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Table of Contents Introduction Types of Bipolar Disorder Diagnosis/Phases of Bipolar Disorder Page 2 Page 2 Page 3

Causes/Brain Functions of Bipolar Disease What is Depakote/What Does it Do? Facts About Depakote Other Depakote Indications Major Consequences of Depakote Conclusion

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Introduction Depakote is an FDA approved drug which is used to treat manic or mixed episodes associated with bipolar disorder, as well as certain types of seizures and migraines. Those who are diagnosed with bipolar disease, also known as manic-depressive illness, experience elevated mood swings that are often followed by episodes of depression. Bipolar disease affects about 1% of the adult population. According to studies, two-thirds of those diagnosed with the disease have
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a relative with bipolar disease or some case of depression. The exact pattern of transmission remains unknown, however the illness is known to have a strong genetic basis. Depakote (divalproex sodium) is a valproate that helps prevent those who have manic episodes associated with bipolar diseases. (1) Types of Bipolar Disorder There are four major types of bipolar disorder. An individual can be diagnosed with Bipolar I disorder, which is defined by manic or mixed episodes that last at least seven days, or by manic symptoms that are so severe that the person needs immediate hospital care. Usually, the person also has depressive episodes, typically lasting at least two weeks. Another type is Bipolar II disorder which is defined by a pattern of depressive episodes shifting back and forth with hypomanic episodes, but not full-blown manic or mixed episodes. Alternatively, an individual can be diagnosed with Bipolar Disorder Not Otherwise Specified (BP-NOS) meaning they have related symptoms of illness but may not last as long as well as not meeting diagnostic criteria for either bipolar I or II. Lastly a person can be diagnosed with Cyclothymic Disorder (Cyclothymia) which is a severe form of bipolar disorder where the person has episodes of hypomania for at least two years. (2) Diagnosis/Phases of Bipolar Disorder An individual diagnosed with bipolar disease by having the symptoms of mania (such as abnormally elevated mood, sleeplessness, racing thoughts, and pressured speech) a history of previous episodes, and a family history. A doctor could diagnose a patient with bipolar disorder solely by the presences of a manic episode even without depression occurring. These phases of manic and depression could occur daily or maybe several times a year depending on the
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individual. Episodes may occur randomly with no symptoms in between each episode. If these symptoms go untreated, these manic episodes could become more frequent and progressively more severe. The first diagnosis of the disorder typically begins in adolescence or early adulthood. (3) A phase of manic is characterized by a persistent abnormally elevated mood. (Table 1) Individuals who experience this typically have increased energy, with rapid, loud speech, a reduced need for sleep, and distractibility. Usually the manic individual will make irrational decisions and deny that they have a problem. For example, the person may make wild plans and take action on them, such as flying out the country without adequate preparation, making crazy business investments, or going on extensive shopping sprees to the point of debt. Usually following the manic episode is a depressive phase. During the depressive episode, the individual becomes tremendously sad and starts to lose interest in activities. Extreme cases may include the person having thoughts of death or suicide. The frequency and duration of episodes of mania and depression vary among individuals. Bipolar disease tends to worsen over time if not properly treated. (3)

Causes/Brain Functions of Bipolar Disease Scientists have developed research to conclude that bipolar disease has a tendency to appear in individuals whose relatives had the illness. Children with a parent or sibling who has bipolar disease are four to six times more likely to develop the illness, compared with children who do not have a family history of bipolar disease. Currently, scientists are researching what genes could possible increase a persons chance of the disease since genes are the building
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blocks of heredity. Researches are also learning that certain traits that seemed to occur in families such as, history of psychiatric hospitalization, co-occurring obsessive-compulsive disorder (OCD), age at first manic, and number and frequency of manic episodes. By continued studying of these traits, scientists are beginning to find genes that may cause bipolar disease one day. However, scientists have concluded that there is no single cause of bipolar disease and are continually researching possible causes of the disease. For example, recent image studies have shown that brains of people with bipolar disease may differ from brains of healthy people. Recent studies have shown that children with bipolar disorder have similar brain activities of those children with multi-dimensional impairment. Through studying brain differences, as well as information obtained from genetic studies, scientists are now able to better understand bipolar disorder. (4) What is Depakote/What Does it Do? Depakote (valproate semisodium) was approved by the FDA in 1995 for treating mania and preventing the recurrence of manic and depressive episodes. Divalproex sodium is a stable coordination compound comprised of sodium valproate and valproic acid in a 1:1 molar relationship and formed during the partial neutralization of valproic acid with 0.5 equivalent of sodium hydroxide. In Table 3, the chemical structure Divalproex sodium is shown. Depakote acts as a mood stablizer because it contains the active ingredient valporate semisodium. Those who have bipolar disease suffer from abnormal mood swings causing them to have high and low episodes known as mania and depression, respectively. (Table 5) Valproate semisodium works as a mood stablizer by increasing the amount of a natural calming chemical in the brain called GABA. Naturally the brain works by nerve cells sending electrical signals to communicate with eachother. In order for the brain to function properly these signals must be carefully regulated.
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Individuals with bipolar disease have abnormal eletrical signals releasing in the brain causing the brain to become over-stimulated and normal function to become disturbed. GABA is natural chemical in the brain that keeps nerve activity balance. When GABA is released in the brain it acts as a natural calming agent. Therefore those diagnosed with bipolar disease tend to have small amounts of GABA present causing the brain to become overexcited. Depakote works by preventing the breakdown of GABA in the brain thus allowing for more GABA to be present to calm nerve cells for a longer period of time. Depakote stablizies episodes of mania by inhibiting excessive firing of electrical signals ultimately calming the electrical nerve activity in the brain.(5) The machnaism behind how Depakote works is that it increases concentrations of GABA which is an inhibitory neurotransmitter. As seen in Table 6, valproate acid increases the level of glutamic acid decarboxylase (GAD), which is an enzyme responsible for the synthesis of GABA, and also inhibits the activity of the enyme responsible for the degradtion of GABA called GABA-transaminase. Therefore, by inhibitng GABA-T, more GABA will be present in the brain to stablize brain activity back towards normal levels. Also Depakote blocks voltagegated sodium ion chanels and T-type calcium channels which allows it to act as a anticonvulsant drug. (6) Facts About Depakote Depakote, also known as divalproex sodium, has been prescribed to millions of patients since 1983. Depakote and Depakote ER (extended-release) must be taken orally through tablet forms for the treatment of bipolar disease. Depakote tablets are supplied in three different dosage strengths of 125mg, 250mg, or 500mg of valproic acid depeding on your doctors recommendations.(Table 2) Patients should take the recommend initial dose of 750mg daily in divided doses. Ultimately, your doctor will tell you how much Depakote to take (how many
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tablets and what dose) and how often it should be taken. Depakote pills should be stored at room tempature. It is legally used and FDA approved for the use of those who are prescribed by doctors. Depakote should not be taken if patient has liver problems, are allergic to the ingredients, and/or the patient is preganant. Some of the unintended side affects that may occur from taking Depakote inlcude nausea, tremor, hair loss, weight gain, increased appetite, stomach pain, headache, dizziness, diaherra, blurry vision, coordination problems, double vision, sleepiness, weakness, vomiting, loss of appetite, or walking problems.(Table 4) The patient should immediately contact a doctor if any of the symptoms above occur. Any other answers to questions about Depakote could be answered at any time by the patients doctor. When it comes to the price of Depatoke, those with insurance could pay as little as $5 a month for Depkote, however those without insurance could pay up to $100 a year. Ulimately, the price varies on the dosage amount prescribed to you by your doctor. (7) Other Depakote Indications Depakote is indicated for the treatement of the manic episodes associated with bipolar diesease. The typically symptoms of bipolar disorder include pressured speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity , poor judgment, aggressiveness, and possible hostility. However, Depakote has other indications and useful in treating other conditons such as epilepsy and migraines. Patients who suffer from complex partial seizures can use Depakote as treatment by monotherapy and adjunctive therapy. As for migraines, depakote is indicated for prophylaxis of migraine headaches. Unfortunately, there is no concrete evidence that migraine headaches are treated by Depakote. (8) Conclusion

Depakote is a drug that was approved by the FDA in 1983 in order to treat bipolar disorder along with other symptoms such as epilepsy and migraines. Bipolar disorder is a very rare but serious disease that affects only about 1% of Americans. Through research, Depakote has been seen has a top brand drug to help minimize the negative and harmful effects of individuals with bipolar disorder.

Table 1. Signs and Symptoms of Manic and Depressive Episodes

Manic episodes Increased energyEuphoric feelingsAgitationLess need for sleepInflated beliefs in abilitiesPoor judgmentIncreased sex driveDenial that problem exists
Table 2. Picture of the Depakote Tablets

Depressive episodes Sad or empty moodLoss of interest in normal activitiesFeelings of guilt, worthlessness, or hopelessnessDifficulty concentratingRestlessness or irritabilitySleep disturbances (can be too much or too little)Changes in appetiteThoughts of death or suicide

This is a picture of what the Depakote pills look like. Table 3. Chemical structure of Depakote

This is a picture of Depakotes chemical structure.

Table 4. List of Side Effects

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect. Disturbances of the gut such as diarrhoea, nausea, vomiting or abdominal pain. Increased appetite and weight gain. Decrease in the number of platelets in the blood (thrombocytopenia). Temporary hair loss - regrowth may be curly. Increased alertness. Aggression. Hyperactivity.

Shaky movements and unsteady walk (ataxia). Tremor. Inflammation of blood vessels (vasculitis). Drowsiness. Confusion. Liver disorders. Irregular or stopping of menstrual periods. Skin rashes. Decreased numbers of white blood cells in the blood (leucopenia). Anaemia. Acne. Increased hair growth (hirsutism). http://www.netdoctor.co.uk/depression/medicines/depakote.html#ixzz2n0bNZq00

This is a full list of all the possible side effects that could affect a person will they are taking Depakote. Table 5. Scale of Moods

This picture shows a scale of how people diagnosed with bipolar disorder can switch back and forth from mania episode to a depression stage. In the middle of the scale is where normal moods would occur and this picture gives a great example of how a person with bipolar disorder can vary in moods.

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Table 6. Pathways of Valproic Acid

This diagram above shows the Pathway of Depakote when it is inside the body. Valproic acid increases the amount of gamma amino butyrate (GABA) levels in the brain as well as blocking voltage gated ion channels. GABA is formed from alpha-ketoglutarate through the TCa cycle and metablozied to succinare semiadehyde by GABA transaminase. GABA-T is an enzyme responsible

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for breaking down GABA so by inhibiting GABA-T more GABA will available to stabilize brain activity.

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Citations (1) "Bipolar Disorder." Pdrhealth. Physicians Desk Reference, n.d. Web. 09 Dec. 2013. <http://www.pdrhealth.com/diseases/bipolar-disorder>. (2) "Bipolar Disorder." NIMH RSS. National Institute of Mental Health, 2008. Web. 09 Dec. 2013. <http://www.nimh.nih.gov/health/publications/bipolar-disorder/index.shtml>. (3) "Bipolar Disorder-Diagnosis." Pdrhealth. Physicians Desk Reference, n.d. Web. 09 Dec. 2013. <http://www.pdrhealth.com/diseases/bipolar-disorder>. (4) "Bipolar Disorder." NIMH RSS. National Institute of Mental Health, 2008. Web. 09 Dec. 2013. <http://www.nimh.nih.gov/health/publications/bipolar-disorder/index.shtml>. (5) "Depakote (valproate Semisodium)." Netdoctor. Netdoctor, 03 Sept. 2011. Web. 09 Dec. 2013. <http://www.netdoctor.co.uk/depression/medicines/depakote.html>. (6) "DrugBank: Valproic Acid (DB00313)." DrugBank: Valproic Acid (DB00313). Drug Bank, n.d. Web. 09 Dec. 2013. <http://www.drugbank.ca/drugs/DB00313>. (7) "Stay on Trackwith Depakote." Depakote (divalproex Sodium). N.p., n.d. Web. 09 Dec. 2013. <http://www.depakote.com/>. (8) "Depakote (Divalproex Sodium Delayed Release Tablets) Drug Information: Indications, Dosage and How Supplied - Prescribing Information at RxList." RxList. N.p., n.d. Web. 09 Dec. 2013. <http://www.rxlist.com/depakote-drug/indications-dosage.htm>
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