects and may cause orthostatic hypotension. The secondary amine tricyclic antidepressants desipramine and nortriptyline are usually better tolerated than any of the tertiary amines. One of these drugs is often selected as first-line therapy in the elderly.
The regimens for all the tricyclic antidepressants are similar: initially, 10 mg at bedtime, increasing over several weeks to 50 to 150 mg at bedtime. Although analgesia often occurs at doses substantially lower than those required for depression, higher doses may be needed by some patients. Plasma levels can be monitored to determine whether poor results may be related to compliance or pharmacokinetic factors and to provide guidance during dose escalation.
These drugs should not be prescribed in patients with symptomatic urinary retention, narrow-angle glaucoma, or greater than first-degree heart block. They should be used cautiously in patients with mild dementia and in those receiving other drugs with similar side effects. A baseline ECG should be obtained, and another ECG should be obtained when the daily dose reaches about 150 mg; conduction or rhythm disturbances mandate dose reduction or discontinuance of the drug.
Structurally unrelated compounds (eg, fluoxetine, maprotiline, paroxetine, or trazodone) are sometimes administered as analgesics in patients unable to tolerate the first-line drugs or in those with relative contraindications to them. All have less anticholinergic effects, and fluoxetine and paroxetine do not cause weight gain, are much less sedating, and, in fact, can induce a CNS stimulatory effect. The literature provides less support for the use of these drugs. Since the analgesic effects of paroxetine have been demonstrated in controlled trials, it is most reasonable to select this drug as an alternative antidepressant for pain.