Chronic pain syndromes, such as the fibromyalgia syndrome (FMS), have a significant impact on quality of life and lead to decreased productivity.1–3 The main manifestations of the syndrome are widespread musculoskeletal pain, presence of allodynia and hyperalgesia, often accompanied by sleep disturbance, anxiety, depression, headaches and irritable bowel syndrome, among others.4

The worldwide prevalence reported for FMS is between 3% and 5% of the adult population (20–60 years old), with a significant prevalence in women. In Mexico, the estimated frequency is 0.68% (95% CI, 0.56–0.80).5

The negative impact of FMS is manifested in the daily activities of life and result in lost work and/or school, with an effect on productivity, a reduction that has been estimated up to 65%. Thus, the most important economic impact of FMS occurs in the costs associated with lost productivity, which represent up to 70% of the burden of disease.6 The therapeutic approach for FMS is multidisciplinary and the main objective is to reduce pain and improve functional capacity. Treatment should include: patient education, lifestyle changes, physiotherapy and drug treatment.7

The most frequently studied pharmacological treatment is the use of tricyclic antidepressants. A recent meta-analysis analyzing effect size in reducing pain with amitriptyline in FMS calculated a standardized mean difference (SMD) of −1.64 (95% CI, −2.57 to −0.71).8 Given the high incidence of adverse effects associated with use of tricyclic antidepressants and seeking a better safety profile, selective inhibitors of serotonin reuptake inhibitors (SSRIs) have been an alternative treatment. The same meta-analysis reported a SMD, in the case of pain when using fluoxetine and paroxetine, of −0.39 (95% CI, −0.77 to −0.01) and when treating with selective inhibitors of noradrenaline (SINA) the authors reported an SMD for duloxetine and milnacipran of −0.36 (95% CI, −0.46 to −0.25).9

The combination of at least 2 drugs with different modes of action has also studied. The analgesic effect documented with the combination of tramadol with acetaminophen has identified a reduction of at least 50% of the baseline pain score in 35% of cases and the combination of drugs is well tolerated and showed significant improvement in functionality as measured by the fibromyalgia impact questionnaire (FIQ).10 Furthermore, the combination of amitriptyline and fluoxetine reported larger improvement in FIQ and VAS scores compared to the use of monotherapy.11

Other alternatives are the newly identified auxiliary a2-δ subunit ligands of calcium voltage-dependent channels in the CNS (pregabalin, gabapentin). Several clinical trials have reported a significant improvement of pain in patients with FMS, but also improved functionality, mood and a reduction in sleep disturbances. On the other hand, data from clinical trials have been integrated into a meta-analysis showing a modification of the SMD for pain of −0.28 (95% CI, −0.36 to −0.20), improvement in sleep disturbance of −0.39 (95%, from −0.48 to −0.39) and improved quality of life of −0.30 (95% CI, −0.46 to −0.15).12 It is noteworthy that the Food and Drug Administration has approved at least 3 drugs for the treatment of FMS: pregabalin (in 2007), duloxetine (in 2008) and milnacipran (in 2009).13

One of the problems faced by patients in any health system is access to effective drugs. Many assistance programs are designed with high levels of evidence, but also a policy of cost containment, depending on the availability of often limited resources. Thus, the objective of this study was to identify which of the available drug treatments in the public health system in Mexico for the treatment of FMS is the most cost-effective.

We performed an economic analysis of the cost-effectiveness rate, with a Markov model construct used to compare the costs and efficacies of alternative first-line drug available in Mexico for the treatment of FMS.

Economic Model

The most important symptom of FMS is chronic pain and its impact is mainly on functionality and quality of life. For the purposes of the model we used the information available through the visual analogue scale (VAS), where 0 represents no pain and 10 the most intense pain imaginable. The functionality in FMS was determined through the FIQ, which measures a multidimensional health status of patients. The FIQ scores are between 0 and 100, where 0 represents the highest functional capacity and 100 the worst state of health.15 The Markov model employed was adapted from a published study by Tarride et al.16 While the model mentioned above was designed for another indication (neuropathic pain), different from the present analysis, the inclusion of VAS as a determining factor in assessing the severity of pain has been widely recommended for the evaluation of patients with fibromyalgia according to current literature.17 On the other hand the assumptions of model were similar, with adult patients ≥18 years of age, diagnosed with fibromyalgia and men and women with chronic musculoskeletal pain. Patients were treated throughout the cycle or the end of the observation period (12 months). According to the natural history of disease we did not consider a risk of death associated with FMS and also not did not consider treatment changes throughout the observation period.

The basic model is shown in Fig. 1. There are 3 health states defined by VAS scores: no pain or mild pain (VAS<4 points), moderate pain (VAS 4–7 points) and severe pain (VAS>7 points). Patients entered into the model had moderate to severe pain. The probability of moving to a lower state of pain was identified by modifying the baseline VAS to a decrease in pain of 50% as a result of treatment and a decrease in the FIQ of 30%. The probability of migrating to a state of worst pain was considered treatment failure, which is a function of loss of effectiveness or treatment discontinuation due to intolerance to adverse events, and these were considered for the cases of antidepressants, anticholinergic, serotonin and gastrointestinal effects as well as dizziness and drowsiness produced by ligands of the a2-δ auxiliary subunit receptors. The cycles of the model were defined by periods of 3 months for a total time horizon of 12 months and 4 cycles were built.

Figure 1.

Markov model of the health stages of the fibromyalgia syndrome.

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Source: authors, from Tarride et al.16.

The baseline case results are shown in Tables 3 and 4. In relation to the expected costs for the first year of treatment, the lowest cost was obtained for treatment with amitriptyline ($ 9047.01), followed by fluoxetine alone ($ 10,183.89) and fluoxetine in combination with amitriptyline ($ 10,866.08). The duloxetine alternative was more expensive ($ 28,768.49).

By identifying the health outcomes, the probability of achieving a reduction of VAS over 50% of its baseline score (Table 3) was higher with pregabalin (44.8%), the next best alternative was gabapentin (38.1%) and duloxetine (34.2%). The alternative treatment to lower effectiveness in reducing the VAS score was fluoxetine as monotherapy (6.2%). When analyzing the percentage reduction in the FIQ scale (Table 4), the largest proportion was reached with pregabalin (31.6%), followed by gabapentin (29.1%) and duloxetine (28.5%). The alternative treatment that reached a lower overall improvement measured by the FIQ was fluoxetine as monotherapy.

Treatment with pregabalin, gabapentin or duloxetine have better results in the modification of the VAS and FIQ, but are more costly than its comparator, amitriptyline. Of these 3 comparators, pregabalin provides better clinical outcomes at a lower cost, absolutely dominating gabapentin and duloxetine.

Analysis of net savings per capita, on the horizon of 3, 5 and 10 years, is presented in Table 5; the data show the difference in costs and changes in the FIQ to be gained by treating patients with pregabalin, gabapentin or duloxetine, in relation to expected with regular use of amitriptyline over time. It is seen that in none of these cases there are savings. However, among these 3 alternatives, pregabalin treatment proves to be a saver with greater global improvement at a lower cost at 3, 5 and 10 years of treatment.

In the probabilistic sensitivity analysis, to construct acceptability curves, from a level of willingness to pay $ 50000 (≈U.S. $ 3850; exchange rate: 13.0 pesos per U.S. dollar) for one additional patient to succeed in changing the VAS, pregabalin is a cost-effective alternative in 80% of cases. The curve is shown in Fig. 2. For measuring the effectiveness of the percentage reduction of FIQ, with a willingness to pay $ 75000 (≈ U.S. $ 5770) for one additional patient, the total improvement cost for pregabalin is effective in 70% of cases (Fig. 2).

Figure 2.

Cost-effectiveness acceptance curves of pregabalin vs amitriptyline in the treatment of fibromyalgia. VAS: Visual analog scale; FIQ: fibromyalgia impact questionnaire.

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Chronic pain syndromes, especially those of musculoskeletal origin, have been addressed in health services, as they have increased as a complaint, affecting the economically active population and represent a high impact in terms of direct, indirect and even non-tangible costs.

Our results show that the best clinical effect of treatment of FMS is expected with the use of duloxetine, gabapentin and pregabalin. Of the 3 alternatives, pregabalin achieves the highest proportion of patients with clinical success for pain control (44%) and the greatest impact on the overall improvement measured by FIQ functionality (31%). Also among the three, pregabalin leads to lower costs.

Thus, in the comparison between these 3 treatment options for FMS, pregabalin dominates absolutely, providing better clinical outcomes at lower costs. By comparing pregabalin with standard treatment, which in this case corresponds to amitriptyline, the former leads to better clinical outcomes but at a higher cost. The additional cost, the system will have to assume for one additional patient in order to reach better pain control and improved functionality, is between $ 50000 and $ 75000 dollars annually. In a hypothetical level of willingness to pay $ 50000 for one additional patient for adequate pain control and $ 75000 for overall improvement, pregabalin is a cost-effective alternative in 60% and 80% of cases, respectively, for the treatment FMS in the public health system in Mexico. It is correct to say that Mexico has not yet accepted cost-effectiveness thresholds as measures of effectiveness as used in this investigation, nor have these been seen by other authors. However, it is worth mentioning that levels of $ 50000 or $ 75000 are below the GDP per capita in the country (≈ $ 130000/U.S. $ 13900),32 so that even under these parameters, the results of the research indicate that the alternatives would be highly cost-effective, as suggested by the World Health Organization.33

The data obtained in this study are similar to those reported by Choy et al.34 who performed a model for the health system in the UK, where the comparators used were amitriptyline, duloxetine, tramadol and gabapentin. In the latter model it was estimated that with a willingness to pay 30000 pounds per year of life adjusted for quality of life (QALY), pregabalin is a cost-effective alternative in 60% of cases. On the other hand, a recent study in the United States of America,35 which analyzed the use of duloxetine versus routine treatment, showed an incremental cost-effectiveness per QALY gained of about U.S. $ 47500 as a first-line treatment and U.S. $ 16565 as a second-line treatment in a 2 year time horizon. In this regard it is consistent with our analysis and duloxetine could be an second line option, since our study, the ICER of this alternative was high in comparison to pregabalin.

The medical literature shows little in relation to economic analyses for FMS, and there are other models made for non-drug alternatives that are shown to be cost-effective compared with placebo and require additional infrastructure.36,37 In the data shown in both the UK and Mexico, there is consistency with this pharmacoeconomic behavior, so it can be taken into account as a viable alternative for the treatment of FMS. It is important to consider that even if the perspective with which we worked in the study considered only direct costs, social responsibility with health institutions to reinstate the individual to his or her workplace and restore the quality of life of patients may justify the additional costs necessary to use new treatment alternatives.

The limitations of this study are related to the construction of a model which attempts to represent the reality of the clinical course of FMS and the potential changes associated with different treatments compared. The model is fed information from external sources, so there is no joint distribution of costs and clinical outcomes, and also there is no “face to face” comparison between the various treatment alternatives. However, tests were conducted to ensure that the information contained in the model had sufficient internal validity to be taken into account and in this way, the biases found in the results of this research are those associated with the publications themselves, without a differential bias for any of the treatment alternatives compared.

The information obtained from this economic evaluation between drug alternatives for the treatment of FMS may be useful to support decision makers in health systems similar to institutions offering public health services as in Mexico.

Pfizer S.A. de C.V financed the present study.

Pfizer S.A. de C.V financed the present study without this generating any legal or result compromise. Upon reviewing the manuscript Dr. Joaquín F Mould Quevedo was an employee of Pfizer S.A de C.V.