Fibromyalgia is a chronic disorder that manifests as widespread concentration difficulties, fatigue, headaches, mood changes, pain, sleep disruption,1-3 and tenderness.

Patients may also have anxiety, depression, functional impairment of daily activities, and other unexplained symptoms. Emotional distress, endocrine disorders, immune activation, and physical trauma have the potential to trigger fibromyalgia. Women are affected more often than men, and fibromyalgia generally presents in middle-aged or young patients.4,5 Its prevalence in the United States has been estimated at about 2%, but thought leaders indicate that this figure is low.6

UNKNOWN CAUSES
Although the exact causes of fibromyalgia are unknown, experts suspect a combination of environmental and genetic factors. Researchers indicate that the condition may emanate from 2 mechanisms that affect the central nervous system (CNS): CNS hyperreactivity and a decreased pain modulation capacity in the CNS, probably associated with decreased activity of serotonergic/noradrenergic pathways.5,7 Patients with fibromyalgia may have lower cerebrospinal fluid levels of noradrenaline metabolites and lower levels of 5-hydroxyindoleacetic acid, serum serotonin, and tryptophan than people who do not have fibromyalgia. They may also have higher levels of nerve growth factor, pronociceptive (pain sensing) neurotransmitters, and substance P. Additionally, patients tend to have functionally impaired and lower-density small nerve fibers.8 Researchers are also looking at other possible causes or contributing factors, such as aberrant sleep architecture, abnormal autonomic nervous system functioning, dysfunctional dopaminergic neurotransmission, catechol-O-methyltransferase gene polymorphisms, and hypothalamic–pituitary–adrenal axis changes. Psychological and physical factors also seem to affect each patient’s fibromyalgia presentation.9

The overall approach to treating fibromyalgia is described in the figure.10,11 A main strategy in treating fibromyalgia is to use interventions to limit peripheral input that increases allodynia, hyperal gesia, and pain. Further, it is important to address sources of comorbid pain.12 The table13 lists the categories of medications used most often, and pharmacists should note that they are typically used in combination. As patients often cannot tolerate recommended doses, the principle of “start low, go slow” needs to be applied.





Many patients with fibromyalgia experience depression. Treating depression will not cure fibromyalgia but it may improve patients’ sleep and reduce pain.14 The FDA has approved 3 drugs specifically for fibromyalgia: the antidepressants duloxetine and milnacipran to relieve fatigue, pain, and sleep problems, and pregabalin to improve sleep and reduce pain.15

Clinicians often employ gabapentin and pregabalin to enhance health-related quality of life, improve sleep, and treat chronic pain. Although the tricyclic antidepressants have fallen out of use for many conditions, amitriptyline has remained a useful adjunct in fibromyalgia, especially in combination with fluoxetine or pregabalin, plus duloxetine.10,11 Low-dose amitriptyline, cyclobenzaprine, and pregabalin, administered at bedtime, are also used to address sleep disturbances.11 Guidelines also recommend tramadol, administered alone or together with acetaminophen, as studies indicate that it reduces pain by 30%.13 

SEEKING BETTER OPTIONS
Unfortunately, many patients are intolerant of or unresponsive to these drugs, indicating an unmet need for better, targeted medications. Researchers are investigating IMC-1, which is a fixed-dose combination of famciclovir, an antiviral nucleoside analog, and celecoxib, a COX-2 inhibitor with unique antiviral activity. The FDA gave this product a fast track designation based on phase 2 study results.16,17 The theory behind this combination is that herpes viruses seem to upregulate COX-2 enzymes, and many patients with fibromyalgia may be unable to suppress the virus adequately.16 Other agents under study include neurotrophins, mast cell stabilizers, and mirogabalin, a more specific cousin of gabapentin or pregabalin.13

Patients with fibromyalgia often receive potent opioid analgesics from clinicians who are inexperienced in treating this condition. Opioids have limited efficacy in most of these patients and are generally not recommended, except for those with severe allodynia who failed to respond to other approaches. If patients are taking high doses of opioids, clinicians should gradually withdraw opioids under close medical supervision.18

COUNSELING
Many patients with fibromyalgia have cognitive limitations and may process verbal information poorly. Providing understandable written instructions describing medications and schedules is the best way to ensure adherence. Clinicians should instruct patients to ask about OTC medications or supplements before using them. Often, patients with this disorder experience symptoms that wane and wax, so identifying and avoiding triggers is important. A key intervention is exercising moderately and pacing one’s activity to match energy levels.19

In addition, as they are likely to take several if not many drugs, patients will need help identifying ways to ensure adherence to medication.

CONCLUSION
Many options are available to treat fibromyalgia, but no single option is effective for its symptom constellation. Treatment is a balancing act and requires considerable trial and error. A final reminder is important: Avoid anxiolytics, hypnotics, opioids, and skeletal muscle relaxants that have abuse potential or may worsen cognitive dysfunction and fatigue.
 
Jeanette Y. Wick, RPh, MBA, FASCP, is the assistant director of the Office of Pharmacy Professional Development at the University of Connecticut School of Pharmacy in Storrs.

REFERENCES
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