Combining Drugs May Work Better in Fibromyalgia

Reprinted with the kind permission of Cort Johnson and Health Rising.

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 – 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.

About the Author: ProHealth is pleased to share information from Cort Johnson.  Cort has had myalgic encephalomyelitis /chronic fatigue syndrome for over 30 years. The founder of Phoenix Rising and Health Rising, he has contributed hundreds of blogs on chronic fatigue syndrome, fibromyalgia and their allied disorders over the past 10 years. Find more of Cort's and other bloggers' work at Health Rising.

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2 thoughts on “Combining Drugs May Work Better in Fibromyalgia”

  1. FibroSocietyTara says:

    Perhaps there were no opioids mentioned in the study, because they’ve become as taboo as smoking?! South Carolina has, supposedly, got a pretty terrible illegal OxyContin problem.
    So, I’m assuming that any Government sponsored (all or in part) is heavily discouraging the use or even mention of these forms of pain relief.
    But, let’s face it. If you want to do anything besides lay in bed for the rest of your life with “FibroPhobia” (with good reason) you’re going to want something for breakthrough pain! Lyrica (hand, face, foot swelling joke), cymbalta (electrical jolts over your skull) and Savella (tolerable if you’re spared the headaches and the pharmacy doesn’t run out of it) are just there to appease most pain management doctors. I’m not sure they even work, but I’m on one. But you can bet your sweet but I’m also on a long acting Opioid and a very low dose immediate acting one for breakthrough. Forget the anti-inflammatory, there’s no point in torturing your stomach or liver/kidney any further.
    The CDC groups all Opioid users, even legal prescription carrying ones, in their statistics with corner buying, grandmother bludgeoning, jailbird gangster tattooed hunkers!!
    And that’s why they’re not in the report.
    Doesn’t matter if they’ve saved your life as you know it. Our government thinks they know better than the Doctor you’ve been seeing for 10 years. They’re even threatening your pharmacist.
    Ok, you’ve been told, soapbox being returned to its storage place…..
    Good luck, check your vitamin levels and don’t accept your first FM diagnosis…

  2. CarolBuck says:

    I teach a free class about fibromyalgia, in which I use research I find online, especially articles I find on ProHealth. The recent article I found on combining drugs is absolutely correct, at least for my skin disorders. I’ve had 3 disorders so far, one related to fungus, a second to bacteria, and a third, my current one, to allergy. My dermatologist’s associate, after being frustrated by not being able to get results with the prescribed medications, decided to combine the Fluocinonide gel and Mupirocin cream. That has been the only thing that has worked. My skin is now clearing up rapidly.

    However, the article’s reference to Lyrica really disturbs me. I have had 9 students who were prescribed Lyrica, and all of them were fine for the first 4 months. Then, something of a nightmare began for all of them. Lyrica, if I remember correctly, is to be used only for 2 weeks at a time. But, doctors seem to be prescribing it for full-time use. After it starts causing problems, the doctors told their patients to slowly cut back, and then cut out all together, the use of Lyrica. This caused the nightmarish reaction of heavily increased pain in all of my students, plus other extreme difficulties. It took several months fpr them to completely wean them off the drug. Since the problems seem to occur with all the fibromyalgia sufferers I’ve dealt with, I recommend that they stay away completely from Lyrica and try a more “natural” approach, starting with blood tests for vit. D-3 levels and any metals toxicity. I also recommend that they try, with their doctor’s supervision, a combination of B vitamins, starting with low doses, as well as coQ10. The levels can be increased carefully, along with a frequent check on how their blood levels are doing. I never recommend mega-doses of vitamins, since no one knows how that will affect the human body. Doses over 10,000 IU’s of D-3 are used as rat poison and are not recommended. I also recommend pacing themselves in whatever they do, especially when exercising or cleaning, as well as using white vinegar for cleaning most things. One unusual thing I recommend is to use the natural items carefully. My doctor found that Oregano Oil, when used as an antibiotic, can heavily damage the liver. I can tell you from my own experience that it takes a long time to heal. I also warn everyone to be careful about using products that have concentrated glycerin, in any form. Millions seem to have severe allergic reactions to that.

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