By Richard Podell, MD, MPH
Flexeril (cyclobenzaprine) is FDA approved for the short term relief of “muscle spasm associated with acute, painful muscoskeletal conditions.” It’s not approved for long term usage or to treat fibromyalgia (FM).
Still, fibromyalgia specialists sometimes prescribe Flexeril for use as a sleeping aid and to reduce fibromyalgia pain. But at standard doses, Flexeril’s sedating effect often carries over to the next day, worsening fatigue.
There may be a better way of prescribing Flexeril; not only a way that improves sleep and pain, but to actually lessen feelings of daytime fatigue also.
Two key innovations:
Taking a lower than usual dose of Flexeril at night in the 2 mg to 5 mg range instead of the usual 10 mg dose.
Taking Flexeril every night for many weeks, not just as an intermittent sleeping pill.
The lead author of this key research study is Harvey Moldofsky, M.D., now Professor Emeritus at the University of Toronto. Dr. Moldofsky’s career-long research on fibromyalgia has provided major contributions to understanding our field. For example, Dr. Moldofsky’s 1975 article was the first to prove the relationship between fibromyalgia pain and abnormal patterns of sleep. His most recent publication on fibromyalgia was in 2015.
In a 2011 study , Dr. Moldofsky’s Toronto team conducted a double-blind study of 36 patients with FM. Half were given “low dose” Flexeril/cyclobenzaprine starting at 1 mg and working up to the 4 mg range. The others received a placebo. These were taken every night for over eight weeks.
Low dose cyclobenzaprine made a positive difference, with very few major side effects. Patients on the placebo did not improve.
Here are the main numbers:
PAIN: Pain intensity levels were scored prior to starting treatment and after eight weeks. For the Flexeril group, pain severity decreased by 26.1%. The “P value” was less than .01. (That is, the probability (P) of this result being obtained by chance was less than one chance in 100. A P value of <.05, is considered to be “statistically significant.”) The placebo group had no change in their pain.
DAYTIME FATIGUE: For those taking Flexeril, daytime fatigue scores decreased by 14%. This difference was statistically significant (P=.039). For those on a placebo, daytime fatigue did not improve.
SLEEP: Patients taking Flexeril increased their average sleep time by about one-half hour. Those on a placebo slept about the same as they did before. Flexeril may also have improved the quality of sleep by reducing the occurrence of disruptive brain wave patterns.
ANXIETY/DEPRESSION: After eight weeks, patients taking low-dose Flexeril improved on their anxiety/depression score by 24.1%. (P=.012). The placebo group’s anxiety/depression score decreased also but by just 3.8%.
After eight weeks, patients were asked to rate whether they had improved since starting treatment. Those taking low-dose Flexeril tended to rate themselves as improved (P=.001). Those taking a placebo did not. The treating doctors (who did not know which group the patient was in) agreed that the Flexeril patients had improved, while placebo patients had not.
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Side effects in this relatively small study were mild and occurred about as often in both groups. The only adverse event that was rated as severe was a headache. This occurred in a patient taking the placebo.
Beyond this study, the most serious potential side effect for Flexeril (cyclobenzaprine) is prolongation of the QT interval  on the electrocardiogram. This can be important since a long QT interval increases the risk for serious heart rhythm problems.
In fact, a fair number of medicines also increase the QT interval. Among these are antibiotics (e.g. Zithromax, Biaxin, Cipro, Levaquin); heart medicines (Amiodorone, Flecainide); several cancer medicines; anti-nausea drugs (Odansetron/Zofran, procholorperazine/Compazine); many antipsychotic medicines, and tricyclic antidepressants such as Elavil (amitryptiline), or Pamelor nortriptyline). One would usually avoid combining these medicines with Flexeril. Clinicians might consider which patients should have an EKG read out of their QT interval.
Other commonly used medicines tend to increase the blood level of Flexeril/cyclobenzaprine, thereby increasing Flexeril’s effect on prolonging the QT interval. This interaction is most likely for medicines that compete with Flexeril for the same liver detoxification pathways.
Persons with liver disease, certain heart rhythm abnormalities or a known prolongation of their QT interval might best avoid Flexeril (and other drugs that prolong the QT interval).
Take Home Thoughts
As medicines go, Flexeril at 5 mgs (the lowest commercially available dose) is relatively safe and relatively inexpensive. Therefore, if you have fibromyalgia, consider discussing an option like this with your clinician:
Perhaps start with a 2.5 mg dose at night (one half of a 5 mg pill). If 2.5 mgs doesn’t make you too tired the next day, then consider increasing to 5 mg each night for an eight week-long trial. If 5 mg makes you tired, go back to 2.5.
Don’t prejudge whether Flexeril actually helps until the full trial is done.
(I contacted Dr. Moldofsky, who said that in his study there were no interim measures of effectiveness taken between baseline and eight weeks. My guess is that the maximum benefit from low dose Flexeril would take more than a few days to be noted, but fewer than eight weeks.)
Your doctor probably has not memorized all of the potential interactions of drugs you may be taking and Flexeril, but your pharmacist’s computer should know. Ask your pharmacist specifically whether any of your medicines increase the QT interval and whether any of your medicines use the same liver pathways as Flexeril (Cytochromes P450 3A4 or P450 1A2, or to a lesser extent P450 2 D6).
Richard Podell, M.D., MPH, is a graduate of Harvard Medical School and the Harvard School of Public Health. He has been treating patients with ME-CFS and Fibromyalgia for more than 20 years.
A clinical professor at New Jersey's Robert Wood Johnson Medical School, Dr. Podell see patients at his Summit, NJ and Somerset, NJ offices. His website is DrPodell.org