Is Lithium a Salvation for Bipolar Disorder
Bipolar disorder is a debilitating mental illness that causes extreme fluctuation in mood. One day, a patient may be manic, full of energy, then depressed to the point that the patient won’t leave their bed for days. These symptoms, extreme and unpredictable in nature, require constant medication and supervision. The main drug used in treating bipolar disorder is lithium. Through the years, lithium has been studied on how it affects patients genetically and chemically along with potential side effects. From researching how lithium affects the human body, it will be seen if the mood stabilizing effects of lithium are more valuable to the treatment of bipolar disorder patients over the possibility of side effects.
Today, lithium is the foremost treatment for bipolar disorder, but when did doctors figure out that lithium was an effective mood stabilizer? The earliest recorded use of lithium or specifically lithium bromide was in 1870 by neurologist Silas Weir Mitchell who prescribed it as an anticonvulsant and a hypnotic, but it was not until 1871 that lithium was specifically used to treat mania. It was “William Hammond, professor of Diseases of the Mind and Nervous System at the Bellevue Hospital Medical College in New York, became the first physician to prescribe lithium for mania” (Shorter). Later in 1894 in Denmark, psychiatrist Frederik Lange used lithium carbonate to treat melancholic depression in thirty-five of his patients with positive results. However, after 1894, Lange’s research was forgotten about and the mainstream use of lithium disappeared. “In the first half of the 20th century there are virtually no references to lithium in the psychiatric literature, although a tradition of lithium treatment does seem to have persisted.” (Shorter) and it wasn’t until 1949 when the use of lithium was revived. In 1949 in Melbourne, Australia, John Cade treated ten of his manic patients with lithium citrate and lithium carbonate. Cade’s patients “..responded remarkably well, becoming essentially normal and capable of discharge after years of illness.” (Shorter), but also in 1949 lithium chloride was used in “a failed experiment..as a substitute for sodium chloride in patients with congestive heart failure” (Shorter) causing lithium to once again fall into obscurity. Three years later in 1952, lithium started to be recognized by the psychiatric community when Mogens Schou, a psychiatrist at Aarhus University psychiatric clinic, started treating patients with lithium in random drug trials. Shou, after finding positive results on lithium, published his results in a British journal. From that point on, lithium’s use as an effective mood stabilizer spread throughout the world with lithium being officially registered as “..lithium gluconate in 1961 in France, lithium carbonate in 1966 in the United Kingdom, lithium acetate in 1967 in Germany, and lithium glutamate in 1970 in Italy” (Shorter). The United States registered lithium as an FDA-approved drug in 1970 and became the fiftieth country to do so. From historical records, lithium has been shown to be effective in treating bipolar disorder, and from technological innovations, doctors are now able to see from a chemical level how lithium works in treating mania in bipolar patients.
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From the background provided it was shown that lithium has been proven effective over the past one hundred and forty-six years within the psychiatric field, and now with current technology doctors have begun to try and figure out how lithium works within the human body. The exact detail of how lithium regulates mood within the brain is a mystery, especially since the human brain still remains mysterious to doctors. However, after much research, the medical community has a basic understanding of how lithium helps a bipolar patient. Lithium acts on a patient’s nervous system, the spinal cord, and the brain. Within the brain, lithium increases “…neuroprotective factors BDNF and BCl-2 and decreases apoptotic (cell death factors) BAX and P53” (Post). This means that lithium increases brain function by signaling the increase of the proteins BDNF and BCI-2, which promote nervous tissue and stem cell growth, and the decrease of the proteins BAX and P53 which control cell death. Also, in recent studies, it has been found “that the mechanism of manic depression may be related to a growth factor deficiency rather than a neurotransmitter imbalance” (Young). This quote explains why increased brain function and growth, stimulated by lithium, helps bipolar patient since their brain is lacking in proteins that promote nervous tissue and stem cell growth. This increase in brain function from lithium brings about other benefits (which have been proven in scientific studies) such as the prevention of depression, reducing the risk of dementia, and enhancing the efficiency of other psychotropic drugs (Post). From a chemical viewpoint, lithium is quite effective in treating and regulating a bipolar patient’s mood along with added benefits. However, once the chemical interaction with lithium was understood, doctors began to look at how lithium might affect a patient’s genes.
After years of medical research and innovations, doctors are not close to finding a cure for mental illnesses such as bipolar disorder. However, through the use of lithium, doctors have found genetic breadcrumbs that may be the key to what causes bipolar disorder. Bipolar disorder “..is highly heterogeneous in terms of symptoms and treatment efficacy. Factors shown to lead to disease susceptibility are varied and could be both environmental and genetic” (Cruceanu) which means that bipolar disorder symptoms, possible causes, and treatment are unique to each patient which makes treatment much more difficult. From research and records of lithium treatment, doctors have found that a certain type of patient responds well to the treatment of lithium. These patients have several factors in common which are “episodic course of illness, low rates of co-morbid conditions, absence of rapid cycling, and a family history of BD” (Cruceanu). This quote means this type of patient has a family history of bipolar disorder, no other mental illnesses, and clearly defined episodes of mania or depression. This type of patient also makes up the majority of bipolar disorder patients. From this majority, doctors began to study how lithium affects patients on a genetic level in the hopes of finding the exact gene where bipolar disorder comes from. From scientific studies, doctors have found “..a positive association with the gene for phospholipase Cy1… Phospholipase C is a promising candidate gene because of its role in the phosphoinositol cycle, a major target of lithium” (Lerer). Phospholipase Cy1 is a gene that controls the phosphoinositol cycle, and this cycle creates lipids that strengthen all of the cells found in the human body and keep them healthy. Without the correct number of these lipids, cells (possibly the ones that make up the brain) do not do their job. In theory, the deterioration or abnormal growth of the gene phospholipase Cy1, which lithium directly affects by stimulating brain and nervous tissue growth, could be the possible cause of bipolar disorder itself. Through the use of lithium, doctors have not only found an effective mood stabilizer but also the possible key to the cause of bipolar disorder itself. However, lithium is still a man-made drug and all drugs have side effects.
The biggest concern for any doctor or patient is the possible side effects of a drug. Lithium is an effective mood stabilizer, but it can have some toxic side effects. The main side effect that concerns patients is the possibility of “..deterioration in renal function evidenced by increasing creatinine levels and decreases in glomerular filtration rate” (Post). Within the body, the kidneys maintain the creatinine level (creatinine is a waste molecule made from muscle metabolism) by disposing of it through urine. If the creatinine level is too high in a patient, then that indicates that the kidneys are failing because of the use of lithium. This side effect, while life-threatening, is easily managed through the “Use of minimum effective doses and careful monitoring is typically recommended.” (Post). Also, so far “..no patient went on to end-stage renal failure requiring dialysis” (Post) which shows that this side effect is easily contained by maintaining the proper dosage of lithium and monitoring a patient’s creatinine level. Other possible side effects of lithium are “.. diarrhea, tremor, creatinine increase, polyuria/polydipsia/diabetes insipidus, and weight gain” (Ohlund) which, again, can also be contained through the proper and correct dosage of lithium depending on each individual patient. Side effects of lithium can be toxic, but by doctors carefully monitoring and prescribing the correct dosage, the benefits of lithium far outweigh the side effects.
It has been shown from a chemical and genetic level that lithium is an effective treatment for bipolar disorder with side effects that can be safely contained through the monitoring of dosage. However, there is the possibility that lithium could be replaced by another drug and there is still a minority of patients that do not respond well to lithium. Earlier, it was shown that patients that respond best to lithium have a family history of bipolar disorder, no other mental illnesses, and clearly defined episodes of mania or depression. This seems like a very particular type of patient, but there are “four basic types of bipolar disorder” (NIMH) and the description above describes bipolar I disorder patients. Bipolar I disorder patients make up the majority of bipolar patients, so the use of lithium is effective for most patients. For patients of bipolar II disorder and the other two categories where the patient does not “..meet the diagnostic requirements for a hypomanic episode and a depressive episode.” (NIMH) lithium is less effective. The other three categories of bipolar disorder are bipolar II disorder, cyclothymic disorder, and unspecified bipolar disorder. These patients have no family history of bipolar disorder and may have other mental illnesses such as schizophrenia that possibly present stronger than their bipolar disorder symptoms. For patients of these other three categories, lithium is a less effective treatment. However, lithium still has a mood-stabilizing effect on the patient. This is where emerging drug treatments for bipolar disorder may help the minority of bipolar disorder patients. In a “..trial patients were originally treated with lithium for at least one month before having riluzole added to their regimen. The authors noted a significant improvement in depressive symptoms but only 8 subjects were able to complete the 8-week trial.” (Brady) This shows that combining lithium and riluzole for abnormal bipolar patients could improve their depressive symptoms. Another drug is tamoxifen which reduces manic symptoms and “Tamoxifen did have a significant additive effect when combined with lithium” (Brady), so, again, lithium boosts another drug's effectiveness that may be lacking without lithium. There are new treatments for bipolar disorder being discovered and tested every year, but “..lithium is still recognized as the most effective prophylactic agent for BD. Moreover, continued treatment with lithium has been associated with a significantly reduced risk of suicide in patients with mood disorders” (Cruceanu). Lithium is the foundation for the treatment of bipolar disorder and until a drug is discovered that is more effective in multiple ways over lithium than lithium will not be replaced anytime soon.
Lithium has been proven to be quite effective in treating bipolar disorder. From a chemical and genetic level along with its major side effects, scientific research has proven that lithium not only stabilizes a patient’s manic state it also brings about other benefits such as the prevention of depression, reducing the risk of dementia, and enhancing the efficiency of other psychotropic drugs (Post). Even though lithium has potentially toxic side effects (which can be easily negated through proper dosage), it is a robust drug that does more for bipolar disorder than other drugs that are combined together. Lithium is, at the present time, the foundation for successfully treating bipolar disorder and giving patients a chance at a normal life.
Work Cited
- Brady, Roscoe O, and Matcheri Keshavan. “Emergent Treatments Based on the Pathophysiology of Bipolar Disorder: A Selective Review.” Asian Journal of Psychiatry, U.S. National Library of Medicine, Dec. 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745256/.
- Cruceanu, Cristiana, et al. “Lithium: a Key to the Genetics of Bipolar Disorder.” Genome Medicine, BioMed Central, 19 Aug. 2009, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768965/.
- Lerer, Bernard. Pharmacogenetics of Psychotropic Drugs. Cambridge University Press, 2002. EBSCOhost, search.ebscohost.com/login.aspx?direct=true&db=nlebk&AN=112592&site=ehost-live.
- “Bipolar Disorder.” National Institute of Mental Health, U.S. Department of Health and Human Services, https://www.nimh.nih.gov/health/topics/bipolar-disorder/index.shtml.
- Öhlund, Louise, et al. “Reasons for Lithium Discontinuation in Men and Women with Bipolar Disorder: a Retrospective Cohort Study.” BMC Psychiatry, BioMed Central, 7 Feb. 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5804058/.
- Post, Robert M. “The New News about Lithium: An Underutilized Treatment in the United States.” Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, Nature Publishing Group, 8 Nov. 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854802/.
- Shorter, Edward. “The History of Lithium Therapy.” Bipolar Disorders, U.S. National Library of Medicine, 11 June 2009, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712976/#R9.
- Young, Wise. “Review of Lithium Effects on Brain and Blood - Wise Young, 2009.” SAGE Journals, 1 Sept. 2009, https://journals.sagepub.com/doi/full/10.3727/096368909X471251.
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