A symptomatic therapy or treatment is usually a drug that addresses a particular
aspect of a disease, but taking it doesn't change the underlying course or limit
the damage caused by the disease. As implied by its name, a symptomatic
treatment will only affect the symptoms, not its cause or etiology. It's usually
aimed at reducing the signs and symptoms for the comfort and well-being of the
patient, but it also may be useful in reducing the consequences and aftereffects
of these signs and symptoms of the disease. In many diseases, even in those
whose etiologies are known (e.g., most viral diseases, such as influenza),
symptomatic treatment is the only one available so far.
Multiple sclerosis (MS) is associated with a variety of symptoms and functional
deficits that result in a range of progressive impairments and handicap.
Symptoms that contribute to loss of independence and restrictions in social
activities lead to continuing decline in quality of life. There are many
medications taken by those with MS to manage specific symptoms, such as
spasticity, fatigue or depression.
It needs to be remembered that even though symptomatic therapies have benefits,
their use is limited by possible side-effects. Beyond side-effects, many common
disabling symptoms, such as weakness, are not helped or aided by drug
treatments. However, neurorehabilitation has been shown to ease the burden of
these symptoms by improving self-performance and independence.
The FDA approved disease-modifying therapies are partially effective against
many forms of MS, the symptomatic treatments are found to be necessary for the
many different symptoms as a result of MS.
Recent Medication Approvals
Jan. 22, 2010
The FDA Approves Ampyra to Improve Walking in
Adults with Multiple Sclerosis
The U.S. Food and Drug Administration today approved Ampyra™
(dalfampridine, formerly known as fampridine) extended release tablets
to improve walking in patients with Multiple Sclerosis (MS). In clinical
trials, patients treated with Ampyra had faster walking speeds than
those treated with an inactive pill (placebo). This is the first drug
approved for this use.
"Trouble with walking is one of the most debilitating problems people
with MS face," said Russell Katz, M.D., director of the Division of
Neurology Products in the FDA's Center for Drug Evaluation and Research.
Ampyra (pronounced amPEERah) is a tablet containing a sustained-release
formula of 4-aminopyridine, which blocks tiny pores, or potassium
channels, on the surface of nerve fibers. This blocking ability may
improve the conduction of nerve signals in nerve fibers whose insulating
myelin coating has been damaged by MS.
Ampyra, when given at doses greater than that recommended (10 milligrams
twice a day), can cause seizures. The most common adverse reactions
reported by patients taking Ampyra in clinical trials include urinary
tract infection, insomnia, dizziness, headache, nausea, weakness, back
pain, balance disorder, swelling in the nose or throat, constipation,
diarrhea, indigestion, throat pain, and burning, tingling or itching of
skin.
Ampyra should not be used in patients with moderate to severe kidney
disease. In these patients, blood levels with the drug approach those
associated with the occurrence of seizures.
Ampyra will be manufactured under licenses from Elan of Dublin, Ireland,
and distributed by Acorda Therapeutics Inc. of Hawthorne, N.Y.
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Symptomatic MS Treatments
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The following list is courtesy of the USCF Multiple Sclerosis Clinic:
Depression
Depression is a very common symptom in MS. Depression is characterized by
feelings of hopelessness, the inability to enjoy things that once were
pleasurable, feelings of worthlessness, disruption of sleep, crying, feelings of
sadness or irritability, social isolation, decreased sexuality, and in some
cases, suicidal thoughts. If these symptoms persist occur every day for two
weeks or more, or include suicidal thoughts, medical attention is required
immediately. Regardless of whether the depression is reactive (i.e., as a result
of having a serious illness), genetic (endogenous depression), or a
manifestation of the illness itself, medications can be helpful. Individual
psychotherapy can also be helpful, either by itself or in combination with
medication. However, studies suggest that in MS patients, depression usually
requires some form of treatment - it's unlikely to spontaneously remit. In
addition to an alteration of mood, depression may contribute to the fatigue
experienced by patients with MS and this also may respond favorably to
antidepressant medications. Useful agents in the treatment of depression include
the selective serotonin reuptake inhibitors (e.g., fluoxitine [Prozac], 20-80
mg/day or sertraline [Zoloft], 50-200 mg/day), the tricyclic antidepressants
(e.g., amitriptyline [Elavil], 25-150 mg/day; nortryptiline [Pamelor], 25-150
mg/day; or desipramine [Norpramin],100-300 mg/day), and the non-tricyclic
antidepressants (e.g., venlafaxine [Effexor], 75-225 mg/day).
Fatigue
Fatigue is characterized by diminished energy and endurance. Many patients with
MS also experience an overwhelming sense of exhaustion that requires them to
sit, recline, or fall asleep. This symptom is often aggravated by elevated
temperature and can be reversed by cooling. Fatigue in MS can be severe and
disabling. It affects almost 90% of patients to some degree and is characterized
as moderate to severe in over half. It accounts (in part or in whole) for the
disability in approximately 65% of patients unable to work. It is also
multifactorial. Thus, depression can often contribute to a patients fatigue and
may be managed successfully with anti-depressant medications. Patients who
expend exceptional effort to accomplish basic ADLs may experience substantial
fatigue and may benefit from assistive devices, from help in the home, or from
successful management of their spasticity. Not infrequently, patients with MS
have nighttime sleep disturbances that translate into day time fatigue. As one
example, patients with frequent nocturia (and, thus, frequent nocturnal
awakenings) may benefit from an anticholinergic medication at bedtime to prevent
these night time arousals and improve the quality of their night time rest. In
addition to these other sources of fatigue in MS, however, there is also an
extreme lassitude that is more specifically related to the disease. This fatigue
can be the sole manifestation of an attack and is often difficult to treat.
Several effective medications are now available for the treatment of fatigue.
These medications include amantadine (Symmetrel) 200 mg/day; pemoline (Cylert)
37.5-75 mg/day; methylphenidate (Ritalin) 5-25 mg q day, and modafinil
(Provigil) 200-400 mg/day. A cooling vest or cap may be helpful when symptoms
are provoked by exposure to elevated temperatures.
Spasticity
Spasticity (muscle stiffness) is usually accompanied by weakness, slowness of
movement, poor coordination, and spontaneous spasms. Spasticity poses a
considerable problem for the management of MS patients. Over 40% of patients
describe their spasticity as moderate to severe. Typically it is most severe in
the lower extremities and often interferes substantially with a patients ability
to ambulate, to work, and to perform even the most basic activities of daily
living. It's often painful and frequently associated with painful extensor
(occasionally flexor) spasms. At times, however, the increased stiffness of the
muscles may be helpful to patients by providing non-volitional support during
ambulation. In such a circumstance, overly aggressive treatment may actually do
more harm than good. Non-pharmacological approaches to the management of
spasticity include physical therapy, regular exercise, and stretching, which can
provide substantial relief. The avoidance of nociceptive inputs from a variety
of sources (e.g., infections, fecal impactions, bed sores, etc.) is an extremely
important first principal in patient management because such inputs are known to
increase markedly the severity and extent of spasticity. Effective
pharmacological agents for reducing both spasticity and spasms include lioresal
(Baclofen) 20-120 mg/day; diazepam (Valium) 2-40 mg/day, and tizanidine
(Zanaflex) 8-32 mg/day. Several other medications have also been reported to
provide occasional benefit for patients with spasticity including clonazepam,
carbamazepine, phenytoin, gabapentin, tetrahydrocanabinol, barbiturates, and
alcohol. However, the efficacy of these agents is not well established.
When the spasticity is particularly severe and the patient already has limited
use of their lower extremities, a surgically implanted lioresal (Baclofen) pump
(delivering the medication directly into the spinal fluid that bathes the spinal
cord) can often provide substantial relief. This may also allow for improved
hygiene and, thereby, reduce the frequency of urinary infections and bed sores.
Destructive procedures such as selective rhyzotomy, tenotomy, myotomy, and
phenol injections should be reserved for only the most extreme cases that are
unresponsive to other measures.
Pain
Pain is an under appreciated symptom of MS. Over half of MS patients complain of
pain and, in a substantial fraction, the pain is described as severe, at least
at times. MS-related pain can be experienced as jolts of electricity, continuous
dull burning, disagreeable tingling, or raw sensations. An improved
understanding of the mechanisms that produce pain of central origin has produced
several successful approaches to its management, including the anticonvulsant
drugs (e.g., carbamazepine [Tegretol], 100-1000 mg/day or phenytoin [Dilantin],
300-600 mg/day or gabapentin [Neurontin], 300-3600 mg/day), or the
antidepressant drugs (e.g., amitriptyline [Elavil], 25-150 mg/day or
nortryptiline [Pamelor], 25-150 mg/day or desipramine [Norpramin],100-300 mg/day
or venlafaxine [Effexor], 75-225 mg/day), or the anti-arrhythmic drugs (e.g.,
Mexiletine [Mexitil], 300-900 mg/day). If these treatments are unsuccessful,
some patients may respond to a comprehensive pain management program. Such
persons may be referred to the UCSF Clinical Pain Research Center.
Ataxia/Tremor
Ataxia/Tremor is a common and often intractable symptom in MS that is difficult
to treat effectively. Tremor may involve the hand, arm, leg, head, or voice.
These movements may be barely noticeable or they can be severely incapacitating.
Some medications are occasionally helpful including clonazepam (Klonopin),
1.5-20 mg /day, mysoline (Primadone) 50-250 mg/day, propranalol (Inderal) 40-200
mg/day, or ondansetron (Zofran) 8-16 mg/day. The use of weights on the wrists
may occasionally reduce tremor in the arm or hand. Unfortunately, however, the
success of most attempts at therapy is limited. Recently, there has been
interest in the use thalamotomy and/or the placement of deep brain stimulators
to control tremor. However, even in the best of hands the response to this
intervention is often partial, the response rate is limited (~50%), the duration
of any therapeutic benefit is unknown. Moreover, the surgical procedure itself
carries risk.
Bladder Dysfunction
Several different types of bladder dysfunction occur in MS. Not infrequently,
different types of dysfunction co-exist in the same patient and, as a result,
urodynamic testing can often provide useful clinical information. During normal
reflex voiding there is a coordinated relaxation of the bladder sphincter that
is precisely timed to the detrusor muscle (bladder wall) contraction. The
urinary stream is stopped by a reversal of the above mechanisms with bladder
wall relaxation coordinated with sphincter contraction. The bladder reflex is
activated by stretch of the bladder wall during filling and it can be
voluntarily inhibited. Symptoms of bladder dysfunction are present in over 90%
of patients with MS. Many of these symptoms occur only occasionally and are
quite mild. In this circumstance, they don't require specific intervention.
Nevertheless, over 30% of MS patients experience bladder symptoms of sufficient
severity to result in episodes of incontinence weekly or more often.
Fortunately, bladder symptoms are among the easiest MS symptoms to treat. These
symptoms include (1) urinary frequency the need to go to the bathroom
frequently; (2) urgency the need to go to the bathroom immediately; (3)
hesitancy difficulty initiating the urine stream; and (4) retention the
inability to completely empty the bladder. Most patients can regain continence
or experience significant improvement in these symptoms.
The first type of bladder dysfunction, results from decreased inhibition of the
bladder reflex. Symptomatically, this decrease causes urinary frequency (having
to urinate more often than usual), urinary urgency (having to get to the
bathroom right away when you feel the urge), and uncontrolled bladder emptying
(incontinence). When these symptoms are mild they can sometimes be treated with
fluid management techniques such as evening fluid restriction to prevent night
time incontinence or the use of frequent voluntary voiding to prevent day time
incontinence. If these simple approaches fail to control the problem, however,
there are several medications available that can inhibit bladder wall
contraction and thereby lessen the bladder reflex. These medications include
propantheline bromide (ProBanthine) 10-15 mg/day; oxybutinin (Ditropan) 5-15
mg/day, hycosamine sulfate (Levsin) 0.5-0.75 mg/day and tolteridine tartrate
(Detrol) 2-4 mg/day. Often the co-administration of an over-the-counter
medication such as pseudoephedrine (Sudafed, 30-60 mg) which cause contraction
of the bladder sphincter can help maintain continence.
The second type of bladder dysfunction, results from the loss of coordination
and synchronization between the bladder wall and sphincter muscles
(dyssynergia). This results in a difficulty initiating or stopping the urinary
stream (hesitancy) and leads to the retention of residual urine in the bladder
following voiding. Occasionally, this condition will respond to medications such
as phenoxybenzamine (Dibenzyline, 10-20 mg/day) but more often this condition
requires the use of intermittent or continuous catheterization. A third type of
dysfunction, loss of reflex bladder wall contraction, generally results from a
chronically over-filled bladder, which, itself, is often due to long-standing
dyssynergia. This condition can occasionally respond to medications such as
bethanecol (Urecholine), 30-150 mg/day, but often this condition also often
requires intermittent or continuous catheterization.
It's also important to monitor patients for urinary tract infections and treat
them promptly when they are identified. Patients who have large volumes of
post-void residual urine in their bladders are predisposed to bladder infections
and patients at risk for such complications may be identified by measuring a
post-void residual volume. It's also often helpful to take steps to prevent
infections. Acidification of the urine with cranberry juice or Vitamin C
inhibits some bacteria. Prophylactic administration of antibiotics is sometimes
necessary but may lead to bladder colonization by resistant organisms and can
result in infections that are more difficult to treat. Intermittent
catheterization may be necessary to allow complete bladder emptying and to
prevent recurrent infections.
Bowel Dysfunction
Constipation is a common symptom in MS, occurring in over 30% of patients. High
fiber diets (often with supplemental fiber) in addition to plenty of fluids is
usually the best approach. Natural or other laxatives can also help. Fecal
incontinence is much less common than constipation although 17% of patients
(more so in men) report at least some episodes. If it's severe enough to warrant
treatment, fecal incontinence may respond to a reduction in total dietary fiber.
Paroxysmal Symptoms
Several different paroxysmal syndromes occur in MS. These syndromes are
distinguished by brief duration (30 seconds to 2 minutes); high frequency of
occurrence (5-40 paroxysms/day); lack of any alteration of consciousness or
change in background EEG during the events; a self-limited nature (generally
lasting only months and then subsiding). They may be precipitated by
hyperventilation or movement. These syndromes include the familiar L-Hermitte's
sign (electric shock like sensations induced by neck flexion), tonic seizures,
paroxysmal dysarthria/ataxia, paroxysmal sensory disturbances, and several other
less well characterized syndromes. These syndromes are also distinguished by
their marked responsiveness to very low dosages of anticonvulsant medications
such as carbamazepine (Tegretol), 50-400 mg/day, phenytoin (Dilantin), 50-300
mg/day, or acetazolamide (Diamox) 200-600 mg/day. Patients with MS may also
suffer from trigeminal neuralgia (tic douloureux) which often responds to
similar medications.
Heat Sensitivity
Many symptoms are aggravated by exposure to heat or with fever. Keeping away
from the direct heat of the sun and the use of air conditioning are often
necessary to prevent these symptoms. Cooling vests or caps may be useful in
select patients.
Weakness
The potassium channel blockers (e.g., 4-amino pyridine, 10-40 mg/day; and
3,4-di-amino pyridine, 40-80 mg/day) may help some MS symptoms (especially heat
sensitive symptoms) and anecdotally some patients experience improved function.
These drugs presumably work by prolonging the duration of the nerve action
potential and, thereby, facilitating conduction through demyelinated fibers. At
high enough doses they may also cause seizures for similar reasons. These agents
are not FDA-approved but are currently available from one of several compounding
pharmacies around the US. More definitive clinical trials, however, are needed
to establish any therapeutic benefit.
Sexual Dysfunction
Sexual dysfunction was reported by over 60% of the women and over 75% of the men
in a recent survey of MS patients in northern California. The greater
dysfunction in men resulted not only from impotence (61%) but also from less
sexual desire and less demonstrated interest by their partners. Nevertheless,
sexual dysfunction can be a considerable problem for either gender. Women
experiencing sexual dysfunction often experience numbness in the genital area,
diminished orgasmic response, unpleasant sensations, and diminished vaginal
lubrication. Men commonly report impaired genital sensation, delayed
ejaculation, decreased force of ejaculation, and/or inability to achieve and
maintain an erection. Approaches such as couples or psychological therapy may
help in selected cases. Communication between partners is essential. Teaching
your partner how you need to be touched or positioned can result in a return of
pleasure and excitement instead of discomfort or pain. The use of water soluble
lubricants may be an essential aid in genital stimulation and sexual arousal.
The use of vibrators may provide pleasurable and sexually stimulating
sensations. Spasms, pain, spasticity, fatigue, and bladder/bowel dysfunction may
contribute to sexual dysfunction, and medications to alleviate these symptoms
may help. Thus, the effective management of adductor spasticity, the use of
devices (e.g., vibrators) to make up for loss of deep sensation, penile
injections of papaverine or prostaglandin, or prosthetic devices to assist with
maintaining erection may also be helpful in some circumstances. The biggest
advance in treatment of impotence, however, has been the introduction of
sildenafil (Viagra) 50-100 mg orally 1-2 hours prior to sex.
Memory Problems
Cognitive problems, including problems with memory, are common in MS. Between
45% and 65% of people with MS will have some problems with cognitive
functioning. Donepezil HCl (Aricept) is a cholinesterase inhibiting medication
used to treat patients with early Alzheimers disease. Two small, non-randomized,
uncontrolled studies have shown benefit for MS patients with memory problems
taking 10 mg/day. Similar small, uncontrolled studies have also shown benefits
for patients with memory problems due to traumatic brain injury. Larger,
placebo-controlled studies are underway with both these populations. While this
medication is not currently approved by the FDA for the treatment of memory
problems in patients with MS, it may be of some benefit in some cases.
The following are some of the medications used to treat many of the symptoms
caused by MS:
|
MS Symptoms |
Common Medications |
|
|
Walking |
Ampyra (Dalfampridine) |
|
|
Spasticity |
Baclofen (Lioresal)
Diazepam (Valium)
Clonazepam (Klonopin)
Dantronlene (Kantrium) |
|
|
Muscular or Flexor Spacticity & Joint Spacticity |
Dantrolene (Dantrium)
Tizanidine (Zanaflex)
Ibuprofen
Anti-inflammatory |
|
|
Optic Neuritis |
Methylprodnisolone (Solu-Medrol)
Oral Steroids |
|
|
Fatigue |
Amantadine (Symmetrel)
Fluoxetine (Prozac)
Pemoline (Cylert)
Mondafinil (Provigil)
Armodafinil (Nuvigil)
Antidepressants |
|
|
Pain |
Celecoxib (Celebrex)
Aspirin or acetaminophen
Antidepressants
Codeine |
|
|
Pain (Neuropathic) |
Duloxetine Hydrochloride |
|
|
Pain (Dyesthesias) Burning Aching Pain |
Phenytoin (Dilantin)
Gabapentin (Neurontin)
Gabapentin (Neurontin)
Amitriptyline (Elavil)
Acetaminophen |
|
|
Pain (Paresthesias) |
Amitriptyline (Elavil)
Nortriptyline (Pamelor) |
|
|
Pain (Trigeminal Neuralgia) |
Carbamazepine (Tegretol)
Phenytoin (Dilantin)
Anticonvulsants |
|
|
Tremor |
Isoniazid (Laniazid / Nydrazid) |
|
|
Tremor Pain Spasticity |
Clonazepam (Klonopin) |
|
|
Paroxysmal Itching |
Hydroxyzine (Atarax) |
|
|
Peripheral Neuropathy |
Duloxetine hydrochloride (Cymbalta) |
|
|
L-hermitte's Sign |
Anticonvulsants |
|
|
Depression |
Duloxetine Hydrochloride (Cymbalta)
Venlafaxine (Effexor)
Paroxetine (Paxil)
Sertraline (Zoloft)
Fluoxetine (Prozac)
Bupropion (Wellbutrin)
Remeron (Mirtazapine) |
|
|
Insomnia |
Sleeping Aides |
|
|
Bladder Dysfunction |
Tolterodine (Detrol)
Oxybutynin (Diropan)
Darifenacin (Enablex)
Tamsulosin (Flomax)
Terazosin (Hytrin)
Solifenacin Succinate (Vesicare) |
|
|
Sexual (Erectile) Dysfuntions |
Papaverine
Tadalafil (Cialis)
Vardenafil (Levitra)
Sildenafil (Viagra) |
|
|
Nausea & Dizziness |
Meclizine (Antivert - US / Bonamine - CA) |
|
|
Constipation |
Mineral Oil
Docusate (Colace)
Bisacodyl (Dulcolax) |
|
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