Medications for poor sleep (insomnia and nonrestorative sleep)
Disordered sleep has been implicated in the pathogenesis of FMS.16 Patients who have FMS should be evaluated for sleep disorders, and psychological and behavioral treatments should be tried before therapy with medications is considered.
Pregabalin, 25 to 225 mg taken at night, is recommended as first-line treatment for patients who have FMS with poor sleep because this agent can improve sleep and other FMS symptoms.17 Benzodiazepines are not recommended because they may have detrimental effects on sleep architecture and cognition and they have addiction potential.
Ramelteon, a melatonin(Drug information on melatonin) receptor agonist taken as an 8-mg tablet 90 minutes before bedtime, usually is well tolerated. However, it may take 30 days to show effectiveness. Eszopiclone, a nonbenzodiazepine hypnotic taken as a 1-, 2-, or 3-mg tablet immediately before bedtime, has rapid effectiveness, but headache and an unpleasant taste can limit tolerability. Caution should be taken in combining ramelteon and eszopiclone with other sedatives, and patients should be monitored for worsening depression or suicidal ideation.
Sedating antidepressants may be beneficial for depressed patients who have FMS with insomnia. TCAs have long been used to manage nighttime pain and insomnia (5 to 30 mg of cyclobenzaprine(Drug information on cyclobenzaprine) or 10 to 50 mg of amitriptyline(Drug information on amitriptyline)). Mirtazapine(Drug information on mirtazapine), 15 to 30 mg taken at night, can improve symptoms of pain, insomnia, fatigue, and depression in patients with FMS.18 Because mirtazapine somnolence is inversely proportional to dose, the dose should be increased in patients with excessive morning sedation.
Trazodone is highly sedating and best suited for patients who are refractory to other sleep medicines. In a recent open-label study of patients with FMS, trazodone monotherapy given at bedtime at an average dose of 200 mg significantly improved sleep quality along with global FMS severity and depression.19 In the same study, the subsequent addition of pregabalin(Drug information on pregabalin) to trazodone monotherapy at an average dosage of 325 mg/d led to further significant improvements in global FMS severity and depression as well as decreases in bodily pain and pain interference with activities of daily living. The adverse effects seen most frequently during the combination period, including light-headedness, dizziness, and edema, were typical of those seen with pregabalin monotherapy.
Many patients with FMS sleep well but awaken feeling unrefreshed; they require medications that improve sleep quality rather than quantity.16 Pregabalin is recommended as first-line therapy for nonrestorative sleep because it improves sleep architecture at FMS-indicated doses.17 Chlorpromazine(Drug information on chlorpromazine), 100 mg taken at bedtime, has been shown to increase slow wave sleep and improve pain and mood in patients with FMS,20 but poor tolerability limits use in most patients. Quetiapine(Drug information on quetiapine), 25 mg taken at bedtime, can improve sleep quality and other FMS symptoms,21 but tolerability is poor. Trazodone, 100 mg taken at night, improved sleep architecture in patients with somatoform pain disorder.22
Sodium oxybate, 3 mg taken at bedtime and again 4 hours later, improved sleep quality and other FMS symptoms.23 However, sodium oxybate is highly sedating and patients should have sleep testing to rule out apnea before using it. Also, because sodium oxybate has a high cost and abuse potential, it is not an option for most patients with FMS.
Managing depression and anxiety with antidepressants
One-third of patients who have FMS also have severe depression or anxiety that can hamper disease management and increase the risk of suicide.24 Therefore, management of mood disorders is vital.
Because duloxetine(Drug information on duloxetine) is FDA- approved for depression and anxiety at FMS-indicated doses, this agent is recommended as first-line therapy for patients with FMS who have mood symptoms. Venlafaxine is a generic SNRI alternative that is effective in FMS management for patients who cannot afford duloxetine.25
Milnacipran is used as an antidepressant in Europe and Japan, but monotherapy often is not sufficient to manage depression in patients with FMS and it can worsen anxiety. With the addition of a small dose of a generic SSRI to milnacipran therapy, depression and anxiety symptoms often can be managed at minimal cost with good tolerability. However, patients should be monitored for development of serotonin toxicity.9
Managing stiffness with muscle relaxants
Stiffness is problematic for most patients with FMS,1 and management is important for maintaining functionality and allowing for participation in exercise. Although daily stretching is useful for managing stiffness in all patients with FMS, muscle relaxants may be helpful adjuncts for those who have persistent stiffness.
A thorough review of the risks and benefits of muscle relaxant use is available.26 Here the focus is on the use of muscle relaxants in FMS management.
Cyclobenzaprine can improve FMS stiffness as well as pain, sleep, tenderness, and global function.27 This agent also may be helpful during FMS "flares." However, many patients cannot take cyclobenzaprine during the day because of sedation.
Amrix, an extended-release form of cyclobenzaprine, may be taken at bedtime to improve daytime tolerability. Methocarbamol(Drug information on methocarbamol) and metaxalone, less sedating muscle relaxants, may be used in those patients who do not tolerate cyclobenzaprine.
Antispasmotics, such as baclofen, can reduce stiffness and manage muscle spasms, which are common in patients with FMS. Tramadol(Drug information on tramadol) also can improve FMS stiffness.
Analgesic medications to manage FMS pain
Patients with FMS often experience pain flares that necessitate short-term analgesic therapy. Although acetaminophen is a common adjunct for FMS pain, the effective dosage usually is at the recommended maximum of 3000 mg/d and patients often are nonadherent to the necessary frequency of administration.
NSAIDs have similar analgesic effects, but efficacy in FMS management is lacking and NSAIDs are not recommended for patients with primary FMS.2 Although patients with FMS and concomitant inflammatory conditions or osteoarthritis may benefit from NSAID therapy—because such "pain generators" can worsen all FMS pain—NSAIDs combined with serotonin-active medications may increase the risk of bleeding and caution is advised in patients who are receiving antiplatelet or anticoagulant drugs or are at risk for GI bleeding.
Tramadol is the only narcotic medication recommended for managing FMS because it also has SNRI activity.2 One or 2 tramadol/acetaminophen 37.5/325-mg tablets taken 4 times daily can significantly improve pain, stiffness, and work interference in patients with FMS.28
Tapentadol, a narcotic that also has norepinephrine(Drug information on norepinephrine) reuptake inhibition, currently is FDA-indicated only for relief of acute pain. Trials are needed to determine whether this agent could be beneficial in managing FMS.
Traditional narcotics should be avoided for FMS management because their effectiveness is poor and discontinuation may be difficult because of the development of rebound pain. Patients with FMS should be screened for a history of drug abuse before they receive narcotics, because abuse history is predictive of future abuse.
Effective FMS management requires an individualized treatment approach that addresses all problematic symptoms. Monotherapy usually is not sufficient to manage the myriad problems experienced by most patients with FMS. Although combination pharmacotherapy is a useful approach that can improve FMS management for many patients, such therapy must be given cautiously because it carries increased risks.
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