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Biology 103
2005 Second Paper
On Serendip

A Cure Which Offers Even More Grief? : The Use of Lithium as a Treatment for Bipolar I Disorder

Lizzy de Vries

To her classmates, teachers, and friends, Allison* was a thirteen-year-old who everyone admired and wanted to be like. Unlike most young adolescents, she seemed to effortlessly balance an active social-life, honors level academics and demanding extra-curricular activities. She was an accomplished violinist and had a strong relationship with her family. Mid-way through the eighth grade, Allison's personality began to change drastically. Her grades dropped and her interests in socializing and in music declined. Many evenings her parents found her lying in bed staring at a wall. She answered questions with only one word, and later admitted that it just felt like it took too much effort to speak in full sentences. Three months before her fourteenth birthday, Allison made a feeble attempt at committing suicide. The next day she was diagnosed with Major Depression and put on a high dosage of anti-depressants.

Over the course of the following month, Allison began to feel happier than she ever had in her life. Her confidence was so high that it seemed absurd to others, and sometimes to herself. She now confesses that she felt so powerful that she once crossed a busy two way street in traffic, never looking either way. Her mind told her that there was no way a car could possibly hit her. Allison loved the extreme euphoria she was experiencing, but it was clear to her parents and doctors that her emotions were not normal. She was re-diagnosed with Bipolar I Disorder.

Bipolar I Disorder is a complex and severe mental illness. Patients suffer from periodic episodes of depression and mania, typified by inflated self-esteem, hyperactivity and reckless or impulsive behavior. If Bipolar I is not treated, it has an approximately 15% risk of death by suicide. Shockingly, the disorder is the third leading cause of death among people aged 15-24, and the sixth leading cause of disability for people aged 15-44 years. It is a lifelong disease with both genetic and environmental factors of causation. Some illnesses such as multiple sclerosis and hyperthyroidism can cause mania. As in the case of Allison, antidepressant medication can also trigger mania. Manic episodes usually last for between two weeks and five months, while depression can last up to a year or more. (4)

When Allison was diagnosed with Bipolar I Disorder, her psychologist put her on Eskalith, a form of Lithium, the medication prescribed most often to treat Bipolar Disorder. It evens out mood swings and usually reduces manic symptoms in one or two weeks. (3) Lithium, an alkali salt, was discovered in 1817, and in the late 1800's doctors using it to treat gout began to hypothesize that it might have mood stabilizing properties as well. In 1949, Australian psychiatrist John Cade published the first paper on the use of lithium as a remedy for acute mania, and the U.S. Food and Drug Administration approved lithium for us in 1970. It was not until 1998, however, that scientists began to have any idea of how or why it worked. Researchers at the University of Wisconsin found that lithium acts on receptors for the neurotransmitter glutamate. Too much glutamate in the space between neurons causes mania, and too little causes depression. Lithium keeps the glutamate level at a stable level. (8) Another hypothesis proposes that lithium alters membrane excitability by partially replacing sodium, and yet another theory says that it manages calcium levels, which have been found to be low in depressed individuals and high in people experiencing mania. (1)

While lithium has been established as the primary pharmaceutical treatment for Bipolar I Disorder, in many cases it has been found to cause as much harm as it does good. Initially, patients taking lithium can experience side effects such as drowsiness, weakness, nausea, fatigue, increased thirst and urination, and hand tremor. (3) Allison was particularly distressed by the tremor. She was embarrassed that it was difficult for her to bring a soup spoon to her mouth, and holding her violin and bow became increasingly difficult. Researchers have found a wide range of occurrence of lithium tremor, 4% to 65%. (2) On an About.com message board for individuals with Bipolar I, some complained of excessive hair loss and even memory loss. "I have lost memory for periods of time of an hour or more completely. I have no recollection of conversations I was involved in during these times, or even places I've been to during these times. I have even zoned out so badly that I have 'woken up' out of my daze, sitting in a parking lot somewhere, not knowing how I got there or how long I had been there. It's truly frightening..." (9)

Lithium has also been proven to cause weight gain. This may be due to lithium-induced hypothyroidism, which slows down the metabolism, or increased thirst which leads people to drink high-calorie fluids. In a 1999 study, researchers found that a molecular receptor known as 5-HT1B is a "target" for lithium. 5-HT1B are controllers of the system that distributes serotonin, a neurotransmitter affecting depression and appetite. One post on About.com stated "Gained 75 lbs. since I began lithium. I have always been petite now 200+. I am 5'3" and was a marathon and long-distance runner. You ask, "why doesn't she just go out and run?"...duh, lithium is sedating. In me it causes a "nothing really matters any more, I'll just sit in my chair for a week and veg-out" attitude. Gaining weight has caused me to feel humiliated, painful physically, caused isolation because of shame." (9)

Allison experienced an atypical side-effect of lithium. In her senior year of high-school, after four years taking a combination of lithium and anti-depressants, she began to experience shortness of breath and a racing heart beat. She had a consistent blood pressure of at least 140 over 100, extremely high for a young girl in good physical health and condition. After many tests, it was determined that Allison was experiencing hypertension, however, it could not be determined why. She increased her exercise and went on a very low-sodium diet, but it wasn't until she was taken off lithium and put on another mood-stabilizer, Depakote, that her blood pressure returned to a perfectly normal 120 over 80. There is no scientific proof that lithium can cause high-blood pressure, and psychiatrists say that what Allison went through was extremely rare. But as is the case for many Bipolar I patients, being on lithium made Allison's quality of life even worse than it already had been for a young girl dealing with a difficult disorder.

For children and adults, Bipolar I is an extremely confusing and grueling disorder. Patients and their families and friends alike find it very difficult to understand why individuals with Bipolar I are the way they are, and relationships are often negatively affected. It seems to me that it is a horrific reality that the primary treatment for this disorder can cause patients so much grief. Hopefully, the psychiatric and scientific community will continue to endeavor to discover more beneficial medications so that those who already suffer mentally do not have to endure physical issues as well. I was pleased to read that Tamoxifen, an anti-estrogen drug used as a preventative measure for women at high-risk for breast cancer, is currently being studied as a possible treatment for mania. Tamoxifen is an inhibitor for protein kinase C, a signaling pathway within nerve cells which has been found to have some involvement in Bipolar Disorder. (10) I am optimistic that one day, doctors will be able to offer patients true freedom from the hardships which I suppose only those who have experienced mania and depression can truly comprehend.

*Allison is a real person who I am well-acquainted with. Her name has been changed.

WWW Sources
1)Biological Theories of Manic-Depression, on the Serendip website
2) Gelenberg, A.J. "Lithium Tremor." J Clinical Psychiatry, Vol. 56 (1995), pp 283-7
3)Medications for Bipolar Disorder , on the About.com website
4)Bipolar I Disorder, on the Internet Mental Health website
5)The Antisuicidal Effects of Lithium, on the McLean Hospital Psychiatric Update website
6)Lithium, on the MHRA website
7)Medications, on the National Institute of Mental Health website
8)Lithium: The First Mood Stabilizer, on the About.com website
9)Speaking From Experience: Lithium, on the About.com website
10)Tamoxifen Serendipity for Bipolar Disorder?, on the About.com website



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