What other medications have shown effectiveness in therapy for Fibromyalgia

What other medications have shown effectiveness in therapy for Fibromyalgia?

Patients often cannot afford or insurance may deny the use of FDA-approved medications to treat FM. Several other medications can be used.

  • 1. SNRI: Venlaxafine (Effexor) is an SNRI shown to be beneficial in FM. It could be used in someone who cannot afford duloxetine or milnacipran which are also SNRIs. Venlaxafine is often started at 37.5 mg in the morning with food and increased weekly to effect or max dose of 375 mg daily (typical dosing: 75–150 mg BID). There is an extended release form that can be used once a day starting at 37.5 mg and titrated weekly to effect or max dose of 225 mg daily.
  • 2. TCAs: Low-dose TCAs administered before bedtime have been objectively demonstrated to improve the sleep disturbance, pain, and tender points in a proportion of patients with FM. An example of such a regimen is the administration of amitriptyline at a dosage of 10 to 25 mg 1 to 3 hours prior to bedtime. This dose may be increased by 10 to 25 mg increments at 2-week intervals; the usual effective dose is 25 to 100 mg daily. Adverse effects are common and are due to the TCA’s anticholinergic and antihistamine activities. They include morning drowsiness, dry mouth, and constipation. If amitriptyline causes too many side effects, other TCAs can be tried.

Sedative
Anticholinergic
Amitriptyline (Elavil, Endep)++++++++
Imipramine (Tofranil)++++++
Doxepin (Sinequan)++++++
Nortriptyline (Pamelor)+++
Desipramine (Norpramin)++

As shown, the secondary amines (nortriptyline, desipramine) may be better tolerated but are less strong than the tertiary amines. In addition, amitriptyline and imipramine are most likely to cause orthostatic hypotension and cardiac toxicity (arrhythmias), although others may also cause these problems. Cyclobenzaprine (Flexeril) also acts as a weak TCA-like drug in FM. It is commonly used to treat muscular stiffness, and low-dose therapy has been studied as an augment to sleep disturbance as well. Dosing typically starts at 5 to 10 mg at bedtime (QHS). Daytime dosing may be added. Maximum daily dose is 30 mg.

Although the mechanism of action of TCAs in FM treatment remains unclear, the small dosages used and the rapid onset of action suggest that it is not due to the treatment of underlying depression. Since TCAs inhibit the reuptake of serotonin (and norepinephrine) at synaptic junctions, it is hypothesized that the greater availability of serotonin may be responsible for improved stage IV sleep in addition to providing a central analgesic effect through potentiation of the descending analgesic pathways. TCAs may also have an effect on CNS endorphins as well as on peripheral pain receptors.

  • 3. Anticonvulsants: Gabapentin (Neurontin) can be used as a less expensive substitute for pregabalin. Dosing is often started low due to the fact that patients with FM often experience general drug intolerance. A common approach would start at 100 to 300 mg QHS. If 300 mg QHS is tolerated, a morning dose can be added and titrated to effect. Typical dosing: 300 to 600 mg thrice a day (TID; maximum dose 1200 mg TID).
  • 4. Analgesia. Tramadol (Ultram) has been shown to help pain in patients with FM. The analgesic effect of tramadol is most likely due to its SNRI effect and not due to its weak binding to the mu opioid receptor. In fact opioids are not effective in FM and should be avoided. Likewise acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs) are not effective for analgesia unless the patient also has associated pain due to osteoarthritis. Trigger point injections with lidocaine +/– corticosteroid should be used sparingly and only in patients with a myofascial trigger point (and not in tender points; see Question 2) unresponsive to physical therapy.
  • 5. Other “niche” therapies: Other medications have been tried depending on the associated symptoms:
    • – Selective serotonin reuptake inhibitors (SSRIs): may be used to treat associated depression.
    • – Modafinil (Provigil): has been described in noncontrolled, retrospective series to treat fatigue. Dose varies between 50 to 200 mg BID. Armodafinil (Nuvigil) can also be used.
    • – Trazodone (Desyrel): may help sleep disturbances. Start 25 mg QHS and titrate weekly to effect. Maximum dose is 200 mg QHS.
    • – Ropinirole (Requip): a dopamine (D3) receptor agonist that can help restless leg syndrome. Start 0.25 mg 1 to 3 hours before bed and titrate to effect or max dose 4 mg QHS.
    • – Naltrexone: trials have shown that low-dose naltrexone (4.5 mg daily) improves pain and mood in 30% of FM patients. It does not improve fatigue or sleep. The mechanism of action is unclear but is postulated to be due to the ability of low-dose naltrexone to attenuate the production of proinflammatory cytokines and neurotoxic superoxides via suppressive effects on CNS microglia cells. Low doses do not affect the mu opioid receptors.
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