Dr. Sterling West
The strongest evidence of efficacy exists for the Food and Drug Administration–approved drugs duloxetine, milnacipran, and pregabalin, along with the off-label agents venlafaxine, gabapentin, cyclobenzaprine, and the tricyclic antidepressants. All of those off-label drugs are supported by a body of literature supporting effectiveness, and they make for good alternatives when patients can’t afford the approved drugs, which are invariably more costly, he said.
The numbers-needed-to-treat to achieve a 30% reduction in pain have been calculated at 7.2 for duloxetine, 8.6 for pregabalin, and 19 for milnacipran.
"All of these patients with fibromyalgia come to us with pain," Dr. West noted. "I choose their medications based on what their chief complaint is."
For example, a fibromyalgia patient who presents with pain, prominent fatigue, and depressed mood is a good candidate for duloxetine (Cymbalta), which fortuitously is also approved for osteoarthritis pain. A patient who complains of pain, cognitive dysfunction or "fibrofog," and fatigue may do well with milnacipran (Savella) starting at 12.5 mg in the morning with food, titrated upward by 12.5 mg per week to a maximum of 50 mg b.i.d. Pain with sleep disturbance is a symptom cluster that often responds well to pregabalin (Lyrica), dosed at 50 mg with food before bed, increased by 25 mg/day weekly to at least 150 mg/day before a morning dose is added, with a ceiling of 225 mg b.i.d..
Tramadol is supported by "modest" evidence of efficacy as an add-on niche medication for patients with substantial pain despite their baseline medications, the rheumatologist continued. Its efficacy in fibromyalgia is not through its better-known mu-opioid receptor agonist effect, but rather through the mechanism of serotonin-norepinephrine reuptake inhibition. Dr. West said that he starts tramadol at 25 mg/day and increases it weekly to a maximum of 100 mg four times daily.
Rational combination therapies utilizing different mechanisms of action and that are backed by supporting efficacy data include milnacipran plus pregabalin, venlafaxine and gabapentin, and fluoxetine and either amitriptyline or cyclobenzaprine, the rheumatologist continued.
Nearly all the medications recommended for treatment of fibromyalgia other than pregabalin and gabapentin modulate serotonin. That means patients need to be monitored for the development of suicidal ideation as well as serotonin syndrome. A simple way to check for emergent serotonin syndrome is to regularly evaluate the patient’s deep tendon reflexes.
"If a patient suddenly becomes much more hyper-reflexive, you need to start dialing it down because you’re putting them at risk for serotonin syndrome," Dr. West cautioned.
It’s evident that many physicians are struggling with the use of medications to treat patients with fibromyalgia. "There’s a gap between the evidence and what medications are actually prescribed in practice," Dr. West observed.
This gap was highlighted by data from the REFLECTIONS study, presented at last year’s annual scientific meeting of the American Pain Society. REFLECTIONS is an Eli Lilly–sponsored longitudinal study of 1,700 fibromyalgia patients and 91 physicians. The physicians collectively prescribed 186 different medications to treat individuals with fibromyalgia. Only about one-quarter of the physicians used one of the FDA-approved drugs. Opioids and nonsteroidal anti-inflammatory drugs were used just as frequently, even though these medications have zero evidence of efficacy in fibromyalgia and experts agree they are of no help.
Dr. West reported having no financial conflicts.