Post by Lady~RavenHeart on Nov 8, 2005 22:13:31 GMT 2
Amitriptyline seems to be one of the more commonly used medications (especially in South Africa it seems) in the treatment of FMS and associated sleeplessness.
There are, however, a host of other medications that are available. Find the one that works for you and stick with it as long as it works.
Treatment of CFS and FMS
Since the etiologies of CFS and FMS are so vague, there currently is no consensus on how the outcomes to clinical interventions should be measured. There are many different aspects of CFS and FMS that researchers are studying. As a result, these studies are conducted using varying methods to measure different outcomes, with the tools used to measure the outcomes also differing. This makes reproducing study results, and comparing the results of various studies, difficult. As more is understood about the etiologies of CFS and FMS, and consensus is reached on how to conduct research studies and measure specific outcomes, the treatment of CFS and FMS will become better defined. (9)
The goal of CFS and FMS therapies is to improve patient symptoms. Specifically, the objectives of treatment should be to: 1) improve pain control and improve the quality of sleep, 2) minimize fatigue to enhance or maintain patient functionality at work and/or at home, and 3) minimize the suffering and distress often observed in FMS patients. (9, 13, 17)
The approaches to treating CFS and FMS are very similar, since the syndromes have many overlapping characteristics. A short review of the role of some endogenous substances thought to play a role in CFS and FMS will be helpful in understanding the rationales behind some of the therapies.
Serotonin (S): S is needed for sleep regulation and induction of Stage 4 sleep. Eight different S receptors are known to date, explaining why some S altering therapies work, and others do not. S is also involved in pain regulation. It is involved in setting the sensory pain threshold in the thalamus, with a deficiency resulting in lowered pain threshold. Some references claim S is a pain inhibitor. S impacts immune function, and the vasomotor and temperature control centers in the brain. Low levels of serotonin in the CNS are associated with depression. (3, 4, 12, 13, 17)
Norepinephrine (N): N is a major neurotransmitter involved with regulating the ANS. It also is needed for sleep regulation, and to induce Stage 4 sleep. N is active in pain regulation and thought to inhibit pain sensation. Its role in immune function is under study. (4, 13, 17)
Dopamine (D): Low brain levels of D may contribute to sleep arousal conditions, such as restless leg syndrome (RLS) and periodic limb movements during sleep (PLMS). Both of these conditions are reported in CFS and FMS patients. (17)
GABA (G): G slows down CNS nerve impulses that may interfere with sleep. (17)
Interleukin-1 (IL-1): IL-1 is an immune system cytokine that is essential to promoting sleep. (17)
Pharmacological Treatments
In general, FMS patients take an average of 3 of the following medications: NSAID - 33% of patients, antidepressant - 69% of patients, muscle relaxant - 13% of patients, benzodiazepine - 15% of patients, occasional narcotic analgesic - 37% of patients. (8) The medications prescribed to treat CFS and FMS typically are not officially indicated for this use. Below is a summary of medications commonly used to treat CFS and FMS, the drug dosages most often used in CFS and FMS patients, the side effects most often reported by these patients, and counseling points that may be helpful. References 2, 3, 5, 9, 12 and 17 provide a more comprehensive discussion of CFS and FMS pharmacological therapies. See Reference 18 for detailed dispensing information for each of the medications discussed.
Tricyclic Antidepressants (TCAs) (1, 4, 8, 13, 17, 18)
· Amitriptyline (Elavil, Endep) 5 mg - 25 mg HS
· Cyclobenzaprine (Flexeril) 5 mg - 40 mg HS
· Doxepin (Sinequan, Adapin) 1 mg - 25 mg HS
· Trazodone (Desyrel) 50 mg - 150 mg HS
TCAs increase brain serotonin and/or norepinephrine levels, and block histamine and/or acetylcholine to varying degrees. For a detailed comparison of these medications, see references 17 and 18. Research on TCAs evaluates their impact on the amount of time spent in quality deep sleep, the number of arousal disturbances during sleep, and the overall impact on patient symptoms. Although the results of the studies are not definitive, several controlled studies showed that TCAs reduce symptoms in a significant number of patients. TCAs are contraindicated in patients that experience PLMS because they can make patients feel worse. They are also contraindicated in patients receiving MAO inhibitor therapy within 14 days, and in narrow-angle glaucoma. Caution is recommended in patients having a seizure history, urinary retention, cardiac problems, psychiatric conditions, and patients that are hyperthyroid or taking thyroid medication.
Amitriptyline is the most commonly prescribed TCA. It benefits about 25% of FMS patients in the areas of pain, stiffness, fatigue, and sleep disturbances. It seems less effective in patients having FMS symptoms for more than 5 years. Therapy should be initiated at the lowest dose possible, preferably on the last day of the work week (Friday for most people). If drug hangover is a problem, take the dose earlier in the evening, rather than before bedtime. It takes up to 1 month to experience maximum therapeutic benefits. Amitriptyline is the TCA that has the greatest anticholinergic and sedation side effects.
Cyclobenzaprine can reduce pain severity and muscle tightness. Physical or massage therapy may enhance cyclobenzaprine benefits. As with the TCAs, cyclobenzaprine is contraindicated in patients receiving MAO inhibitor therapy within 14 days, cardiac patients, and hyperthyroidism. Doxepin is not as sedating as amitriptyline and cyclobenzaprine for many patients, and is available as a liquid to ease in administering low doses. Its contraindications are the same as for TCAs, plus glaucoma and urinary retention.
Trazodone is not a TCA. It may help minimize sleep disturbances, has fewer side effects than TCAs, but will not reduce pain.
Imipramine, desipramine, and nortriptyline are other TCAs that may be helpful alternatives to the above therapies.
The TCA side effects of constipation, dry mouth, increased appetite and weight gain, drowsiness, drug hangover sedation, orthostasis, urinary retention, vivid dreams, and irregular heart beat are bothersome to many patients. Some of these side effects may subside within a few weeks of starting therapy, and their severity will vary with the drug prescribed and the patient.
Antianxiety Medications (4, 17, 18)
· Alprazolam (Xanax) 0.5 mg - 1.5 mg QD
· Clonazepam (Klonopin) 0.5 mg - 1.5 mg HS
· Buspirone (BuSpar) 5 mg - 10 mg QD
Benzodiazepines (BZD) are used in FMS with the hope that the GABA inhibitory response will reduce the pain signals going to the brain, resulting in less pain sensation and better sleep. Also, by reducing the anxiety associated with being chronically ill with CFS or FMS, they may aid sleep. BZDs are contraindicated in psychoses, acute narrow-angle glaucoma, liver disease, and with coadministered ketoconazole and itraconazole due to cytochrome P450 3A inhibition.
Alprazolam is very effective in low daily doses. This dose can be split between morning and bedtime to achieve a lasting effect throughout the day and night. In one study, alprazolam in combination with ibuprofen resulted in a significant improvement in FMS symptoms. Some physicians are concerned about physical dependence resulting from chronic alprazolam use.
Clonazepam is longer acting than alprazolam, so a single bedtime dose is effective. Since clonazepam has anti-convulsant and anti-spasmodic activity, it is helpful in patients that have PLMS. It is also helpful in patients having RLS, temporomandibular dysfunction, night-time teeth grinding or clenching, or muscle twitching.
Buspirone acts on serotonin receptor 1A. It does not modify patient pain or sleep, but aids patients whose anxiety aggravates symptoms. Buspirone is not thought to be addictive.
Sleeping Aids (4, 13,17, 18)
· Zolpidem (Ambien) 10 mg HS
· Levodopa/Carbidopa (Sinemet) 10 mg HS
· Bromocriptine (Parlodel) 2.5 mg QD
· Diphenhydramine HCl (Benadryl)
Zolpidem aids sleep and is reported to increase daytime energy. It decreases night-time awakenings in patients who fall asleep and wake up, but can not get back to sleep. It does not impact pain. Zolpidem should not be taken after 2 AM in order to avoid morning drowsiness. Controversy exists concerning zolpidem’s addictive potential. As a result, some experts recommend it only be taken a maximum of 3 times per week.
Patients having RSL and PLMS suffer from involuntary arm and leg movements throughout the night. Increasing dopamine levels in these patients is sometimes helpful in relieving these symptoms. Patients taking carbidopa with levodopa (Sinemet) have fewer side effects than those patients taking levodopa alone. The side effects most commonly reported include mood swings, anxiety, dizziness, and constipation. They may decrease over time. If side effects remain intolerable, clonazepam may be a good alternative therapy to try.
Bromocriptine stimulates dopamine receptors, and is currently under evaluation for treatment of CFS and FMS. It may help control RLS and PMLS. Studies show bromocriptine reduces symptoms of anxiety, daytime fatigue, and altered immune function in premenstrual syndrome and lupus patients. Nasal congestion and stuffiness are the main side effects reported with bromocriptine usage. Patients may dose bromocriptine during the day, if nasal congestion interferes with sleep, or may consider taking diphenhydramine at night with bromocriptine to relieve this side effect. Diphenhydramine will not improve sleep quality, pain, or other symptoms. It should only be taken as needed in order to remain effective as a sleep aid.
Selective Serotonin Reuptake Inhibitors (SSRIs) (3, 9, 17, 18)
· Fluoxetine (Prozac) 10 mg - 25 mg Q AM
· Sertraline (Zoloft) or Paroxetine (Paxil) 10 mg - 25 mg QD
· Nefazodone (Serzone)
SSRIs show mixed results in CFS and FMS therapy studies, with many studies showing no benefit. In general, SSRIs interfere with sleep. Some patients report that small daily doses of SSRIs increase patient energy and reduce pain. Due to the long duration of action of SSRIs, however, many patients experience sleep disturbances even at low doses. SSRIs are contraindicated in patients receiving MAO inhibitor therapy within 14 days, and fluvoxamine should not be coadministered with astemizole or cisapride. Patients also report a diminished sex drive.
Fluoxetine is usually dosed at breakfast with the goal of reducing daytime fatigue and decreasing pain. Its use remains very controversial. Sertraline and paroxetine are alternatives to fluoxetine that may not impact sleep as much as fluoxetine, but should not be continued if benefits are not realized after 2 or 3 weeks of use. Paroxetine is the most potent of these 3 SSRIs, and is thought to produce an enhanced analgesic or pain reducing effect. Paroxetine’s effect on sleep is unknown, but it may improve daytime memory and concentration.
Nefazodone is not a SSRI, but may be a helpful alternative to SSRI therapy. It acts primarily at serotonin receptor site 2, and partially at site 1A. It also boosts norepinephrine levels. Dosing is investigative at this time, but minimal doses should be initiated and gradually increased. It enhances alertness, but reduced doses may be needed if patients report impaired cognitive or memory functions. It is contraindicated in patients receiving MAO inhibitor therapy within 14 days, should not be coadministered with astemizole, and is reported to cause nausea and headaches.
Other Neuromodulating Drugs (17, 18)
· Baclofen (Lioresal) 10 mg - 20 mg HS
· Gabapentin (Neurontin) 100 mg - 300 mg up to TID
· Pemoline (Cylert) 10 mg QD maximum
· Venlafaxine (Effexor) 25 mg QD maximum
Baclofen decreases excitatory neurotransmission signals in nerves, resulting in muscle relaxation and pain reduction. Its side effects include muscle weakness, dizziness, and sedation. Even though the duration of action is 4 to 6 hours, sedation often reduces its use to a bedtime dose.
Gabapentin may help reduce pain symptoms in patients. The side effects of sedation and dizziness require gabapentin be dosed in small amounts at bedtime. It has a half-life of 5 to 9 hours, so it may be dosed up to 3 times a day, once side effects are tolerable.
Pemoline is used to treat narcolepsy and attention deficit disorder. It enhances CNS function without causing cardiovascular disturbances. It has been shown to help fatigue and mental concentration in patients with multiple sclerosis, lupus, and CFS. It is very stimulating for most patients, thus, minimal doses may need to be reduced to half or one quarter to minimize overstimulation.
Venlafaxine inhibits neuronal serotonin and norepinephrine reuptake, and weakly inhibits dopamine reuptake. It is under evaluation as an alternative to TCA therapy, and has side effects of nervousness, sweating, and nausea. It should not be coadministered in patients receiving MAO inhibitor therapy within 14 days, and MAO inhibitors should not be started within 7 days of discontinuing venlafaxine therapy.
Nonsteroidal Anti-inflammatory Drugs (1, 15, 17)
NSAID monotherapy was shown to be ineffective in clinical trials, but combination therapy with either alprazolam or amitriptyline showed enhance pain control in patients. The benefit of NSAIDs in combination with other medications needs further investigation. If a patient has an overlying condition in which inflammation is present, NSAIDs will be beneficial.
Immune System Modulators (17)
Antihistamines that block H2 receptors, classically used to treat stomach ulcers, may increase Stage 4 sleep and enhance immune function. Additional studies are needed to clarify these reports, but CFS and FMS patients may find it helpful to try these medications to control their symptoms. H1 receptor blockers, especially diphenhydramine, also are used to aid sleep.
Hydroxychloroquine (Plaquenil) is prescribed to CFS and FMS patients if they have a high ANA level plus symptoms of Sjogren’s syndrome, lupus, or other autoimmune diseases. Patients starting hydroxychloroquine therapy should have an ophthalmology exam every 6 months to monitor for retina toxicity.
Calcium Channel Blockers (17)
· Verapamil-SR (Calan-SR, Novo-Veramil) 60 mg - 120 mg HS
· Nimodipine (Nimotop) 30 mg QD
The usefulness of these medication in FMS and CFS patients is under study. It is thought that calcium channel blockers may increase the threshold of chronic pain receptors, thus reducing the number that fire throughout the night and interfere with sleep and immune function. One study, which needs duplication, evaluated the use of verapamil-SR for 6 months in 25 CFS patients. It was dosed at night to protect against hazards associated with blood pressure drops and dizziness. Immune system improvements were noted, as were enhanced memory, and reduced fatigue and muscle pain.
Nimodipine has been used in several patients, with reports of decreased pain sensitivity, increased energy level, exercise tolerance and mental clarity. It acts primarily on cerebral arteries, has few side effects, and is dosed in the morning. Patients responding to nimodipine therapy show improvements within 4 days. The main patient complaint associated with nimodipine is its cost.
Combination Therapies (17)
Fluoxetine and amitriptyline combination therapy was reported to be more beneficial in reducing symptoms than either drug in monotherapy. Doxepin and clonazepam have been reported to enhance sleep better than monotherapy.
Pain Relief (1, 4, 8, 13, 15, 17)
OTC pain relievers seldom aid FMS pain. For bad flare-ups prescription medication is needed, but opioids often do not offer much relief. Tramadol (Ultram) works by increasing serotonin and norepinephrine release into the spinal cord to inhibit pain perception, in addition to activating the opioid receptors. A tramadol dose of 50 mg BID often produces intolerable side effects of dizziness, nausea, constipation, and headaches in patients. Taking one half a tablet (25 mg) BID or TID often is helpful to such patients. The addiction potential of tramadol is controversial.
Trigger point injections have been helpful for many patients. One to 2 ml of 1% lidocaine with or without 40 mg hydrocortisone suspension may be injected into trigger points for incapacitating areas of focal tenderness. Patients usually benefit the most from concurrent daily deep tissue massage and muscle stretches. Injection sites should be limited to 1 or 2 areas at a time.
Controversies abound with respect to the best approach to pain relief. Some physicians suggest corticosteroids, immunosuppressive drugs, and narcotic analgesics should be contraindicated in FMS patients because the associated drug withdrawal syndromes mimic FMS symptoms. Others report that these medications are generally ineffective, and should be avoided due to their side effect profiles.
Finally, there were no benefits found from treating CFS patients with acyclovir in a controlled study. Additional studies are needed. (19)
There are, however, a host of other medications that are available. Find the one that works for you and stick with it as long as it works.
Treatment of CFS and FMS
Since the etiologies of CFS and FMS are so vague, there currently is no consensus on how the outcomes to clinical interventions should be measured. There are many different aspects of CFS and FMS that researchers are studying. As a result, these studies are conducted using varying methods to measure different outcomes, with the tools used to measure the outcomes also differing. This makes reproducing study results, and comparing the results of various studies, difficult. As more is understood about the etiologies of CFS and FMS, and consensus is reached on how to conduct research studies and measure specific outcomes, the treatment of CFS and FMS will become better defined. (9)
The goal of CFS and FMS therapies is to improve patient symptoms. Specifically, the objectives of treatment should be to: 1) improve pain control and improve the quality of sleep, 2) minimize fatigue to enhance or maintain patient functionality at work and/or at home, and 3) minimize the suffering and distress often observed in FMS patients. (9, 13, 17)
The approaches to treating CFS and FMS are very similar, since the syndromes have many overlapping characteristics. A short review of the role of some endogenous substances thought to play a role in CFS and FMS will be helpful in understanding the rationales behind some of the therapies.
Serotonin (S): S is needed for sleep regulation and induction of Stage 4 sleep. Eight different S receptors are known to date, explaining why some S altering therapies work, and others do not. S is also involved in pain regulation. It is involved in setting the sensory pain threshold in the thalamus, with a deficiency resulting in lowered pain threshold. Some references claim S is a pain inhibitor. S impacts immune function, and the vasomotor and temperature control centers in the brain. Low levels of serotonin in the CNS are associated with depression. (3, 4, 12, 13, 17)
Norepinephrine (N): N is a major neurotransmitter involved with regulating the ANS. It also is needed for sleep regulation, and to induce Stage 4 sleep. N is active in pain regulation and thought to inhibit pain sensation. Its role in immune function is under study. (4, 13, 17)
Dopamine (D): Low brain levels of D may contribute to sleep arousal conditions, such as restless leg syndrome (RLS) and periodic limb movements during sleep (PLMS). Both of these conditions are reported in CFS and FMS patients. (17)
GABA (G): G slows down CNS nerve impulses that may interfere with sleep. (17)
Interleukin-1 (IL-1): IL-1 is an immune system cytokine that is essential to promoting sleep. (17)
Pharmacological Treatments
In general, FMS patients take an average of 3 of the following medications: NSAID - 33% of patients, antidepressant - 69% of patients, muscle relaxant - 13% of patients, benzodiazepine - 15% of patients, occasional narcotic analgesic - 37% of patients. (8) The medications prescribed to treat CFS and FMS typically are not officially indicated for this use. Below is a summary of medications commonly used to treat CFS and FMS, the drug dosages most often used in CFS and FMS patients, the side effects most often reported by these patients, and counseling points that may be helpful. References 2, 3, 5, 9, 12 and 17 provide a more comprehensive discussion of CFS and FMS pharmacological therapies. See Reference 18 for detailed dispensing information for each of the medications discussed.
Tricyclic Antidepressants (TCAs) (1, 4, 8, 13, 17, 18)
· Amitriptyline (Elavil, Endep) 5 mg - 25 mg HS
· Cyclobenzaprine (Flexeril) 5 mg - 40 mg HS
· Doxepin (Sinequan, Adapin) 1 mg - 25 mg HS
· Trazodone (Desyrel) 50 mg - 150 mg HS
TCAs increase brain serotonin and/or norepinephrine levels, and block histamine and/or acetylcholine to varying degrees. For a detailed comparison of these medications, see references 17 and 18. Research on TCAs evaluates their impact on the amount of time spent in quality deep sleep, the number of arousal disturbances during sleep, and the overall impact on patient symptoms. Although the results of the studies are not definitive, several controlled studies showed that TCAs reduce symptoms in a significant number of patients. TCAs are contraindicated in patients that experience PLMS because they can make patients feel worse. They are also contraindicated in patients receiving MAO inhibitor therapy within 14 days, and in narrow-angle glaucoma. Caution is recommended in patients having a seizure history, urinary retention, cardiac problems, psychiatric conditions, and patients that are hyperthyroid or taking thyroid medication.
Amitriptyline is the most commonly prescribed TCA. It benefits about 25% of FMS patients in the areas of pain, stiffness, fatigue, and sleep disturbances. It seems less effective in patients having FMS symptoms for more than 5 years. Therapy should be initiated at the lowest dose possible, preferably on the last day of the work week (Friday for most people). If drug hangover is a problem, take the dose earlier in the evening, rather than before bedtime. It takes up to 1 month to experience maximum therapeutic benefits. Amitriptyline is the TCA that has the greatest anticholinergic and sedation side effects.
Cyclobenzaprine can reduce pain severity and muscle tightness. Physical or massage therapy may enhance cyclobenzaprine benefits. As with the TCAs, cyclobenzaprine is contraindicated in patients receiving MAO inhibitor therapy within 14 days, cardiac patients, and hyperthyroidism. Doxepin is not as sedating as amitriptyline and cyclobenzaprine for many patients, and is available as a liquid to ease in administering low doses. Its contraindications are the same as for TCAs, plus glaucoma and urinary retention.
Trazodone is not a TCA. It may help minimize sleep disturbances, has fewer side effects than TCAs, but will not reduce pain.
Imipramine, desipramine, and nortriptyline are other TCAs that may be helpful alternatives to the above therapies.
The TCA side effects of constipation, dry mouth, increased appetite and weight gain, drowsiness, drug hangover sedation, orthostasis, urinary retention, vivid dreams, and irregular heart beat are bothersome to many patients. Some of these side effects may subside within a few weeks of starting therapy, and their severity will vary with the drug prescribed and the patient.
Antianxiety Medications (4, 17, 18)
· Alprazolam (Xanax) 0.5 mg - 1.5 mg QD
· Clonazepam (Klonopin) 0.5 mg - 1.5 mg HS
· Buspirone (BuSpar) 5 mg - 10 mg QD
Benzodiazepines (BZD) are used in FMS with the hope that the GABA inhibitory response will reduce the pain signals going to the brain, resulting in less pain sensation and better sleep. Also, by reducing the anxiety associated with being chronically ill with CFS or FMS, they may aid sleep. BZDs are contraindicated in psychoses, acute narrow-angle glaucoma, liver disease, and with coadministered ketoconazole and itraconazole due to cytochrome P450 3A inhibition.
Alprazolam is very effective in low daily doses. This dose can be split between morning and bedtime to achieve a lasting effect throughout the day and night. In one study, alprazolam in combination with ibuprofen resulted in a significant improvement in FMS symptoms. Some physicians are concerned about physical dependence resulting from chronic alprazolam use.
Clonazepam is longer acting than alprazolam, so a single bedtime dose is effective. Since clonazepam has anti-convulsant and anti-spasmodic activity, it is helpful in patients that have PLMS. It is also helpful in patients having RLS, temporomandibular dysfunction, night-time teeth grinding or clenching, or muscle twitching.
Buspirone acts on serotonin receptor 1A. It does not modify patient pain or sleep, but aids patients whose anxiety aggravates symptoms. Buspirone is not thought to be addictive.
Sleeping Aids (4, 13,17, 18)
· Zolpidem (Ambien) 10 mg HS
· Levodopa/Carbidopa (Sinemet) 10 mg HS
· Bromocriptine (Parlodel) 2.5 mg QD
· Diphenhydramine HCl (Benadryl)
Zolpidem aids sleep and is reported to increase daytime energy. It decreases night-time awakenings in patients who fall asleep and wake up, but can not get back to sleep. It does not impact pain. Zolpidem should not be taken after 2 AM in order to avoid morning drowsiness. Controversy exists concerning zolpidem’s addictive potential. As a result, some experts recommend it only be taken a maximum of 3 times per week.
Patients having RSL and PLMS suffer from involuntary arm and leg movements throughout the night. Increasing dopamine levels in these patients is sometimes helpful in relieving these symptoms. Patients taking carbidopa with levodopa (Sinemet) have fewer side effects than those patients taking levodopa alone. The side effects most commonly reported include mood swings, anxiety, dizziness, and constipation. They may decrease over time. If side effects remain intolerable, clonazepam may be a good alternative therapy to try.
Bromocriptine stimulates dopamine receptors, and is currently under evaluation for treatment of CFS and FMS. It may help control RLS and PMLS. Studies show bromocriptine reduces symptoms of anxiety, daytime fatigue, and altered immune function in premenstrual syndrome and lupus patients. Nasal congestion and stuffiness are the main side effects reported with bromocriptine usage. Patients may dose bromocriptine during the day, if nasal congestion interferes with sleep, or may consider taking diphenhydramine at night with bromocriptine to relieve this side effect. Diphenhydramine will not improve sleep quality, pain, or other symptoms. It should only be taken as needed in order to remain effective as a sleep aid.
Selective Serotonin Reuptake Inhibitors (SSRIs) (3, 9, 17, 18)
· Fluoxetine (Prozac) 10 mg - 25 mg Q AM
· Sertraline (Zoloft) or Paroxetine (Paxil) 10 mg - 25 mg QD
· Nefazodone (Serzone)
SSRIs show mixed results in CFS and FMS therapy studies, with many studies showing no benefit. In general, SSRIs interfere with sleep. Some patients report that small daily doses of SSRIs increase patient energy and reduce pain. Due to the long duration of action of SSRIs, however, many patients experience sleep disturbances even at low doses. SSRIs are contraindicated in patients receiving MAO inhibitor therapy within 14 days, and fluvoxamine should not be coadministered with astemizole or cisapride. Patients also report a diminished sex drive.
Fluoxetine is usually dosed at breakfast with the goal of reducing daytime fatigue and decreasing pain. Its use remains very controversial. Sertraline and paroxetine are alternatives to fluoxetine that may not impact sleep as much as fluoxetine, but should not be continued if benefits are not realized after 2 or 3 weeks of use. Paroxetine is the most potent of these 3 SSRIs, and is thought to produce an enhanced analgesic or pain reducing effect. Paroxetine’s effect on sleep is unknown, but it may improve daytime memory and concentration.
Nefazodone is not a SSRI, but may be a helpful alternative to SSRI therapy. It acts primarily at serotonin receptor site 2, and partially at site 1A. It also boosts norepinephrine levels. Dosing is investigative at this time, but minimal doses should be initiated and gradually increased. It enhances alertness, but reduced doses may be needed if patients report impaired cognitive or memory functions. It is contraindicated in patients receiving MAO inhibitor therapy within 14 days, should not be coadministered with astemizole, and is reported to cause nausea and headaches.
Other Neuromodulating Drugs (17, 18)
· Baclofen (Lioresal) 10 mg - 20 mg HS
· Gabapentin (Neurontin) 100 mg - 300 mg up to TID
· Pemoline (Cylert) 10 mg QD maximum
· Venlafaxine (Effexor) 25 mg QD maximum
Baclofen decreases excitatory neurotransmission signals in nerves, resulting in muscle relaxation and pain reduction. Its side effects include muscle weakness, dizziness, and sedation. Even though the duration of action is 4 to 6 hours, sedation often reduces its use to a bedtime dose.
Gabapentin may help reduce pain symptoms in patients. The side effects of sedation and dizziness require gabapentin be dosed in small amounts at bedtime. It has a half-life of 5 to 9 hours, so it may be dosed up to 3 times a day, once side effects are tolerable.
Pemoline is used to treat narcolepsy and attention deficit disorder. It enhances CNS function without causing cardiovascular disturbances. It has been shown to help fatigue and mental concentration in patients with multiple sclerosis, lupus, and CFS. It is very stimulating for most patients, thus, minimal doses may need to be reduced to half or one quarter to minimize overstimulation.
Venlafaxine inhibits neuronal serotonin and norepinephrine reuptake, and weakly inhibits dopamine reuptake. It is under evaluation as an alternative to TCA therapy, and has side effects of nervousness, sweating, and nausea. It should not be coadministered in patients receiving MAO inhibitor therapy within 14 days, and MAO inhibitors should not be started within 7 days of discontinuing venlafaxine therapy.
Nonsteroidal Anti-inflammatory Drugs (1, 15, 17)
NSAID monotherapy was shown to be ineffective in clinical trials, but combination therapy with either alprazolam or amitriptyline showed enhance pain control in patients. The benefit of NSAIDs in combination with other medications needs further investigation. If a patient has an overlying condition in which inflammation is present, NSAIDs will be beneficial.
Immune System Modulators (17)
Antihistamines that block H2 receptors, classically used to treat stomach ulcers, may increase Stage 4 sleep and enhance immune function. Additional studies are needed to clarify these reports, but CFS and FMS patients may find it helpful to try these medications to control their symptoms. H1 receptor blockers, especially diphenhydramine, also are used to aid sleep.
Hydroxychloroquine (Plaquenil) is prescribed to CFS and FMS patients if they have a high ANA level plus symptoms of Sjogren’s syndrome, lupus, or other autoimmune diseases. Patients starting hydroxychloroquine therapy should have an ophthalmology exam every 6 months to monitor for retina toxicity.
Calcium Channel Blockers (17)
· Verapamil-SR (Calan-SR, Novo-Veramil) 60 mg - 120 mg HS
· Nimodipine (Nimotop) 30 mg QD
The usefulness of these medication in FMS and CFS patients is under study. It is thought that calcium channel blockers may increase the threshold of chronic pain receptors, thus reducing the number that fire throughout the night and interfere with sleep and immune function. One study, which needs duplication, evaluated the use of verapamil-SR for 6 months in 25 CFS patients. It was dosed at night to protect against hazards associated with blood pressure drops and dizziness. Immune system improvements were noted, as were enhanced memory, and reduced fatigue and muscle pain.
Nimodipine has been used in several patients, with reports of decreased pain sensitivity, increased energy level, exercise tolerance and mental clarity. It acts primarily on cerebral arteries, has few side effects, and is dosed in the morning. Patients responding to nimodipine therapy show improvements within 4 days. The main patient complaint associated with nimodipine is its cost.
Combination Therapies (17)
Fluoxetine and amitriptyline combination therapy was reported to be more beneficial in reducing symptoms than either drug in monotherapy. Doxepin and clonazepam have been reported to enhance sleep better than monotherapy.
Pain Relief (1, 4, 8, 13, 15, 17)
OTC pain relievers seldom aid FMS pain. For bad flare-ups prescription medication is needed, but opioids often do not offer much relief. Tramadol (Ultram) works by increasing serotonin and norepinephrine release into the spinal cord to inhibit pain perception, in addition to activating the opioid receptors. A tramadol dose of 50 mg BID often produces intolerable side effects of dizziness, nausea, constipation, and headaches in patients. Taking one half a tablet (25 mg) BID or TID often is helpful to such patients. The addiction potential of tramadol is controversial.
Trigger point injections have been helpful for many patients. One to 2 ml of 1% lidocaine with or without 40 mg hydrocortisone suspension may be injected into trigger points for incapacitating areas of focal tenderness. Patients usually benefit the most from concurrent daily deep tissue massage and muscle stretches. Injection sites should be limited to 1 or 2 areas at a time.
Controversies abound with respect to the best approach to pain relief. Some physicians suggest corticosteroids, immunosuppressive drugs, and narcotic analgesics should be contraindicated in FMS patients because the associated drug withdrawal syndromes mimic FMS symptoms. Others report that these medications are generally ineffective, and should be avoided due to their side effect profiles.
Finally, there were no benefits found from treating CFS patients with acyclovir in a controlled study. Additional studies are needed. (19)
