Robert I. Fox, MD, PhD

Disclosures

May 20, 2009

Question

What do you recommend for pain relief in a 57-year-old woman with primary Sjögren's syndrome and severe osteoarthritis? Pain is caused by spinal stenosis, facet joint syndrome, and fibromyalgia. The patient is allergic to aspirin, sensitive to nonsteroidal anti-inflammatory drugs and drugs that cause dry eyes, and is beginning Forteo® injections.

Response from Robert I. Fox, MD, PhD
Professor and Member, Scripps Memorial Hospital and Research Foundation; Rheumatologist, Scripps Memorial Hospital, La Jolla, California

This is a complex situation. The patient has several different sources of pain, including fibromyalgia, spinal osteoarthritis, and perhaps a past compression fracture. Several variables influence the options for pain control in this patient, including Sjögren's syndrome and sensitivity to nonsteroidal anti-inflammatory drugs.

The nature of the patient's intolerance to aspirin and nonsteroidal anti-inflammatory drugs is not explained. Some patients with aspirin sensitivity who do not tolerate cyclooxygenase (COX)-1 agents can tolerate a COX-2 drug such as celecoxib (Celebrex®), which achieved significant pain relief in the dental analgesia model.[1] However, it should be remembered that COX-2 drugs reduce, but do not eliminate, gastric bleeding.[1,2]

With respect to Sjögren's syndrome, the associated fibromyalgia presents a difficult challenge due to the anticholinergic side effects of many medications, such as the tricyclic antidepressants. Recently, the US Food and Drug Administration approved pregabalin (Lyrica®)[3] and duloxetine (Cymbalta®)[4] for treatment of fibromyalgia. In some patients, these drugs may produce significant anticholinergic side effects, particularly when used at higher doses. Therefore, some chronic pain management centers and rheumatologists are prescribing a combination of pregabalin 75 mg and duloxetine 30-60 mg at bedtime.[5] This regimen appears to be better tolerated and has fewer side effects than the higher doses of duloxetine (which causes gastric toxicity and anticholinergic effects) or pregabalin (which causes weight gain) alone.

The approach to chronic pain includes opioid as well as nonopioid drugs. In our clinic, we have found that tramadol (Ultram®) seems to be well tolerated in many patients and is very effective.[6] Traditional opioids have the expected side effects of constipation, mental fogging, and risk for dependency. Surprisingly, low-dose naltrexone (an opioid antagonist) may also offer pain relief.[7]

The development of newer classes of antidepressants and second-generation antiepileptic drugs has created unprecedented opportunities for treating chronic pain.[8] These drugs modulate pain transmission by interacting with specific neurotransmitters and ion channels. The actions of antidepressants and antiepileptic drugs differ in neuropathic and nonneuropathic pain, and agents within each medication class have varying degrees of efficacy.

Novel antidepressants (ie, bupropion, venlafaxine, duloxetine) are effective in the treatment of neuropathic pain. The analgesic effect of these drugs is independent of their antidepressant effect and appears strongest in agents with mixed-receptor or predominantly noradrenergic activity, rather than serotonergic activity. First-generation antiepileptic drugs (eg, carbamazepine, phenytoin) and second-generation antiepileptic drugs (eg, gabapentin, pregabalin) are also effective in the treatment of neuropathic pain.

In summary, the efficacy of antidepressants and antiepileptic drugs in the treatment of neuropathic pain is comparable. Tolerability is also comparable, but safety and side effect profiles differ. Tricyclic antidepressants are the most cost-effective agents, but would not be tolerated in this patient. Second-generation antiepileptic drugs are associated with fewer safety concerns in elderly patients. Although the antidepressants have documented efficacy in chronic low back pain, their benefit is rather limited.

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