Phenytoin / Epanutin / Dilantin – Promotes Well-Being while acting as a Prevention Therapy

Epanutin belongs to a class of drugs known as ‘anticonvulsants’ and as such is approved throughout the world for the treatment of certain types of epilepsy such as:

Generalised tonic-clonic seizures (grand mal epilepsy)

Temporal lobe epilepsy

It is also use to treat other convulsive states such as seizures associated with brain surgery or head injury. Epanutin is more commonly known as a Dilantin, and contains the active ingredient phenytoin.

However, Epanutin has a myriad of what are referred to as “off-label” uses i.e. where regulations allow for approved medications to be prescribed for uses other than their intended indications. Indeed, medications containing the active ingredient phenytoin possibly have the highest number of off-label uses of any drug in the United States, where its only official approved use by the FDA (Food and Drug Administration) is still just that of an anticonvulsant.

But before we look at these off- label uses in more detail, it’s important to first look at Epanutin’s use as an anticonvulsant because this is the activity for which it is approved and most well known.

Epanutin and Seizures

Epanutin works by stabilising electrical activity in the brain which, if disturbed, can result in fits or seizures. Electrical activity is one of the key ways in which brain and nerve cells communicate with one another. Neurons (the cells that make up the brain, skeletal and nervous systems) use electrical and chemical signals to either communicate with each other or to communicate with muscle cells. The points at which electrical signals are converted into chemical signals and then back into electrical signals are called synapses.

In order for the brain and nervous system to function properly, these electrical signals must be carefully regulated. If abnormally rapid and repetitive electrical signals are released in the brain, the brain becomes over-stimulated and normal function is disturbed. This can result in fits or seizures.

By preventing excessive electrical activity in the brain, Epanutin stops seizures. Just how exactly Epanutin prevents this excessive electrical activity is not fully understood. However, it is known that nerve cells require a build up of sodium if an electrical signal is to be charged and passed on to other nerve cells. Epanutin is thought to work by preventing sodium from entering nerve cells when they begin to fire rapid and repetitive electrical signals. This stops any build up of sodium inside nerve cells. Without the necessary build up of sodium, electrical signals cannot be built up and passed on which results in a stabilization of the brain’s electrical activity.

Jack Dreyfus and Epanutin

As mentioned above, Epanutin, like so many other medicines, is used to treat a whole host of other conditions beyond the specific use it has been approved for. Medicines based on phenytoin as their active ingredient are not new. Phenytoin was first invented in 1908. However, it was not until its patent expired in 1963, that the drug’s real value in treating conditions other than epilepsy was truly discovered. Over the years, millions of people have been prescribed phenytoin and literally thousands of research papers have been written about it and its use in treating a whole range of conditions.

Much of the work into phenytoin has been spearheaded by the Dreyfus Medical Foundation. The Dreyfus Medical Foundation was established by the Wall Street trader Jack Dreyfus. During the late 1950s this hugely successful, high achieving man was confronted by possibly one of the greatest challenges of his life – severe depression. For six days a week for over 5 years, Dreyfus consulted with his doctor but remained plagued by his illness.

Dreyfus became convinced that his depression was in fact due to inappropriate electrical activity within his body as a result of which he persuaded his doctor to prescribe him phenytoin. Much to everyone’s surprise and relief, the phenytoin very quickly returned Dreyfus to good health. Dreyfus asked for six other people with similar symptoms to be treated in the same way and again they all recovered.

Feeling obligated to investigate further, Dreyfus then took the somewhat unusual step of retiring from his highly successful business life and, using his own money, established the Dreyfus Medical Foundation. The Dreyfus Medical Foundation operates as a charitable medical foundation, designed specifically to collate global information on phenytoin, to educate the public as to the benefits and other uses of phenytoin and to try and persuade the FDA to change their narrow listing of phenytoin as an anticonvulsant. For those interested, Dreyfus has written two books detailing his life and his work in relation to phenytoin – “The Story of a Remarkable Medicine” and “Written in Frustration”.

As a testament to the many benefits of phenytoin, Jack Dreyfus lived to the age of 95, passing away peacefully in March 2009.

Why can Epanutin be used for numerous conditions in addition to the treatment of epilepsy?

The reason that phenytoin can be used to treat such a diverse range of conditions is down to the number of pharmacologic effects it has in addition to its anticonvulsant capabilities. Phenytoin has a number of distinctive characteristics which, when viewed together, set it apart from other substances. These characteristics include:
1. Regulation of bioelectrical activity at the level of the individual cell membrane. Most cellular activity is modulated by the electrical and electrochemical processes that occur on cell membranes, making this a level that is fundamental to all body functions. This, perhaps, helps to explain why the therapeutic effects of phenytoin can be felt across such a wide range of disorders.
2. Correction of inappropriate electrical activity without interfering with normal electrical function
3. Regulatory effects on endocrine and metabolic processes and on stress
4. The ability to help healing
5. The ability to exert a calming effect without being a sedative and yet it can also exert an energising effect without being a stimulant

In addition, the effects of phenytoin are known to be felt quickly – when taken orally it is effective within an hour – and it is not a habit forming medication.

What else is Epanutin used to treat?

According to the Dreyfus Foundation, phenytoin is effective in treating over eighty different symptoms and disorders and is currently being used for a wide variety of conditions in nearly thirty countries worldwide. The conditions that respond to phenytoin therapy include:

Pain

Cardiovascular Diseases

Neuromuscular Disorders

Thought, Mood and Behaviour Disorders

Stress

Poor Concentration and Learning

Sleep and Jet Lag

Pain including the treatment of trigeminal neuralgia

Because phenytoin is capable of treating so many different types of pain, it is useful as a non-habit forming general pain medication treatment that does not possess sedative effects. Furthermore, phenytoin can be used as a standalone treatment or in combination with other pain medications. It appears to be particularly useful in treating conditions such as migraine and other types of headache; post-operative pain and post-stroke pain; pain caused by skeletal muscle spasms; pain associated with malignant disease and phantom limb pain.

Repeated episodes of severe pain in the tongue, throat, ear and tonsils (glossopharyngeal neuralgia) and repeated episodes of severe pain but this time in the lips, gums, cheeks, chin or eyes (trigeminal neuralgia) respond particularly well to phenytoin therapy. As such phenytoin is very commonly used to treat these conditions. In the case of trigeminal neuralgia, facial nerves spontaneously send messages of pain to the brain. Phenytoin prevents the nerve signals being sent inappropriately and, by doing this, relieves the pain. However, it is recommended that phenytoin should only be used as second line therapy for this condition, in people who cannot take another medicine called carbamazepine, or for people in whom carbamazepine is ineffective.

Cardiovascular Conditions

Phenytoin is known to be useful in the treatment of a wide range of cardiovascular disorders, for example:

Phenytoin can be used to treat a variety of cardiac arrhythmias

In clinical situations, phenytoin has been reported to reduce the frequency and severity of angina attacks.

Phenytoin has been shown to decrease sympathetic nervous system activity. This, in turn, acts to reduce cardiac contractile force, blood pressure and heart rate. Phenytoin has, therefore, been reported to be useful in treating hypertension (high blood pressure).

Phenytoin has been shown to have beneficial effects on the cardiac conduction system e.g. it has been found beneficial in the treatment of the prolonged Q-T interval syndrome.

Reports have demonstrated that phenytoin can act to increase HDL cholesterol levels. HDL cholesterol is sometimes referred to as “good cholesterol” because of the inverse relationship between HDL cholesterol levels and atherosclerotic problems such as myocardial infarction (heart attack) and stroke. It has therefore been suggested that phenytoin might help as a preventative measure against such disorders

Neuromuscular Disorders

Phenytoin acts in muscle in a similar way to the way it acts in nerves, that is to say it corrects inappropriate electrical activity without interfering with normal function. This action means that it may be effective in helping to treat neuromuscular disorders such as restless legs syndrome, Sydenham’s chorea, the abnormal movements associated with Parkinson’s Disease, muscle spasms, and continuous muscle fiber activity syndromes such as neuromyotonia (Issacs’ syndrome) and myotonic dystrophy. Even intractable hiccups have been observed in the clinical environment to respond to phenytoin therapy.

Thought, mood and behaviour Disorders

With its ability to calm an overbusy brain, phenytoin is well placed to treat those suffering from a whole range of thought, mood and behaviour disorders. Indeed, for many years those treating epileptics with phenytoin noted positive side benefits of the treatment including improvements in emotional stability, mood, memory and cooperativeness (see Goodman and Gilman 19551).

An overactive brain can result in a number of mentally distressing conditions with symptoms such as preoccupation, multiple thinking, and flashes and fragments of thoughts coming and going. By reducing uncontrolled electrical activity in the brain that causes such symptoms, phenytoin can quickly restore more normal thinking processes without any sedating effects (usually within the hour). As can be clearly demonstrated by the experiences of Jack Dreyfus when treating his depression, phenytoin can provide quick and effective relief.

What is more phenytoin appears to be effective when dealing with extremes of mood ranging from hyperexcitability through to the lethargy that often comes with depression. Even though these two extremes appear entirely disparate, phenytoin is capable of calming the overexcited individual as well as restoring the lethargic, listless person to normal energy levels. This makes phenytoin a potentially useful candidate in the treatment regime of certain psychiatric disorders such as bipolar disorder although a note of caution should be sounded as phenytoin can interact with a number of medicines often used in the treatment of such illnesses.

Overactive brains also often produce feelings of fear and anger and here again phenytoin can be especially helpful. Anger can result in impatience, implusiveness, irritability, aggression, hostility, rage, and violence, whereas fear can manifest itself as such things as worry, anxiety, guilt, pessimism and depression. Phenytoin therapy appears to have a normalising effect, reducing states of excessive anger or fear. Indeed, in one study carried out with prison inmates and institutionalized juvenile delinquents, phenytoin therapy was shown to decrease violent behaviour. (Dreyfus 19812).

Stress Reduction

Phenytoin also acts to regulate the hypothalamus-pituitary-adrenal axis (the HPA axis) which acts as the body’s neurohormonal regulator of stress responses. By doing this, it can help to decrease levels of excessive chemicals closely related to stress namely epinephrine, norepinephrine and cortisol. The effects of too much cortisol can be particularly damaging. For example, cortisol can weaken the immune system, it can act to lower bone formation which may ultimately result in the development of osteoporosis, it can increase blood pressure and prolonged cortisol secretion can cause hyperglycemia (high blood sugar). Therefore, being stressed for long periods can be very detrimental to our health. Unfortunately, not only do cortisol levels rise when we are stressed but they also increase with age.

Improving Intelligence, Concentration and Learning

Research has demonstrated that phenytoin is capable of increasing intelligence, concentration, and learning. For example, measurable increases in the results of IQ tests and improvements in long term memory, concentration and verbal performance were found in both young and old healthy volunteers who took part in double blind, placebo controlled studies carried out in the US. The subjects who participated in these trials achieved these results by taking 100mg of a medication containing phenytoin twice a day (Smith 19723, 19754).

Sleep and Jet Lag

Phenytoin has been shown to help people who suffer from insomnia, sleep disturbances and jet lag. Over active brains are known to cause sleep problems. People with over active brains often have difficulty in getting to sleep or may sleep lightly and suffer from unpleasant dreams and nightmares. This results in too little sleep which can severely impact a person’s ability to cope with even the most routine of day to day tasks as well as having a significant impact on their health. Other people may have sleep problems in that they sleep for excessively long periods of time (sometimes referred to as avoidance sleep). Phenytoin can help to quickly correct these sleep disturbances and can also help to overcome the sleep disturbances associated with jetlag. Stamina is also improved.

Other Conditions

Given that it is estimated that medications with the active ingredient phenytoin can be used to treat over 80 different conditions, it’s not possible to examine them all in detail in this article. Some of the other conditions that it is known to be helpful in the treatment of include:

Severe pre-eclampsia

Some skin diseases such as recessive dystrophic epidermolysis bullosa and junctional epidermolysis bullosa

Aids

Rheumatoid Arthritis

Binge Eating

Bed Wetting

Drug addiction and alcoholism

What’s more, because of phenytoin’s ability to calm an overbusy brain and to improve sleep both in quality and duration, taking phenytoin will leave you feeling better and enhance feelings of well being. Add to this it’s abilities to physically improve your health such as increasing HDL levels and lowering blood pressure and it’s clear that not only is phenytoin useful in treating illnesses once they are established but is also an important preventative therapy as well.

Dosage

For epilepsy, the average dose for adults and children over six is 100mg usually taken three times a day before meals. If an additional 100mg dose is required, it should be taken before bedtime. For children aged between four and six years the initial dose should 100 mg twice daily. For younger children and nursing mothers, the initial dose is 50mg twice daily. Total adult dosage should not exceed 600mg.

As an anti-aging medicine, doses of 25mg to 50mg daily are considered more than sufficient.

Doses should be taken with at least half a glass of water.

Side effects

Extensive and intensive use over many decades has helped to establish the parameters of safety for phenytoin (Epanutin). As with all medications, there is a risk that Epanutin may cause side effects. Remember though you might not experience any side effects at all and if you do it is unlikely that you will suffer from all the side effects listed below.

Side effects may include:

Central Nervous System side effects; Periodic, rhythmic ocular oscillation of the eyes (Nystagmus-Ataxia), slurring and speech alterations, mental confusion, dizziness, insomnia, temporary nervousness and headaches. The effects will most likely disappear with continued use of the product, although a weaker dose is recommended.

Possible nausea, vomiting and constipation; Taking Epanutin during or immediately after meals may help to prevent gastrointestinal symptoms.

Skin Rash - in children and young adults this may appear as a red rash not unlike a measles rash or scarlet fever rash.

Hematological alterations may occur such as thrombocytopenia (a deficiency in the number of platelets circulating in the blood), leucopenia (a decrease in the number of white blood cells found in the blood), granulcytosis (an increase of the number of granulocytes in the blood), agranulcytosis (a decrease in the number of granulocytes in the blood) and pancytopenia (a deficiency in all types of blood cells).

Gingival hyperplasia (overgrowth of gum tissue) - good oral hygiene, including gum massage, frequent cleaning and proper dental care may help to avoid this side effect.

Caution and Warnings

Epanutin should be used with caution in the elderly. Caution should also be exercised by people with the following conditions:

Decreased liver function

High levels of urea in the blood (uraemia)

Hereditary blood disorders called porphyrias

People who consume large amounts of alcohol

Diabetes

Epanutin is not recommended for patients with a history of hypersensitivity to hydantoins. Epanutin contains lactose. Although the amount of lactose in Epanutin is probably not sufficient to cause intolerance symptoms, cases have been reported of poor tolerance to this product in children and adolescents. Consult a doctor in the case of diarrhoea.

Do not suddenly stop taking Epanutin unless your doctor tells you otherwise, as suddenly stopping treatment is likely to make your symptoms return. If this medicine is stopped, it should normally be done gradually, under the supervision of your doctor.

Phenytoin can interfere with the way the body metabolises vitamin D. If you don't get enough vitamin D from your diet or from exposure to sunlight, this could cause bone pain, fractures, or a disease called ricketts. Ask your health care professional for more information.

Phenytoin decreases the blood levels of hormonal contraceptives that contain oestrogen and/or progesterone. This can make these types of contraceptive ineffective, or cause breakthrough bleeding. If you need oral contraception while taking phenytoin, you should be prescribed hormonal contraceptives that contain a total of at least 50 micrograms of ethinylestradiol (oestrogen), or use non-hormonal methods of contraception, such as condoms.

It is important for women who could get pregnant to discuss contraception and pregnancy with their doctor before starting treatment with this medicine (for pregnancy see further information below).

Phenytoin may increase the anti-blood-clotting effect of the anticoagulant medicine warfarin. If you are taking phenytoin in combination with warfarin your blood clotting time (INR) should be regularly monitored, particularly when starting or stopping treatment and after any dose changes.

Epanutin is not available for shipment to the UK or EU.

Pregnant Women and Nursing Mothers

Because the safety of this product during pregnancy has not been proven, its use by pregnant women should be assessed not only according to the benefits involved to the mother, but also to the possible danger to the foetus. Recent studies suggest a 4% risk of birth defects in new-borns (approximately double that of the general population) where the mother receives treatment for epilepsy during pregnancy.

Given this increased risk, the following guidelines are recommended:

Plan your pregnancies with the help of your specialist

If you are already pregnant, do not interrupt treatment and consult your neurologist

If you are breast-feeding, consult your paediatrician

Drug Interactions

Epanutin should not be taken with barbiturates, coumarinic anticoagulants, Disulfiram, Phenylbutazone and Sulphaphenazol, Isoniazid, tricyclic antidepressants, Methopyrone and theophilline derivatives.

References

1. Goodman , L. S. and Gilman, A. The Pharmacological Basis of Therapeutics, 2nd Ed., 181-188, Macmillan, New York, 1955
2. Dreyfus, J. A Remarkable Medicine Has Been Overlooked. New York: Simon and Schuster, 1981
3. Smith, W., Lowry, J. The Effects of Diphenylhydantoin on Cognitive Functions in Man. Drugs, Development and Cerebral Function. Springfield, IL: Charles C. Thomas, 1972, pp. 344 351
4. Smith, W., Lowry, J. Effects of Diphenylhydantoin on Mental Abilities in the Elderly. Journal of the American Geriatric Society. 1975, Vol. 23, 5, pp. 207 11