Treatment of patients with fibromyalgia (FM) is currently showing difficulties. The different treatments being used have not yet obtained the satisfactory results expected which is why patients with FM continue to maintain the same clinical manifestations even many years after being diagnosed.1

Pharmacological treatment options are quite broad because many drugs that act on the central nervous system may have beneficial effects in these patients.2,3 Analgesic, anti-inflammatory drugs (NSAIDs), antidepressants, anticonvulsants, benzodiazepines and other drugs that act on the central nervous system are used as the first line treatment in patients with FM, although in most cases are not directed towards the treatment overall disease, but only to address some of the symptoms.

However, due to the many adverse effects of these drugs also, one must be aware of what they can each contribute to the treatment of fibromyalgia and prevent overmedication, a problem often seen in these patients.

On the other hand, there are no studies to determine what type of drug is most effective, or what sequence or association should be used to obtain the best possible results.

Therefore, in this situation, when administering a drug to treat fibromyalgia not only choosing among several possibilities is the responsibility of the physician, but also knowing what strategy is the most effective.

The aim of this paper is to analyze the different strategies of drug treatment followed by rheumatologists specializing in the treatment of patients with FM and determine which ones are most effective.

We included 232 patients in the analysis, 98% women, mean age 47.7±8.6 years and duration of disease 4.3±4.0 years. All physicians provided approximately the same number of patients per study.

The number of drugs to treat FM was 3.1±1.6 drugs/patient at the initial visit, with the distribution shown in Table 1. After treatment the number of drugs rose to 3.4±1.9 drugs/patient (P<.017) in the final visit. The major changes between the two visits occurred between NSAIDs, antidepressants, benzodiazepines and anticonvulsants (Table 1).

For further analysis we only took into account drugs that act directly on the central nervous system and analgesics and NSAIDs were discarded. Moreover, the consumption of hypnotics has added the use of benzodiazepines, since in many cases they are also used to induce sleep.

The most significant changes were: an increase in the number of antidepressants, from 0.50±0.50 to 0.71±0.45 (P<.0001) antidepressants/patient an increase number of anticonvulsants, from 0.14±0.35 to 0.41±0.49 (P<.0001) anticonvulsants/patient, and a reduction in the number of benzodiazepines, from 0.48±0.50 to 0.38±0.48 (P<.001) benzodiazepines/patient. Regarding the number of drugs introduced into treatment only one was introduced in 87 patients in 15 patients 2 were entered and in 4 patients 3 drugs were introduced simultaneously.

From the point of view of clinical manifestations, there was a significant improvement between the initial and the final visits affecting the emotional and physical factors, active coping and overall score in the total group of patients.

In this paper we have analyzed some of the most common strategies of drug administration followed by a group of physicians with special attention to the treatment of patients with FM, in conditions of medical practice. The results suggest that certain changes in the drug delivery strategy are accompanied by significant changes in clinical status of patients.

As a general strategy, there was a significant increase in the total number of drugs used to treat patients and more often involve the introduction of a single drug.

Some of the treatment strategies were used more often than others by the physicians of this study, and among them, strategies to individually incorporate an antidepressant, an anticonvulsant or both drugs simultaneously were clearly more frequent. Other strategies, for example stopping benzodiazepines, were used, and although there were indications that it may also be beneficial, it could not be tested due to the small number of patients in this situation since this strategy was accompanied, often, in exchange for some other drugs.

However, the strategy of not making changes to the treatment was the most frequent of all affecting 36% of patients. However, in these patients the clinical evaluation of the initial and final visits showed no significant differences in the clinical situation of patients.

There remains considerable skepticism regarding FM8 and a fairly widespread opinion among physicians is that drug treatment does not provide much benefit so the patients are often only treated with drugs to treat symptoms of pain, mainly analgesics and NSAIDs.

One possible explanation may lie in the fact that in the European Union there is no indication of drug treatment in FM, while in the U.S., the FDA3 has approved 2 drugs, dual antidepressants and inhibitors of serotonin and norepinephrine (duloxetine and milnacipram), and an anticonvulsant drug (pregabalin) for this indication. Therefore, in the European Union, these drugs can only be given when dealing with clinical manifestations for which they are approved; however, in many FM patients these clinical manifestations are not exactly the most relevant.

In this sense, the finding in our study that the only difference between patients to whom drugs were introduced and those to which the drug was discontinued, emotional factors, which measure anxiety and depression, confirm that these drugs were prescribed to treat these symptoms and not others such as pain, fatigue, and functional capacity as measured by the physical factor.

A meta-analysis has shown that various recent9 antidepressants produce a particularly favorable effect on pain, sleep, mood, fatigue and mood status changes, but with a low effect size in relation to perceived quality of life. Something similar happens with anticonvulsants, which have also shown that there is a degree of hard evidence that pregabalin and gabapentin produced improvement in pain and sleep, but not on fatigue or mood alterations.10

In our work we found that administration of an antidepressant or an anticonvulsant individually improves the patient's general condition with a moderate effect size. However, when added both at the same time the effect size increases by almost 50% compared to antidepressants and up to 100% with respect to anticonvulsants. This finding is consistent with that recently suggested by some authors.11

However, we cannot rule that the mere change of drug treatment, adding 2 new drugs, could have a positive impact beyond their specific effect. The change itself and the expectations of the patient before can have a therapeutic effect.12

It is noteworthy that the major effect of these drugs occurs precisely on the physical factor of ICAF followed the emotional factor. The factors of active and passive coping did not change significantly, as there are ways in which patients cope with the disease and are not modified in the short term by the introduction of a drug.6

The criterion to follow a particular strategy has not been entirely uniform among physicians in the study. Thus, the strategy to not modify the treatment was followed by physicians in 36% of patients despite their clinical situation in terms of degree of impairment was similar to that of other patients who used other strategies. However, within this group of patients, 74% were receiving one or more drugs so the scope for any type of change was large.

Moreover, there was a similar number of patients to whom only benzodiazepines were suspended or added, suggesting that some strategies are not shared unanimously by all physicians.

The main limitation of this study is that it has not been able to evaluate all possible strategies of drug administration but only those most frequently followed by doctors, and we cannot conclude on which is the most effective strategy. Originally the study was not designed for it so the results are only for guidelines on clinical practice in the sample of clinical units involved in the study.

Another limitation is that some variables were not analyzed in this study and yet may behave as potential confounders. Variables such as comorbidity, or treatment followed for this, and were not evaluated in our study and may affect results obtained in relation to the effectiveness of different strategies.

Although it initially was not recommended that researchers change the preconditions of psychological therapy or physical exercise, it is possible that over the 3-month follow-up study period there was some sort of modification that may have influenced the results.

We note that the importance of this study is that it allows us to know which are the main strategies of prescription drugs for fibromyalgia patients followed in our environment and in conditions of medical practice. Although data from our study cannot ensure the best possible strategy, we found some evidence to suggest that among the most common strategies some of them might be superior to others. These findings should be tested in future studies.

This study was financed by the Fondo de Investigación Sanitaria (FIS)PI 07/0202, of the Health and Consumption ministry.

Pfizer Pharmaceuticals contributed economically to the development of the ICAF project as a research Project of the Spanish Foundation for Rheumatology. The 3 authors of the study have been principal investigators of the ICAF project.