Lithium Treatment for Bipolar Disorder: Discovery, Uses, Effects and More

The lightest metal can have the strongest impact on our brain and even rid people of the most severe forms of depression

According to experts, in the United States and Europe, almost half a million people take lithium drugs in order to reduce mood swings in manic-depressive syndrome. This metal may play an important role in the control of brain neurotransmitters and, as a result, has a calming effect in severe mental disorders that are not treated with conventional antidepressants.

Lithium therapy is not a correction of a lack of an important element in the body. Apparently, the human body does not have a biological need for this metal, but it is present in our body in a small amount. Lithium is widely distributed in nature, and we consume it daily with food and water. Its concentration in food is minimal. We get lithium from food when digested, but absorbed lithium is easily excreted from the body, so this element does not accumulate in our tissues and organs. The body of an average adult person contains about 7 mg of lithium, its concentration in the blood is approximately four parts per billion parts, which indicates the low significance of the element for human biochemistry. The low content of lithium in our body is not surprising, considering the fact of how little it is contained in the food we eat.

We can not unequivocally assert that lithium has no biological role in the animal world since at least some experiments prove that this element can be significant for living beings. For example, goats that are on a non-lithium diet from the moment they are born to have less weight compared to those who receive normal nutrition.

Unconsciously, people have long used lithium for the treatment of diseases. The waters of ancient Ephesus, formerly the Greek city, now owned by Turkey, were famous for their beneficial effects on the brain. This, in particular, was written by Soranus of Ephesus, who was born in the second century BC and practiced medicine in Rome. He specialized in gynecological diseases, but in his book “Acute and chronic diseases” was a chapter devoted to the treatment of nervous diseases. Indeed, water in the area of Ephesus contains lithium at a higher concentration than in other areas, although this concentration is still not high enough to have a significant therapeutic effect.

The history of lithium discovery

The history of lithium begins at the end of the 18th century. The first lithium-containing mineral was petalite, discovered by the Brazilian scientist Jose Bonifacio de Andrada Silva on the Swedish island of Uto in 1790. When the researcher began to study its composition, the mass of known elements turned out to be less than the mass of the mineral, which puzzled the scientist. The puzzle was solved in Stockholm in 1817 when Augustus Arfvedson (1792-1841) conducted a more thorough analysis of the mineral. This took a long time, and eventually, the researcher managed to find out the composition of the substance only by 96%, but from his research, Arfvedson was able to make the correct deductive conclusion.

In January 1818, the scientist attributed a mysterious 4% to the new, previously unknown metal and announced the discovery of lithium, which was attributed to the group of alkali metals. Arfvedson called the element “lithium“, because it was found in stone, and in ancient Greek lithos means “stone.”

In the same year, it was discovered that falling into the flames, lithium colored it in a beautiful red color, express test for the presence of metal is based on this property. Soon after that, lithium was discovered in other minerals, as well as in the mineral waters of Carlsbad, Marienbad and Vichy. To register trace amounts of lithium, a more sensitive method was required than a simple flame analysis, and soon such a method appeared, it was spectroscopy, which made it possible to detect lithium on the characteristic red band of the spectrum. With this method, in 1859 metal was detected in seawater (at a concentration of 0.17 ppm), followed by the presence of an element in grapes, seaweed, tobacco, various vegetables, milk, blood and human urine.

Although lithium, together with sodium and potassium, refers to alkali metals, Arfvedson did not succeed in isolating it by electrolysis, as did Humphry Davy with other alkali metals. In 1821, William Brande received pure lithium, but in such a small amount that it was not enough to even find out the properties of the element. It was necessary to wait until 1855 when the famous German chemist Robert Bansen (1811-1899) and the less famous British chemist August Mattison (1831-1870) received lithium in quantities sufficient to study the properties of the metal. For this, they used electrolysis of molten lithium chloride.

The use of lithium in medicine

Lithium carbonate is one of the most important lithium-containing substances, being poorly soluble in water, it easily crystallizes out of solutions. It is used for cleaning aluminum, in the production of glass, enamel, and ceramics, as well as for the production of other substances containing lithium. In the form of purified carbonate, lithium is prescribed for the treatment of the most severe forms of depression. Today, you can buy cheap Lithium in regular pharmacies or in online pharmacies, including but not limited to Canadian Pharmacy.

In the 19th century, lithium was a popular treatment for gout – a painful condition in which acute uric acid crystals are deposited in the joints, especially in the joints of the legs. Uric acid is poorly soluble in water, therefore, once formed crystals may not disappear for a long time. Due to the fact that lithium salts of uric acid are highly soluble in water, Dr. Ure in 1843 suggested that drinking water rich in lithium would promote the excretion of uric acid crystals. This theory was popularized by the famous physician Sir Alfred Garrod, who observed how quickly lithium carbonate dissolves uric acid crystals in a test tube and recommended taking it in large doses to people suffering from gout. The theory of the therapeutic properties of lithium lasted more than half a century until in 1912, Dr. Pfeiffer showed that taking lithium-containing substances slows the excretion of uric acid in patients with gout.

In the meantime, some doctors have tried to use lithium to treat a number of other conditions. In 1864, information on lithium salts appeared on the pages of the British Pharmacopoeia, in which lithium carbonate was considered an agent for the treatment of indigestion, and lithium citrate was attributed to diuretics. In 1871, William Hammond recommended large doses of lithium bromide for the treatment of “acute mania” and “acute melancholia,” and the Danish neurologist Karl Lange prescribes a mixture of alkali metal salts, in which lithium was the main component, for the treatment of “periodic depression”. These methods of therapy were ahead of their time and were not accepted by the medical world. In 1949, Australian Dr. John Cade made a scientific breakthrough and proved that lithium is the best way to treat such mental conditions.

After the Second World War, lithium chloride was sold under the commercial name “Westall”, it was intended for people with heart disease who were on a salt-free diet. In 1949, several patients died of lithium poisoning, this was announced in the press and on the radio. The US Food and Drug Administration has banned the use of all lithium salts and conducted its own studies showing that high doses of lithium can have a detrimental effect on kidney function. The ban on lithium lasted about 20 years, after which it was withdrawn in connection with favorable reviews of lithium therapy, both from patients and from doctors.

Usually, lithium is prescribed in the form of lithium carbonate tablets, treatment is most effective when the level of lithium in the blood reaches a level between 0.6 and 1.2 millimol per liter. A dangerous dose of lithium carbonate starts with 2.5 grams, and its concentration in the blood of 15 mg per liter indicates a slight lithium poisoning. With the long-term use of lithium, various renal impairments can develop, therefore the maximum duration of lithium intake is five years, and during the treatment, patients should regularly undergo monitoring of renal function.

The mechanism of lithium action

Nowadays, doctors rarely prescribe drugs with an unknown mechanism of action, and lithium also applies to this category of drugs, although there are theories about how it works. The first theory was developed in the 1980s by Michael Burridge. In his opinion, lithium reduces the level of inositol, a sugar-like molecule contained in the cellular membranes of the whole organism, including the brain. Other parts of the body can contain inositol in the form of inositol phosphate and receive it with food, especially with cereals, vegetables and citrus fruits, but none of these molecules coming from outside get into the brain, all necessary inositol is synthesized directly in the brain cells. The production and metabolism of this substance can be regulated by lithium, which can pass through the blood-brain barrier.

Inositol monophosphatase is an enzyme that regulates the sensitivity of brain cells to external stimuli, and if the sensitivity of the latter is too high, it can lead to sudden mood changes and manic behavior. Lithium inhibits the activity of inositol monophosphatase, but only in those cells where it is increased, this may explain why lithium does not affect people who are not depressed.

Another explanation for the mechanism of lithium action was suggested by a group of researchers from Merck Sharp & Dohm. Howard Bruton, Scott Pollack, and John Aitak examined the effect of lithium on enzymes and concluded that this metal binds to protein sites originally intended for magnesium binding, which is why protein molecules no longer function properly.

At first glance, such interchangeability of metals seems rather strange from the point of view of chemistry, since magnesium and lithium are in different groups of the periodic system. Lithium is located in the first group, and magnesium in the second, in connection with this their ions are differently charged: Li +, Mg + 2. But, despite this, these metals have similar chemical properties, which is due to the so-called diagonal similarity of the elements of different groups.

There is one more theory about the mechanism of action of lithium. Dr. Adrian Harewood of the University College of London believes that the ion inhibits the enzyme glycogen synthase kinase-3, which is involved in the transmission of intracellular signals.

The work on studying the mechanism of lithium action continues; as long as the mechanism remains unclear, we can not find an alternative safe preparation or make lithium therapy more targeted, which would allow us to prescribe smaller doses of metal and continue treatment as long as necessary. Although the action of lithium on our body is not fully understood, its salts remain an indispensable tool for treating severe forms of depression.

In 1991, a book entitled “Lithium in Biology and Medicine” was published, it contained data from epidemiological studies conducted in the United States, these data indicate that regions where drinking water contains relatively large amounts of lithium, more than 70 parts per billion parts of water have a lower crime rate and a lower incidence of suicide. Using the method of elementary deduction, one can advise the authorities of those regions where the problems of crime and suicide are particularly acute, increase the concentration of lithium in drinking water. However, it is unlikely that this metal will ever be used in this way, at least because of its high cost. And even if any water company agrees to conduct such an experiment, it would take many years to reliably confirm the positive effects of lithium.

Lithium can also be used to treat certain other diseases, for example, lithium-based creams have shown their effectiveness in the therapy of genital herpes, that is, they can help in the fight against a disease that in some cases can lead patients to depression.