Current Treatments for Fibromyalgia

Medication Therapies

There is no cure for fibromyalgia. Treatment is focused on symptom relief and requires a multidisciplinary approach. Choice of treatment is based on patient-specific symptoms and optimally should include medication used in conjunction with non-pharmacologic interventions, both physical and psychological. Over-the-counter medications such as acetaminophen or NSAIDs are peripherally acting and not effective for the symptom management of fibromyalgia pain, but they can be used to treat the pain triggers involved in fibromyalgia.² NSAIDs and acetaminophen are most helpful in people who have comorbidities such as arthritis.

As opioid use has increased dramatically in the treatment of chronic pain in the last 20 years, its use has also dramatically increased in this patient population.¹²⁷ All current guidelines discourage opioid use for fibromyalgia. Opioid use in this population can actually cause worsening of fibromyalgia, causing greater pain sensitivity or making pain persist.²

There are currently three FDA-approved medications for the treatment of fibromyalgia: dulox- etine, milnacipran, and pregabalin (Table 7.2).¹²⁸ While not completely understood, the effect of duloxetine and milnacipran on chronic widespread pain is thought to be due to direct alteration of serotonin and norepinephrine reuptake at the level of the dorsal horn in the descending pain pathways.¹²⁹ Amitriptyline and cyclobenzaprine also have effects on serotonin and norepinephrine and can be used to treat the symptoms of fibromyalgia, but are not FDA-approved. In addition to

TABLE 7.2

Prescription Medications Commonly Used for Fibromyalgia

*FDA-approved; GABA, gamma-aminobutyric acid; SNRI, serotonin-norepinephrine reuptake inhibitor.

pregabalin, which is involved in pain transmission by binding to voltage-gated calcium channels in several areas of the central nervous system and spinal cord, gabapentin can also be used.² Tramadol is a weak opioid analgesic with mild serotonin-norepinephrine reuptake inhibitor (SNRI) effects. Benefits seen with tramadol for fibromyalgia are likely due to its SNRI effects over opioid effects.

To help manage sleep issues associated with fibromyalgia, many of the medications that are used for the treatment of symptoms of pain also have side effects that can promote sleep.²

Because fibromyalgia is a heterogeneous disease, medication therapies offer mixed results in terms of efficacy for individual patients. It has been estimated that approximately half of all treated patients experience a 30% reduction in their symptoms with medication therapy.¹³⁰

Additionally, this patient population is often more sensitive to medications and has a higher incidence of adverse effects. Doses are typically low'er when used for fibromyalgia as compared to other disease states (Table 7.2). For this reason, and in the context of the opioid crisis, it is important to continue research on practical pharmacotherapy options for fibromyalgia.

Medications and Experimental Agents under Study for Fibromyalgia

Low-Dose Naltrexone

It has been proposed that fibromyalgia may represent a state of hypersensitive microglial activity and increased inflammation in the CNS.¹³¹ Known to suppress microglial activity, naltrexone, at doses approximately one-tenth the typical opioid addiction dose, could be a potential treatment for fibromyalgia.¹³² Low-dose naltrexone (LDN) exhibits paradoxical properties of analgesia and anti-inflammatory actions that are not seen with higher doses. By suppressing release of proinflam- matory factors and antagonizing microglial activity, LDN may reduce pain and other symptoms of fibromyalgia.

In a single blind, cross-over pilot study of ten women with fibromyalgia, LDN (4.5 mg daily) was found to reduce fibromyalgia symptoms for all study patients with a >30% improvement over placebo as measured by daily reports of symptom severity and tests. Twice-monthly tests of mechanical, heat, and cold pain sensitivity demonstrated that mechanical and heat pain thresholds were improved with the drug. Patients with higher erythrocyte sedimentation rates had the greatest reduction in symptoms with LDN. Side effects were rare (including insomnia and vivid dreams) and short-lived. Although this study had promising results, it is important to note that there were several constraints. This study was single blind, included only a small number of patients, was not counterbalanced, and had a short duration of treatment (LDN was administered for 8 weeks).¹³³

In a larger randomized, double-blind, placebo-controlled, crossover study, LDN was administered at a dose of 4.5 mg daily for a period of 12 weeks with 4 weeks of placebo taken either before or after the LDN treatment period depending on study arm assignment. This study also included a 2-week baseline period and a 4-week follow-up period for a total length of 22 weeks. All participants were told that they had the option to reduce their daily dosage to 3.0 mg if they experienced side effects. Each participant was given a handheld computer to record their pain, fatigue, and other symptoms on a daily basis, and they continued to record their symptoms for 4 weeks after study medication was stopped. Thirty-one women were enrolled and 28 women had sufficient data to be included in the analyses. Study patients experienced a significantly greater reduction in their pain scores while they were taking the LDN as compared with placebo (28.8% reduction versus 18.0% reduction; p=0.016). More participants met criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during LDN therapy compared to placebo (32% response during LDN versus 11% response during placebo; p=0.05). They also reported improved general satisfaction with life and improved mood while taking LDN. However, there was no improvement in fatigue or sleep. All participants tolerated the LDN, with few side effects. Four individuals (three while taking LDN and one while taking placebo) requested the 3.0-mg dosage due to side effects. Side effects resulting in a dose decrease were headaches, heartburn, and irritability. These side effects were reduced by lowering the dosage to 3 mg/day. Low-dose naltrexone may be a great treatment strategy due to its high bioavailability, long history of safe use, low cost, and accessibility.¹³⁴