How do these medications compare to each other?

A group of German doctors retrieved and reviewed data from previous studies conducted for all three pharmacological therapies, totaling 17 studies and 7,739 patients who met the inclusion criteria. (Such a study is called a meta-analysis.)

Some of their sources included MEDLINE, SCOPUS, Cochrane Central Register of Controlled Trials, as well as unpublished data from FDA and NIH databases and others. Even though these studies may have some variations in how they were conducted, the amount of data reviewed was quite substantial.

(See our editorial note at the end of this article concerning the validity of meta-analyses such as this one.)

The article is written by Häuser W, et al, titled "Comparative efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome", and was published in the Journal of Pain, 11 (2010): 505-521.

One of the most remarkable findings in their analysis of these medications and their ability to reduce pain was that "adjusted indirect comparisons indicated no significant differences for 30% pain relief." This suggests that none of these were found to be highly effective against pain and they all seemed to be about the same, when evaluating degree of pain relief.

When combining pain and sleep disturbances, duloxetine (Cymbalta) and pregabalin (Lyrica) were found to be considerably more effective than milnacipran (Savella).

Milnacipran (Savella) and pregabalin (Lyrica) were more beneficial in reducing fatigue than duloxetine (Cymbalta), while duloxetine had a stronger impact on mood.

Both SNRI's caused more headaches and nausea/digestive symptoms and also raised blood pressure.

This comparison of specific features of these medications may be very helpful in a clinical setting as physicians try to select the most suitable treatment for each individual patient.

Though the level of pain relief or other noted improvements can be modest, or even minimal in some cases, drugs can still meet approval by the FDA. As mentioned above, pharmaceutical companies only need to show that a drug performs better than a placebo.

For example, Medical News Today reports the following data on clinical trials testing Cymbalta's effectiveness for FM: "Lilly established the efficacy of Cymbalta in two pivotal three-month clinical trials involving 874 patients with fibromyalgia. In both studies, Cymbalta reduced pain at study endpoint compared with placebo as measured by the Brief Pain Inventory (BPI) ... improvement in pain for Cymbalta vs. placebo was observed in the first week of each study. Fifty-one percent and 55 percent of patients on Cymbalta had a 30 percent improvement on the BPI at endpoint (clinically meaningful relief is considered at least 30 percent pain reduction)."

Some physicians are not convinced that all new drugs are better just because they are new, generally speaking, since this applies to treatments indicated for other conditions. The reason for their doubts is that the effectiveness/benefits of new drugs are not often compared to existing drugs.

In one unusual case, clinical trials for a new drug that was supposed to be promoted as another treatment for FM were abruptly terminated by Pfizer in February 2009. The "Musculoskeletal Report" (a source for Biopharm business news) announced that Pfizer had re-evaluated this drug, esreboxetine, and concluded its potential benefits to FM patients would not be too substantial.

The President and General Manager of Pfizer's Primary Care Business Unit, Pedro Lichtinger issued this statement, "While confident in the safety of these compounds, we don't believe that they provide significant benefit over other therapies."

Esreboxetine was a selective norepinephrine reuptake inhibitor that Pfizer, Inc. was working on for use in FM. It is thought to be essentially the same drug as reboxetine (Edronax), also made by Pfizer, but currently approved as a treatment for depression.

Though one can only speculate about the potential value this drug might have had for FM (or not), it becomes all the more evident that "head to head" trials (i.e., studies in which one drug is directly compared to another drug or drugs from the same class or group) might be the best way to demonstrate the advantage of one treatment over another.

Reference

Häuser W et al, "Comparative efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrom," Journal of Pain 11, no. 6 (2010): 505-521.