WHAT MEDICATIONS ARE USED FOR M.S. ?



ALL DRUGS HAVE SIDE EFFECTS.
RESEARCH THE RISK/BENEFITS OF ANY DRUG.
DISCUSS YOUR EXPECTATIONS/FEARS WITH YOUR DOCTOR.
If your doctor doesn't discuss these factors get another doctor.

CAVEAT EMPTOR

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WHAT MEDICATIONS?

WARNING:  Many drugs used in the treatment of MS are classified as “off label use” because they are not tested as to effectiveness with MS.  No study to date has tested combined drug therapies. (Sept 99).

The Mayo Clinic (August 2004) suggests Ms patients should take a wait-and-see approach to medications.  Many Ms patients 17% have benign Ms.  The effectiveness of Ms drugs over the course of the disease has not been demonstrated.

Multiple Sclerosis is presently classified as an incurable disease of unknown origin and therefore any drug therapy is for maintenance of the symptoms.

The treatment of MS includes a long list of prescription drugs to control, manage, or suppress the symptoms of the disease. Among the commonly used prescription drugs for MS are the following immunosuppressive drugs: azathioprine (Imuran), cladribine (Leustatin), and Clyclophosphamide (Cytoxan). The use of these drugs for the treatment of MS is controversial because their efficacy is not clearly established and the severe long-term side effects include mutations, sterility, and an increased risk of cancer. Other prescription drugs prescribed include a host of anticonvulsive drugs such as Dilantin, Tegretol, and Lioresal to control tremor and spasticity. Pain medications that are used for MS may include anti-inflammatory drugs such as ibuprofen.  Prescription drugs have a definite use, but these products have not been able to stop the progression or reverse the symptoms of the disease.  63.6% of patients reported using alternative protocols to augment their conventional MS therapy (Winterholler et al. 1997). Persons with MS often use a variety of alternative methods to help with their disease because not much can be done to hold the line against this disease by using prescription drugs.  Some neurologists disagree with this position and the debate continues.

THE CONVENTIONAL DRUGS of America are called the ABC(R&T) drugs Avonex® an interferon beta-1a drug,  Rebif® an interferon beta-1a drug, Betaseron® an interferon beta-1b drug and Copaxone® an glatiramer acetate drug.  The AB's are bata-interferon based drugs enhancing a natural body substance, a type of white blood cell, whereas C is a synthetic amino acid that acts like a decoy.

The use of ABC drugs are based upon a major assumption (theory) that MS is caused by autoreactive T cells. It is important to keep in mind that autoreactive T cells are a symptom of MS and not a cause. Some researchers believe that MS is too erratic to fit the autoimmune models with any satisfaction.

Recent studies suggest MS is not an autoimmune disease and therefore ABC (R) drugs effectiveness is highly suspect.  Current theory suggested in 1996 and confirmed in 2004 suggests Ms is the death of myelin-producing cell by enzymes and/or excitotoxins.  

A breakdown of the blood brain barrier maybe a more closely related symptom to the actual cause(s) of MS.

The ABC drugs were directed towards RRMS patients especially in the early diagnosis period. RRMS has a claimed 66% symptoms improvement rate from recent exacerbations with NO treatment. The results of small populated short term clinical studies of RRMS should be critically questioned. We also need to keep in mind that the MS misdiagnosis rate is still 10-15%.  Some suggest that 2/3 of Ms do not respond to any ABC drug.  Recently the ABC drugs are used for all types of MS.

THE CLAIM:  These drugs decrease the number and severity of relapses, slow the progression of the disease, and decrease the development of new brain lesions.  

THE CRITICS: The effectiveness of this therapy are exaggerated.  Randomized, controlled clinical trials of drugs are problematic.  In conventional medicine, the placebo effect is often disregarded or minimized.  In clinical trials of experimental drugs, the placebo response is simply subtracted from the effect of the drug.  "If placebos were to be acknowledged as effective in their own right, it would expose large gaps in medicine's and in doctors' knowledge about underlying mechanisms of care and relief from suffering."    Dr. Jay Katz. The placebo effect is a response of a person's condition to the placebo.   In 1955 it was known that 35% of people on placebo, symptoms were improved.  Subsequent studies of a variety of medical conditions found the placebo effects were frequently in the 30 to 40% range.  Some studies the placebo was 70% effective.  In MS studies 1935 to 1950 ineffective therapies produced 60 to 70% improvement.  

Histopathologic studies suggest that the pathologic characteristics vary significantly, therapy may have to be individualized. (Sept 99)

England (NICE) says the modest benefits of these ABC drugs do not justify the very high cost of these drugs. July/Dec, 2000    NICE=National Institute for Clinical Excellence for England and Wales.

There is no good evidence that ABC drugs effect the progression of the disease, others disagree.  After 5 years of use there is no evidence to support the claim the Ms patient is less likely to be disabled.

The results of the ABC drug trials have been disappointing, some of the claimed benefits are the result of a placebo effect. NICE 2000  NICE says they reviewed all clinical trials, drug manufacture claims and other sources.  They have deferred final conclusion to July 2001 to allow interested parties to value-add to their evaluation.  The preliminary conclusion is there is insufficient evidence to support the general use of the ABC drugs.

Neurologists are inconsistent in the application of the ABC drugs.

Neurologists are divided over the benefits of the ABC drugs.  Most agree that the drugs may not slow the progression of the disease but many maintain they reduce frequency and severity.  Some suggest the ABC drugs should be banned.  Most agree they offer hope but at what cost?

MS societies claim not enough weight has been given to MRI evidence on early disease activity.  The evidence however suggests the relationship of MRI to symptoms is presently wanting.  They also claim the possibility that long term benefits could be underestimated.

Some suggest the modest benefit only justify about a $2,500 cost per patient year whereas the ABC drugs cost $25,000 cost per patient year.  They believe other more cost effective alternatives exist.

Feb 2002, Britons to get Ms drugs under cost-sharing scheme.  If drugs are not effective then cost of drugs will be reduced on a sliding scale by the manufacturing companies.  They expect to assess 30,000 Ms patients and only about 10,000 are expected to be eligible for therapy.  This is basically a live ongoing study of Ms therapy.  It will be interesting to see what % of the 10,000 will get benefit and how much.  This innovative approach could revolutionize medicine.  Only pay for measurable results.

Because of the placebo effect and the fact that MS may remain stable with no therapy or that full recovery may occur after an MS attack, it is important not to rely heavily on treatment benefits based on short term studies.  A 20 to 40 year study is required to determine effectiveness.  

Study verification of drugs should be taken out of the hands of Drug Companies and the doctors involved in establishing guidelines on disease treatment must not have financial ties to the pharmaceutical industry.   

BATA  INTERFERON: (AB- DRUGS)

Interferon is composed of Alpha, Bata and Gamma.  Gamma-interferon, produced by activated lymphocytes ( a type of white blood cell) may provoke flares in MS patients.  Gamma-interferon is normally produced as part of the body defense system against viral infections.  This may explain why MS patients with respiratory infections (colds) have MS flares.  There is no interferon on normal controls present in MS lesions during active disease process.

Viral pneumonia usually produces high levels of gamma interferon
Bacterial infection usually produces low levels of gamma interferon

 BENEFIT CLAIMS  used to reduce frequency and severity of relapses in RRMS with disability of 5.5 or less.
Both types of drugs claim 30% reduction frequency and severity, 50% reduction of brain lesions but no significant slowing of progression.

The exact therapeutic mechanism and long-term benefits aren't fully understood. They haven't been conclusively proven to prevent permanent disability.
  Some studies claim a delay in progression of  9-12 months, 40% claimed no delay
  The third year tests showed no change between placebo and betaseron groups
Some 30% of patients develop antibodies towards the drugs after one year of use.

There is no proof that interferon's have benefits for SPMS or PPMS (UK Sept 99)

The Black Hole Study suggests a 45% reduction using Betaseron T1 with SPMS in the development of black holes that are associated with axonal damage. Switzerland May 2000

SIDE EFFECTS
 
85% injection site reaction
84% headache
76% flu like symptoms – Ibuprofen used to reduce symptoms
52% Pain
35% Dizziness
depression
They can’t really do a double blind study as the patient taking the drug usually knows.

62% of drug users had a worsening of the MS condition vs. 74% on placebo having a worsening effect over a two year period.

5% progressed to severe disability vs 14% of the placebo progressed to severe disability. These finding should make one skeptical as RRMS usually don't progress to severe in a 3-5 year period.
Do not use interferon with Cylert or Tegretol

WARNINGS

The UK neurologists do not prescribe interferon for RRMS until there are 2 disabling relapses every two years or greater.  Many Neurologists do not follow this standard. 

During trials one suicide and 4 attempted suicide on Betaseron and zero on placebo,  also 4 spontaneous abortions

Wayne State University concluded a 12 month study of 156 RRMS patients in October 1999 testing the effects of a placebo, Copaxone, Betaserone and Avonex. They concluded that Avonex did not produce statistically significant therapeutic effect.
Avonex - Any alleged benefits were short lived and were all lost within the second year of use.

February 2002 Ms Centre of University Department of Neurosciences in Torino, Italy conducted a head to head study (1999-2001) called an 'Independent Comparison of Interferon Trial' of 188 relapsing-remitting patients with  Avonex and Betaseron and they concluded that Betaseron proved 42 to 58 % more effective than Avonex in curbing relapse, disease progression and number of lesions found on the brain. 

This would reduce the alleged 30% improvement claims to 15% or less supporting the NICE groups concerns.

England and Wales have suspended new patient's use of Beta Interferon and Glatiramer acetate restricted use to those already taking the drug because all evidence suggests modest clinical benefits are outweighted by the very high costs of the drugs. July 2000,  Dec13, 2000 lobby groups want NICE (National Institute for Clinical Excellence) a special health authority for England and Wales established April 1, 1999 by the National Health Service.  They have agreed to review any new data by July 2001.  It is believed they have all ready reviewed clinical trial results and manufacture claims in their original ruling.  If this ruling is overturned by a political decision rather than a scientific medical decision, Ms research and credibility will be set back years. 

Despite these findings neurologists continue to make Avonex® the drug of choice, likely because of financial ties to the pharmaceutical industry.

INTERFERON BETA-1A (AKA AVONEX® & REBIF®)
 

Beta – 1A(IFN-beta-1A) Rebif &  Avonex a 29%- 32% reduction in rate of relapses FDA 1996 approval. Avonex® claims however have proven to be very disappointing by 1999.

REBIF (interferon beta 1a) a higher doses is used to treat second progressive and is in its fourth year of testing and some believe it is showing significant benefits to slowing the progression of MS. (03-2000) The USA Orphan Drug Law allows Avonex and Betaseron to control the market, head to head trials are underway to allow Rebif into the USA.

Betaseron® T1 reduces brain black holes by 45% that are associated with axonal damage but drug is only available in Europe, Canada and Australia. May 2000

INTERFERON BETA-1B (AKA BETASERON & BETAFERON)
 

Beta – 1B (IFNB-1B) Betaseron North America, Betaferon in Europe, used in Canada since 1995, FDA approved 1993 used for RRMS and second progressive.  Flu symptoms are common and Buprofen is some times used to control these symptoms.

NOTE: High levels of suicide are linked to Betaseron.

 

COPAXONE alias COPOLYMER 1 (glatiramer acetate)  

Copaxone is claimed to decrease by 30% MS relapses, and slows the development of  disability.  Reduces brain lesions by 35%.  HOWEVER the brain can show relapsing and remitting lesions by MRI scans without causing clinical symptoms.  A synthetic amino acids that look like mylein and may act as a decoy diverting immune cell attacks on myelin.  Approved in Canada 1997 cost $12.3K/yr wholesale .  Adverse: affects injection site reaction, flushing, chest pains, palpitations, anxiety, duspnea, constriction of the throat and urtic area.  Disease progression is not significantly affected.

Copaxone acts like a universal antigen that stimulates an immune response. 

(2004) Copaxone was not effective in treating Primary Progressive MS.

WARNINGS

Ben-Gurion University's Dr. Anat Ahiron study suggests a copaxone link to breast cancer (2005)

Dr Luca Munari in an independent review suggests Copaxone shows no evidence it slows multiple sclerosis progression.

England and Wales have suspended new patient's use of Beta Interferon and Glatiramer acetate restricted use to those already taking the drug because all evidence suggests modest clinical benefits are outweighed by the very high costs of the drugs.  July 2000,  Dec13, 2000 lobby groups wants NICE (National Institute for Clinical Excellence) a special health authority for England and Wales established April 1, 1999 by the National Health Service.  They have agreed to review any new data by July 2001.  It is believed they have all ready reviewed clinical trial results and manufacture claims in their original ruling. 

TYSABRI (Natalizumab alias Antegren)

This drug is called a selective adhesion molecule inhibitor and claims to slow progression of Ms.  This drug is an antibody that keeps destructive immune cells from moving into the brain, gastrintestinal tract and joints.  It is given by IV once-a-monthe and is believed to inhibit the movement of immune cells across the blood-brain barrier.  It has only had a 2 year trial on RRMs patients.  It is not known if the 35% of RRMs who go benign Ms (according to Mayo Clinic research) are included or eliminated.  They claim 42% reduction in risk of Ms and 67% reduction of rate of clinical relapses. Approximately 1,100 patients with MS had received Tysabri for one year or more.  It is known that flavanoids improve the blood-brain barrier but do not slow progression.  Second year clinical trials will conclude by mid 2005.  

Known risks are infection, pneumonia, depression, gallstones.  Longer term adverse effects are unknown after the first year of trials. 

WARNING

Tysabri had accelerated approval by the FDA for use in November 2004 and has been withdrawn from the market March 28, 2005 and all clinical trials.  There has been adverse events in the Tysabri/Avonex trials.  One event was fatal, one confirmed and one suspected cases of PML (Multifocal Leukoncephalopathy), a  usually fatal demyelination disease.  PML is a rare, serious, progressive neurologic disease, usually occurring in immunosuppressed patients, often resulting in irreversible neurologic deterioration and death. There is no known effective treatment for PML, although reversing immune system suppression may slow or arrest progression of the disease. 

STEROIDS - ADRENOCORTICOIDS  (SYSTEMIC)  

A Corticosteroid, anti-inflammatory (steroidal), immunosuppressant. Claimed to reduce inflammation in nerve tissue and shorten the duration of flare-ups. Used for MS exacerbations but may cause hypertension and carries significant risk.

Steroids are known to inhibit remeyelination and they destroy islet cells that produce insulin

Steroids increase blood sugars and decreases blood potassium.

LONG TERM EFFECT: May lead to glaucoma, cataracts, diabetes,  Osteoporsis, thin skin, funxctional dependence (addiction).  Few studies have documented the risk/benefits of steroid use in MS. Avoid salt and sugar during steroid use.
LIFE-THREATING IF: Hives, rash, intense itching, faintness, swelling soon after a dose.

Steriods shut down the immune system, promote hardening of the arteries, bone loss, obesity and psychosis.

Steroids are the leading cause of death among chronic lupus.

A doctor cannot ethically prescribe a treatment until clinical results are known that the treatment is likely to do more good than harm.

Steroids could well mess up a lot of other promising agents. Its use is stifling development of better drugs. Using the drug for 48 hours after injury could kill patients instead of minimizing risk of paralysis. Steroid use in treating spinal cord injuries could be harmful and does not improve function in patients with spinal injuries, despite clinical trials. Steroids can cause infection and respiratory problems. Alberta trauma doctors and specialists who treat spinal cord injuries have stopped using the drug. The American Association of Neurosurgeons and the Congress of Neurosurgery will address the issue but will not report until February 2002. (10-2000) It makes one wonder about the alleged benefits of steroids for MS.

Generic names – Betamethasone, Cortisone, Dexamethasone, Hydrocortisone (Cortisol),
                             Methylprednisolone, Prednisolone, Prednisone, Trimcinolone

Brand Names – Apo-Prednisone, Aristocort, Betnelan, Betnesol, Celestone, Cortone, Cortone Acetate,
                            Cortel, Cortenema, Cortiform, Decadron, Delta-Cortel, Deltasone, Dernolil, Dexasone,
                            Dexono, Hexadrol, Hydeltrasol, Hydeltra, Hydrocortone, Kenacort, Medrol, Meprolonel,
                            Meticorten, Mymethasone, Nor-Pred-TBA, Oradexon, Orasone, Pediapred, Predisone,
                            Prelone, Sterapred, Winred.

PREDNISONE used for mild to moderate exacerbations.  (99% of UK neuro’s used this drug)  50% used
  no tapering off drug with Prednisone.  Given orally.

90% of severe MS appear to respond to massive doses of steroids given by IV

DEXAMETHASONE given orally.

SOLU-MEDROL (METHYPREONISONE) used in severe exacerbations given intravenously.

AMANTADINE used to treat fatigue.  Confusion or sedation may occur if taken with the herbs Belladonna, Henbane, Pheasant's eye or Scoppolia.

ANTEGREN Natalizumab are in the clinical trials stage in a two prong study, antegren by itself and antegren with avonex.  It is claimed to reduce the number of new lesions in the brain and reduced the number of relapses.  No evidence it slows down progression of the disease.

Antegren inhibits the immune cells from leaving the blood stream therefore diseases kept in check by the immune system like cancer, infections etc. should be watched for in the longer term use of this drug.

Known side effects include headache, nausea, abdominal pain, infection, urinary tract infection, pharyngitas and rash.  

ANTIVIRALS (AMANTIDINE) Antiviral (type A flu), antiparkinsonism, promotes release of neurotransmitter, dopamine within the brain.

ANTISPASMODIC Relax bladder and are prescribed for incontinence.

ANTICONVULSANTS Help relieve facial pain and Twitching

ANTIOXIDANT PYCNOGENOL helps cognitive problems according to Richard A Passwater, phd

AVONEX Avonex benefits are being seriously questioned by other studies. Avonex did not show any significant improvement in a recent 12 month study. It was not a blinded study, and patients were all early RRMS. (Oct 99)
Based on a retro-analysis of a two year old Phase III study they now conclude that avonex may slow brain atrophy (volume brain shrinkage) based upon a newly developed measuring test called parenchymal fraction. They claim you need to take avonex for two years of treatment before benefits are achieved. This appears to be an attempt to tie and justify their beliefs using a questionable medical stance of early and continuous use of ABC drugs.
This doesn't sound like good science to me? (November 99)

*AZATHIOPRINE  (Imuran®) protects against transplant rejection, they think it inhibits synthesis of DNA & RNA.  Studies suggest significant side effects and no benefit to MS.

BACLOFEN (Liorisal) (Basically being replaced by Tizanidine Hydrochloride) muscle relaxant for MS.  Blocks body’s pain and reflex messages to the brain.

Major down side is it leaves legs feeling weak. Other common side affects: dizziness, lightheadness, confusion, drowsiness, nausea.   If rash with itching, numbness or tingling in hands or feet, and or fainting, weakness, hallucinations, chest pain, muscle pain, pounding heartbeat stop meds call doctor right away.  Overdose causes blurred vision, blindness, difficult breathing, vomiting, drowsiness, muscle weakness, convulsion seizures.  Abrupt withdrawel may cause confusion and seizure.

CANNABINOIDS (MARIJUANA) or the active ingredient does improve Ms tremors and is a strong pain killer.  Others suggest it may be linked to stroke, systemic hypotension, impair peripheral vasomotor reflexes and alter CNS blood flow, cerebral vasculer autoregulation but solid evidence to support this belief is wanting.

*CHEMOTHERAPY MEDICATIONS used to slow disease progression.  These drugs shut down the immune system opening the patient to very serious side effects, such as cancer if predisposed.

*Azathioprine (Imuran®)

*Cyclophosphamide (Cytoxan®)

*Methotrexate

CYCLOSPORINE (Neoral and Sandimmune) protects against transplant rejection and for severe psoriasis.  It is believed to inhibit interluken II and to affect T-lymphocytes

*CYCLOPHOSPHAMIDE (Cytoxan®, Neosar® and Procytox®) used to treat cancer, severe rheumatoid arthritis, blood-vessel disease and skin disease.  Kills cancer cells, suppresses spread of cancer cells and suppresses immune system.

CYCLOSPORINE (Neoral®, Sandimmune®) an immunosuppressant that has benefits but has significant side effects especially high rate of kidney damage

DANTROLENE (Dantrium) muscle relaxant, antispastic, acts directly on muscles to prevent excess contractions. If Seizure; shortness of breath, bloody urine, chest pain, convulsions dial 911. Rash, hives; black or bloody stools; chest pain; fast heartbeat; backache; blood in urine; painful, swollen feet; chills; fever; shortness of breath, stop meds call doctor.

DONEPEZIL (Aricept) a Cholinesterase inhibitor. May improve memory reasoning and other cognitive functions in some patients. It will not reverse the disease. A drug for alzheimer’s may help with memory loss.  Did not improve verbal fluency, non-verbal memory or ability to follow conversations

IMMUNO-SUPPRESSIVE

 Immuno-suppressants MAY accelerate remyelination.

Antigen-specific immunotherapy in monkey tests suppressed the Ms symptoms but not the MRI progression. Jan 2001

MBP8298

BioMS Medical Rdmonton, Alberta has entered into Phase III clinical trials of the drug MBP8298 for the treatment for Secondary Progressive Ms.  Currently there are no effective treatment for secondary Progressive Multiple Sclerosis.

METHYLPREDNISONE (Systemic or Topical not defined) but has no effect on MS optic neurtis

*METHOTREXATE (MTX) (Amethopterin, Folex, Folex PFS, Maxate, Mexate AQ, Rheumatrix) A chemotherapy drug used to treat some forms of cancer, severe psoriasis, severe rheumatoid arthritis.  Inhibits abnormal cell reproduction.  Herbs that contain aspirin-like chemicals known as salicylates should be avoided.  These include Black cohosh - Meadowsweet - Poplar - Sweet birch - Willow - and Wintergreen.  Echinacea may produce liver toxicity.

MITOXANTRONE see (NOVANTRONE) this chemo drug suppresses the immune system and has been linked to heart problems including death.  It has been FDA approved.

MINCYCLINE an acne treatment drug appears to decrease the activity of Ms lesions in RRMs patients.  However only 10 patients were involved in the study.  Mice studies suggest improvement in mice.  Study at University of Calgary, Dr. Wee Young (2004)

NEURONTIN (GABAPENTIN) used for epileptic seizures in children and is reported effective in treating night-time leg spasms.
 

NOVANTRONE (mitoxantrone) a cytotoxic agent, a one year clinical study of RRMS on low-dose had no significant effect. It is believed to suppress certain white blood cells, T-cells, B-cells & macrophages that are thought to lead the attack on myelin sheath. Claims to significantly reduce disability progression in severely advanced Ms as a result of a two year study in Europe of 194 patients. It was given intravenously once every three months.

(2004) Novantrone was not effective in treating Primary Progressive MS.

Side affects include nausea, alopecia (hair loss), upper tract respiratory tract infection, mouth sores, urinary tract infection, menstrual disorder, transient neutropenia (reduced white blood cells) changes in cardiac rhythm, more susceptible to infection.  Requires a pregnancy test before taking the drug.

Novantrone can only be used for two years before it suddenly and mysteriously increases patients risk of dangerous heart damage, the FDA warns (Jan 2000).  WARNING:  This drug is believed to suppress the immune system and anyone predisposed to other diseases, such as cancer, may see secondary conditions escalated.  This is a high risk drug.  Caveat emptor.

Novantrone has been approved for use with worsening RRMS and ASPS by the FDA Oct, 2000.

OPTIC NEURITIS Is the swelling of optic nerve that usually clear up by themselves after 6 weeks. Drugs are not effective with this symptom.

First manifestation of 20% of MS patients.  About 50% of MS patients experience this in the form of blurred vision, decreased color perception and impaired depth perception.  It is important to note that many other diseases can cause these symptoms.
65-80% of MS with optic neuritis recover from this impairment.

Clinical trials using methyprednisome, methyprednisome followed by oral prednisone taper and a placebo after 6 months showed no difference between the treatments and no treatment.
 

ORINASE> (Sulfonylurea) an antidiabetic agent. A resident neurologist in 1980 claimed near miracle cures with this drug for is MS patients but clinical trials could not confirm his observations. This is a good reminder to proceed with caution concerning so called miracle cures for MS.

PEMOLINE (CYLERT) central nervous system stimulant but causes liver damage and is habit forming. Used on children for ADHD, attention-deficit hyperactivity. Not used with MS but ok for children??

PREDNISONE no effect on MS optic neuritis

SPASTICITY Drugs used to control spasticity.  They inhibit input from the locus ceruleus and spinal cord circuits.

STIMULANTS AND ANTIDPRESSANTS Help reduce symptoms of fatigue and depression.

TIZANIDINE - HYDROCHLORIDE 1997 Zanaflex – Tizanidine improves muscle spasticity of MS does not appear to improve muscle weakness.  Slows nerve impulses that stimulate skeletal muscles, decreasing cramping.  Breathing difficulties, heartbeat irregularities dial 911.  Fever, liver problems ( weight loss, nausea, vomiting, yellow skin or eyes) pain or burning when urinating, involuntary movements, diarrhea, vomiting, speech pain, speech problems, heartbeat irregularity, black or tarry stools, seizures, bloody vomit, fever and chills, fainting, stop meds call doctor.  Side affects can be nervousness, sensation changes (tingling, burning, prickling) skin sores, anxiety, tiredness or weakness, constipation, back pain, dizziness, dry mouth, depression, heartburn, lightheadness, muscle weakness, sore throat, runny nose, increased sweating.
 
TIZANIDINE hc1 is approved see Zanaflex below.

TREMOR (DYSMETRA & OTHER ATAXIC FEATURES) disabling tremors rarely respond to the application of medication.  Specific cause is usually not know.

TRICYCLIC ANTIDEPRESSANTS & SSRI's includes amitriptyline (Elavil® and nortriptyline (Pamelor®), SSRI's (Prozac®) (Zoloft®) and Paxil®) are used for depression and pain.  The following herbs should be avoided St. John's wort, Belladonna, Henbane, Mistletoe and Scopolia.

VALIUM (BENZODIAZEPINES DIAZEPAM) for anxiety and panic disorders, muscle spasm, alcohol withdrawal, insomnia (short term).  Affects the limbic system of brain, the part that controls emotion.  Drowsiness, weakness, tremor, stupor, coma or slow heartbeat, breathing difficulties dial 911.  Clumsiness, drowsiness, dizziness, hallucinations, confusion, depression, irritability, rash, itch, vision changes, sore throat, fever, chills stop meds call doctor.  Habit forming.

ZANAFLEX (TIZANIDINE HYDROCHLORIDE) for the management of spasticity. It reduces muscle tone without a corresponding reduction in muscle strength. It increases muscle tone by 21-37% in 82% of patients compared to Baclofen of 65% and that also causes muscle strength. Side effects include dry mouth and drowsiness.

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