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Lithium Therapy in Treating Bipolar Depression

Lithium had been discovered nearly 200 years ago during a mineralogical expedition to Sweden.

While the expedition a Brazilian scientist Jose de Andrada discovered two new minerals in an iron ore mine. One mineral he named petalite and the other one – spodumene. Then, in 1817, a Swedish chemist Johan August Arfwedson determined the composition of the mineral petalite and discovered that 4% contained a previously unknown alkali metal that was named as a lithion – the name suggested by Baron Jons Jacob Berzelius (Arfwedson’s supervisor).

After 1841, when Dr. A. Lipowitz discovered that lithium corbonate salts dissolve uric acid, lithium became a common cure-all (it was added even in water and beer). Then in 1886, a Danish internist Carl Lange reported that lithium salts play a therapeutic and preventing role in treating recurrent depression. Lithium was first treated as antidepressant, about what was written in the book The Most Important Groups of Insanity (1894) by Lange’s brother Fritze Lange. That work was eventually lost, and many years pass before lithium effect was again rediscovered.

John F.J. Cade, an Australian, initiated several studies with lithium salts (1949), as he believed that lithium injections might possess antiexcitement properties. Lithium was first prescribed as medicine to treat bipolar disorder. He described the psychoactive properties of lithium and reported that doses of lithium citrate countered pathological excitability in acutely manic patients. Also other Australians Noack and Trautner observed the effect of lithium therapy in manic patients (1951).

But the one, who actually gave lithium to the world, was a young Danish psychiatrist, Mogens Schou. In 1954 he arranged the first double-blind (the patients and doctors did not know when the drug was given), placebo-controlled study of lithium in acute mania. But when the results were published, no statistical analysis to the data was applied. Only in 1963 the first double-blind study that was done according to modern standards, was properly published. That study was conducted by Ronald Maggs in England; and then in 1968 (American study) - by Bunney, Goodwin, Fawcett and Davis.

A research team headed by Ronald R. Fieve in their study (1970) found out the drug’s effectiveness in manic patients who were resistant or allergic to phenothiazine (that actually served as a basis of drug efficacy whether lithium shortened the length of attacks in comparison to early episodes of attacks). Another study conducted by Dr. William E. Bunney gave more information that helped to understand the nature of lithium effectiveness (the study employed comprehensive methods). Two results of the study were the following: both patients who received lithium were restored to normal mood states and their behaviors were dramatically sensitive to the temporary withdrawal of lithium. So, reinstitution of lithium requires a longer time to restore the patient back to a normal state.

All the studies demonstrated that lithium is effective, but in previous studies the effectiveness was somehow overestimated; also that some other agents (such as benzodiazepines and neuroleptics) are as effective as lithium, but much safer.

What is it used for?

So, lithium is the most important issue in prophylactic treatment of patients having bipolar (manic-depressive) disorders, as well as in unipolar depression.

Bipolar disorder (the medical term for manic-depression)  is a mental illness and is described as a neurobiological brain disorder involving extreme mood swings.

Although the drug is effective in treatment of both types of disorders, lithium is more often used in that of recurrent bipolar depression.

The amount of lithium needed to treat or prevent depressive and manic symptoms effectively differs greatly from one patient to another. Moreover, the older patients obtain greater benefit from treatment than the younger. The most crucial point about taking lithium for health purposes is that the amount of the drug needed to be effective is only slightly less than the amount that is toxic. And according to the researches of lithium intoxication cases, almost all of the cases during nine-year period developed because of the deliberate self-poisoning.

How do you take lithium?

Lithium is usually given orally as a salt in the form of a capsule or tablet, but it can be injected intravaneously as well. When the lithium enters the stomach and gut, lithium ions separate from their anionic partners and rapidly enter the bloodstream, where they pass into various tissues. Lithium is freely transported with blood cells by the blood plasma quickly into kidney, more slowly into liver, bone, and muscle, and most slowly into brain. The lithium ion travels through the glomerular membrane, where it is filtered and excreted in urine. For the removal of half the lithium, it takes approximately 24 hours for average adults, almost 36 hours for elderly people, and little less than 18 hours for youngsters.

So, the doctor needs to determine the patient’s lithium clearance for the proper dosage of the drug and to avoid lithium accumulation and toxicity in the blood. The doctor determines it by taking a sample of blood from time to time. Systematical blood test is also required, as lithium levels in the blood can change even when the patient takes the same dose every day (as, for example, the concentration of the drug can increase when a person becomes ill with another medical condition, especially influenza or other illnesses that result in fever or changes in diet and loss of body fluids; or crash diets and surgery). (By the way, it is important to have blood drawn about 12 hours after the last dose of lithium, not earlier.) For these reasons the doctor should always know patient’s illness or changes in eating habits. It is important not to forget to take the dose, as if you stop taking lithium for only one day, the blood level of the drug falls to half that needed for effective therapy.

The mechanism of action of lithium is still a mystery, although lots of hypotheses are being proposed today and experiments are being conducted to reach a conclusion concerning the topic. Some processes of how lithium affects body are also not very well understood.

Lithium’s side effects

In the beginning of the lithium therapy most patients do not experience serious side effects. And unlike other antidepressant drugs, lithium rarely produces undesirable effects on emotional and intellectual functioning. Still, treating with the help of lithium therapy has some adverse effects that can be divided into three groups:

  1. Side effects that arise during the initiation of treatment – most common are gastrointestinal discomforts (diarrhea, nausea, stomach pain,vomiting, nausea-muscular weakness, thirstiness and frequent urination, feelings of being dazed, sleepy, and tired, and hand tremor). After several days of treatment these effects normally do not bother patient any more.
  2. Side effects that are produced in the late stages of the therapy – the most common are hand tremor (Although this is a syndrome of Parkinson’s disease, it does not respond to anti-Parkinson drugs),constant thirst and excretion of abundant amounts of urine (that mounts to six or seven times the normal amount) and thyroid enlargement (caused by lithium’s perturbation of the thyroid functioning).
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  4. Side effects caused by toxicity of lithium in the tissues - sluggishness, drowsiness, languidness, coarse tremor of muscular twitching, vomiting, diarrhea, dysarthria, and loss of appetite. Other effects of lithium poisoning involve the nervous system.

When taken with a permanent doctor’s supervision in proper dose, lithium can be fully effective and control manic-depressive illness for the rest of a person's life. But it is not a cure. Like antihypertensive medications for controlling high blood pressure, lithium should not be discontinued without consulting the physician.

Valentyna Ant.

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