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Combining Drugs May Work Better in Fibromyalgia – ProHealth

Saturday, 6 May, 2017

Combining Drugs May Work Better in Fibromyalgia – ProHealth

So far as pain disorders go, fibromyalgia (FM) ranks right up there in nastiness. Estimates vary, but the highest estimates put rates of disability in FM at about 25%, far higher than in most other pain disorders (@10%).

There are no solutions for fibromyalgia yet. Recommended treatment protocols generally call for a multi-dimensional approach that includes drugs, physical therapy, behavioral interventions to calm a twitchy nervous system down and get better sleep, and exercise to induce an analgesic response.

Fibromyalgia may be amongst the poorest funded diseases, but it does have three FDA approved drugs. Lyrica was the first to be approved in 2007, followed by Cymbalta and Savella in 2009. Many other drugs - Drugs.com lists over 30 - are used in FM, and over time, a substantial database of their effectiveness is being formed.

Now comes an intriguing study that suggests that some people may have given up on the FDA approved drugs too soon.

Combination Drug Therapy for Fibromyalgia

Healthcare Costs and Medication Adherence Among Patients with Fibromyalgia: Combination Medication vs. Duloxetine, Milnacipran, Venlafaxine, and Pregabalin. Nicole M. Marlow, PhD, MSPH, Kit N. Simpson, DrPH, Ivana A. Vaughn, MPH, Ara Jo, MS, James S. Zoller, PhD, MHA, E. Baron Short, MD, MSCRc Pain Practice April 18th, 2017. 10.1111/papr.12585

These results suggest that patients in the combination therapy cohort were better able to achieve a therapeutic effect given the complementary pharmacologic activities of this treatment regimen, specifically a SNRI with pregabalin. The authors

The researchers - none of whom were allied with the pharmaceutical industry - looked at FM drug use and adherence over a three-year period in South Carolina. They included a long, long list of medications (opioids, anticonvulsants, SSRIs, SNRIs, anti-inflammatories, anti-migraine drugs, benzodiazepines, ADHD drugs, sedatives/hypnotics, muscle relaxants) in their study.

Their goal - to determine if FM patients who combined one of the big three FDA approved drugs (Lyrica, Cymbalta, Savella) with other drugs stayed on them longer than patients who were just taking the FDA approved drugs. Staying on the combo treatment longer presumably indicated that the drug combo was working. Dropping one of the drugs more quickly, on the other hand, presumably indicated that the drug combo didn’t work.

They also determined if medical costs went down. (Successful drug use often causes the numbers of doctor's visits and medical issues to go down.)

The study found that FM patients taking Lyrica, Cymbalta or Savella who also took another drug tended to remain on the drug combo longer than if they were just taking Lyrica, Cymbalta or Savella. That suggested to the authors that combining drugs was probably generally helpful in FM.

Increased adherence rates could be important because drug adherence rates in FM (because of side effects, lack of effect, and probably cost), to put it bluntly, suck. Adherence rates for Lyrica by itself bombed out at about 22% in this study. Savella adherence rates were better but still poor (31%), and Cymbalta's were a relatively decent 45%. Combining each of those drugs with another one increased adherence rates by about 60% in Cymbalta (34%) and 30% in Savella (43%) and rates in Cymbalta remained about the same (45%). Other studies have found similar adherence rates (Savella - 20%, Lyrica - 24%, Cymbalta - 45%.).

(The best dose to take? The highest adherence rates (@40%) for Cymbalta occurred at its highest dose of >60 mgs. Another study suggested that FM patients taking 60 mgs of Cymbalta had the best chance of having a good response. Lyrica (300 mgs) was next, followed by Savella (200 mgs) and then Lyrica again (150 mgs).)

Instead of going down overall, costs to the medical system went up for combination drug protocols. This was caused not by increased doctor's or ER visits or hospitalizations, but simply because the FM patients on combination therapies were taking more drugs and were staying on them longer.

Unfortunately, because the study was unable to assess pain levels or functioning, it was impossible to tell if some FM patients went on or stayed on the drug combos longer or simply because they were more desperate. In general, though, the authors noted that longer drug adherence is usually associated with better treatment outcomes.

This isn't the first study to suggest that it might be better to combine drugs than to fly solo in FM. A 2012 Spanish FM study found that the least effective course of action was to stay on one drug, and the most effective was to combine an antidepressant and an anticonvulsant. (For some reason, pain drugs were not included in the study.) Some sort of synchronicity appeared to be occurring; using these drugs together increased the effectiveness of the antidepressant drug by about 50% and the effectiveness of the anticonvulsant drug by 100%.

Adding Savella (milnacipran) to Lyrica more than doubled the rate of those responding to it (from 21-46%) in a 2013 open-label study. Another study found that pain relief was significantly greater for FM patients on both Lyrica and Cymbalta than for those using just one drug. The jump in the percentage of patients stating they'd attained at least moderate pain relief was startling. Sixty-seven percent (67%) of patients on the drug combo reported attaining at least moderate pain relief compared to 38.5% on Lyrica alone and 42% on Cymbalta alone. One potential downside of the drug combination, however, was increased drowsiness.

Another study suggested that if you're adding antidepressants to your drug mix, Paxil (paroxetine) might be the best option. FM patients on Paxil plus Lyrica had significantly lower symptom scores, tolerated their medications better, and reported more improved life satisfaction, mood, and sleep quality (P < 0.05) than FM patients taking Lyrica and either amytriptyline or Effexor (venlaxafine). Effexor, in particular, was poorly tolerated by the FM group.

Cymbalta First?

If you're going to focus on one FDA approved drug, which should you try? One rather massive study had some sobering news. None of the FDA approved drugs for FM by themselves reduced the number of doctor visits or hospitalizations or emergency room visits significantly. We've just seen, though, that adherence rates for Cymbalta top the big three FDA approved drugs for FM.

FM patients using Cymbalta also use the medical system less than those taking Lyrica. A 2014 study came to a similar conclusion: FM patients on Cymbalta saw the doctor less and spent less money on medical costs and took their medication more consistently than those on Lyrica. The possible flaw in that scenario? Doctors may be funneling their more severely ill patients to Lyrica.

Cymbalta demonstrates how easily drugs can transcend categorization. First approved for both depression and anxiety, Cymbalta has now been approved to treat neuropathic pain in diabetes, pain in fibromyalgia and osteoarthritis pain.

Taking the Older Drug Route

"All of these medications have been on the market for 15 years or more and have been widely used. They are all available as inexpensive generics and are at least as effective and safe as the other fibromyalgia medications." Consumer Reports

Or you might try older drugs. In 2014, Consumer Reports recommended that FM patients focus on effectiveness, safety and price and try these three older drugs first: generic amitriptyline (Elavil), generic gabapentin (Neurontin), Generic paroxetine-IR (immediate release Paxil). (Lyrica is an updated version of gabapentin.)

Other Possibilities

Medical Marijuana and low dose naltrexone are two less mainstream medications that fare very well in patient surveys.


The current batch of FM drugs is hardly the cat's meow. This and other studies suggest, though, that if you're going to go the drug route that combining them - perhaps in lower doses - may be better. This study found that fibromyalgia patients who used FDA approved drugs in combination with other drugs stayed on them longer than patients on mono-therapy.

Source: Combining Drugs May Work Better in Fibromyalgia - ProHealth

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