A variety of pharmacologic and non-pharmacologic inter- ventions are utilized in FMS treatment. Most practitioners agree that both medications and physical modalities are essential to any well-formulated treatment plan. Many stud- ies of FMS treatments are limited by small sample size, short duration, and lack of blinding and randomization.
There have been no randomized controlled clinical trials
that focus specifically on FMS in older adults. Table 6.4 lists common medications for FMS treatment.
Antidepressants
Antidepressant medications, including the tricyclic antide- pressants (TCAs), the selective serotonin reuptake inhibitors
Table 6.4 Medications for the treatment of FMS in older adults
Drug Recommended starting dose and titration Comments
Anticonvulsants
Gabapentin 100–1,200 mg daily in divided doses.
Starting dose; 100 mg nightly. Increase by 100 mg weekly.
Renal dosing: CLcr 30–59 mg/min, titrate to 600 mg bid.
CLcr 15–29 mg/min, titrate to 300 mg bid.
CLcr < 15 mg/min, titrate to 300 mg qd.
Supplemental dosing after dialysis.
May cause sedation dizziness, peripheral edema, weight gain.
Adjust dose for renal insufficiency as determined by the Cockroft–Gault equation: Creatinine Clearance = (140-age) × (Weight in kg) × (0.85 if female)/(72 × Cr)
Pregabalin Initiate at 25–50 mg nightly. Increase by 25–50 mg weekly up to 100 mg BID. Max dose 300 mg QD.
Renal dosing: CLcr 30–60 mg/min adjust dose to 150–300 mg QD. CLcr 15–30 mg/min adjust dose to 75–150 mg QD. CLcr < 15 mg/min adjust dose to 25–50 QD.
Supplement dose after dialysis.
FDA approved for fibromyalgia.
Side effect profile similar to gabapentin.
Adjust dose for renal insufficiency as determined by Cockroft–Gault equation (see above).
Tricyclic antidepressants
Nortriptyline 10–50 mg nightly.
Initiate at 10 mg nightly and increase by 10 mg every week as needed.
Amitriptyline is contraindicated in older adults.
All tricyclic antidepressants have some anticholinergic potential, e.g., sedation, delirium, constipation. Avoid in narrow angle glaucoma and in presence of QT prolonga- tion. Recommend baseline EKG to evaluate Q–T interval, then periodically with titration. If QT prolongation develops, taper off.
Serotonin reuptake inhibitors (SSRI)
Fluoxetine 20–40 mg daily. Initiate at 10 daily. Increase by 10 mg after 1 month.
SSRIs may have superior tolerability compared to TCAs.
Because of its very long half life, fluoxetine is not recommended as first line treatment for older adults.
Citalopram 20–40 mg daily. Initiate at 10 daily for 7 days.
Increase to 20 mg if tolerated.
Serotonin norepinephrine reuptake inhibitors (SNRIs)
Venlafaxine 150 mg daily. Initial dose of 37.5 mg daily. Increase by 37.5 mg weekly as tolerated.
Avoid in those with uncontrolled hypertension.
Duloxetine 60 mg daily. Initiate at 30 mg daily. May increase to 60 mg after 1 week.
FDA approved for fibromyalgia. Avoid in patients with liver disease and narrow angle glaucoma.
Milnacipran Administer in two divided doses per day. Begin dosing at 12.5 mg on the first day and increase to 100 mg/day over a 1-week period. May be increased to 200 mg/
day based on individual patient response.
FDA approved for fibromyalgia. Compared to duloxetine and venlafaxine, has a higher affinity for inhibition of norepinephrine reuptake than serotonin reuptake in vitro.
Blood pressure and heart rate should be monitored.
For all SNRI medications, dose should be adjusted in patients with severe renal impairment.
Analgesics
Tramadol Start at 25 mg qd; increase 25–50 mg qd in divided doses q 3–7 days to maximum of 100 mg qd.
If Clcr < 30, reduce to 50–100 mg bid.
May cause sedation and confusion. Avoid in patients with seizures. May cause serotonin syndrome in combination with other serotonergic agents. Adjust dose for renal insufficiency as determined by the Cockroft–Gault equation (see above).
Muscles relaxants
Cyclobenzaprine 5–10 mg nightly Likely to cause sedation. Similar side effects to tricyclic antidepressants.
(SSRIs), and the serotonin norepinephrine reuptake inhibitors (SNRIs) are the most widely studied drugs for FMS treat- ment. In general, these medications increase central ner- vous system levels of serotonin and norephinephrine that result in enhanced descending inhibition. In addition to reducing FMS pain, antidepressant medications may improve sleep and reduce fatigue independent of any effect on depression [58–60].
The class of medications that has been most widely stud- ied is the tricyclic antidepressants (TCAs). These medica- tions inhibit reuptake of both serotonin and norepinephrine in addition to blocking sodium channels [61, 62]. Low doses of amitriptyline (25–50 mg) taken at night have been demonstrated to improve sleep and morning stiffness in FMS patients [63, 64]. Cyclobenzaprine, a tricyclic that is Food and Drug Administration (FDA)-approved as a mus- cle relaxant, also provides analgesia [65]. Side effects of TCAs and cyclobenzaprine include sedation, confusion, constipation, and palpitations. These side effects may be severe, and a large percentage of patients are unable to tol- erate TCAs. Prolongation of the QT interval, which in the worst-case scenario results in torsade de points and death, has also been reported with TCAs. Experts agree that ami- triptyline is contraindicated in older adults [66, 67].
Nortriptyline and desipramine have fewer side effects and are potential choices at doses of 10–25 mg nightly. We rec- ommend obtaining an EKG prior to use in patients who are 50 years and older and avoiding TCAs in patients with car- diac abnormalities, especially disorders of the cardiac con- duction system.
Both the selective serotonin reuptake inhibitors (SSRIs) and the dual reuptake inhibitors (SNRIs) are important in FMS treatment. These drugs have fewer side effects com- pared to TCAs. Fluoxetine and citalopram, two drugs in the SSRI class, have shown some success in treating FMS symp- toms compared to placebo [68–70]. Although fluoxetine is the only antidepressant that has FDA-approval for the treat- ment of major depressive disorder in late life, we do not advocate its routine use in older adults because of its very long half life.
The SNRIs appear to have more promise for the treatment of FMS in older adults. Duloxetine is safe and effective at doses up to 120 mg/day [71–73]. Recent double blind-pla- cebo controlled trials of duloxetine demonstrated improve- ment in FMS pain [59, 74]. Duloxetine is now the second FDA approved medication for FMS treatment. Milnacipran is the other SNRI that is approved by the FDA for the treat- ment of fibromyalgia. It has been shown to reduce pain and fatigue, improve overall well-being [75], and improve dys- cognition [76].
Venlafaxine is not as well-studied as duloxetine for the treatment of FMS, but evidence indicates that it reduces pain, fatigue, and morning stiffness at doses ranging
between 75 and 375 mg daily [77, 78]. It acts as a SSRI until the dosage is increased to >150 mg/day at which point it begins to inhibit the reuptake of norepinephrine. Some older adults may not be able to tolerate these safe but rela- tively elevated doses.
Anticonvulsants
Both gabapentin and pregabalin are used for FMS treatment.
Pregabalin, the first FDA-approved medication for FMS, decreases pain and improves function at doses between 300 and 450 mg daily [79]. Gabapentin is not FDA approved for FMS but was effective compared to placebo in a 12-week, randomized, double-blind study. Pain scores were signifi- cantly reduced with gabapentin doses between 1,200 and 2,400 mg daily [80]. While the exact mechanism of action of these drugs is unknown, they are believed to decrease central sensitization. Dizziness and drowsiness are often encoun- tered early in treatment and may cause falls-related morbid- ity and mortality. Weight gain and peripheral edema are additional concerns with pregabalin and gabapentin. Initiating at low doses with slow upward titration may reduce side effects. Our target dose of gabapentin for older adults with FMS is generally between 300 and 1,200 mg/day, although some patients may respond to as little as 100 mg at bedtime.
When we prescribe gabapentin to older adults, we typically start at 100 mg/night and increase the dose by 100 mg every week. While this titration schedule is very conservative, our clinical experience has taught us that many side effects of gabapentin (daytime sedation, dizziness) can be avoided with these incremental increases. Similarly, our titration schedule for pregabalin is to start at 25–50 mg/night and increase the dose by 50 mg increments every week to a target dose of 150–300 mg/day.
Analgesics
Opioid analgesics are poor initial choices for FMS patients.
Recent evidence suggests that FMS patients bind opioids weakly [81]. This may be one factor in limiting their effec- tiveness. For some patients, however, opioids are necessary to obtain analgesia. If opioids appear to be the only solution, we recommend further assessment of anxiety and depres- sion, as the opioids may actually be treating these associated conditions (as opposed to the pain of FMS). Adverse effects of opioid treatment in older adults include dysmobility and falls, delirium, depression, sedation, nausea, and vomiting.
A pain specialist’s evaluation may be helpful if prolonged treatment with opioids is anticipated.
53 6 Widespread Pain in Older Adults
Tramadol, a mu receptor agonist with dual serotonin and norepinephrine reuptake inhibition may be an effective anal- gesic for patients with FMS [82]. As with other opioids, pro- longed use of tramadol may be linked to abuse and dependence, and should be considered judiciously. Other concerns when prescribing tramadol in older adults include a risk of serotonin syndrome when co-prescribed with an anti- depressant, and a lowered seizure threshold. Tramadol is often formulated with acetaminophen (Ultracet). Prescribers need to be cognizant of any other products containing acet- aminophen to avoid the risk of liver injury. For patients older than 75 years, the recommended daily dose of acetamino- phen is 3,000 mg.
Treatment of Comorbid Psychiatric Disorders
First line treatment of anxiety disorders such as generalized anxiety disorder and panic disorder is with an antidepressant.
Anxious patients with chronic widespread pain are often exquisitely sensitive to medication side effects and hypervigi- lant for unfamiliar bodily sensations. When utilizing an anti- depressant in these patients, we often begin at half the recommended starting dose for several days, and incremen- tally increase the dose of the medication to a therapeutic level.
Providing education about side effects so patients are not
“taken by surprise” often improves compliance and reduces early medication discontinuation. Discussions with depressed or anxious patients with chronic widespread pain often include a variation of the following: “This medication is an antidepres- sant that should help your pain, mood, and anxiety. Sometimes people experience an upset stomach, headaches, increased anxiety, and sweating. We’ll start this medication at a low dose and increase it slowly to avoid these annoying but not danger- ous side effects. If you can stick with taking the medication every day and let me help you manage any of these side effects that should go away by themselves in less than a week, there is a good chance that this medication may help you.”
Some older patients with chronic widespread pain have such high levels of anxiety and are so intolerant of medica- tion side effects that they will benefit from a low dose of a benzodiazepine during the initiation of treatment. There is always a risk-benefit analysis that must occur before pre- scribing a medication that has the potential to impair cogni- tion or increase the risk of falls in older adults such as benzodiazepines or opioid analgesics. In general, if acute anti-anxiety medication is required for short-term treatment as antidepressant pharmacotherapy is initiated, we use lora- zepam at doses of 0.5 mg one to two times a day. Management of comorbid anxiety often reduces the severity of chronic widespread pain and can reduce the number and amount of other medications used to manage the pain condition.
The other conditions associated with psychological functioning and for which there are treatments are fatigue and insomnia. Both fatigue and non-restorative sleep are associated with worsened cognitive functioning, decreased quality of life, and increased morbidity in older adults [83].
Behavioral treatments that enhance sleep hygiene such as:
Reduction of stimulants or alcohol in the afternoon and
•
evening
Maintaining a regular good night and good morning time
•
Restricting the bed for sleep and sex
•
Encouraging regular exercise
•
Scheduling one short nap and/or minimizing other day-
•
time sleepingshould be the first line recommendations.
Treatment of insomnia includes the use of sedating antide- pressants such as low dose trazodone or mirtazapine. If fatigue and daytime sedation do not improve with pain management, treatment of depression, and discontinuation of any unnecessary sedating medications (e.g., diphenhy- dramine, clonazepam), then treatment with a stimulant such as methylphenidate or modafinil can usually be safely used in most older adults with excessive daytime fatigue.
Non-pharmacological Management
Strong efficacy evidence exists for aerobic exercise and cognitive-behavioral therapy (CBT) interventions that should be considered first line treatments for FMS [84].
These non-pharmacologic approaches are particularly attrac- tive for older adults, to avoid the risk of polypharmacy and adverse drug reactions. An optimal treatment program com- bines educational sessions, exercise and stretching, and CBT. The benefits of regular exercise include enhanced physical and cardiovascular fitness, improved activity toler- ance, heightened mood and endorphin levels, and decreased pain [85, 86]. FMS patients often present with baseline deconditoning; however, with the assistance of skilled phys- ical therapists, paced exercise may be introduced at a well- tolerated level. Occupational therapists can teach patients energy- conserving movements and behaviors that may improve endurance and reduce pain. During pain flares, daily aerobic programs should be modified but not stopped.
Water therapy is an excellent option for patients with arthritic conditions who have difficulty with weight bearing.
In addition to physical activity, education and CBT are effective in FMS management. Through educational sessions patients come to understand FMS as a manageable condition rather than a progressive and disabling disease. CBT improves active coping, problem solving, and cognitive distortions, and reduces pain behavior and symptom magnification.
Relaxation techniques that improve sleep may be especially valuable for those with comorbid depression and anxiety.
Acupuncture also may be helpful for the treatment of FMS. Several randomized controlled trials of acupuncture have shown effectiveness for relieving FMS symptoms although none have been performed exclusively in older adults [87, 88]. These data are encouraging given the overall safety of this treatment modality. At this point there is weak evidence to support other non medical options including chi- ropractic manipulations, massage therapy, interferential cur- rent, ultrasound, and trigger point injections [84].
Conclusion
Widespread pain is common in older adults and its differen- tial diagnosis is broad. Fibromyalgia syndrome commonly is responsible and diagnosis relies entirely on a careful history and physical examination. A number of pharmaco- logical and non-pharmacological treatments have strong efficacy evidence. While none have been studied exclu- sively in older adults, our clinical experience indicates that these patients often do very well with both pharmacological and non-pharmacological treatments.
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