Lithium has been known as a very effective psychotropic drug since the mid-20th century. It is used primarily as a so-called phase prophylactic for bipolar and schizoaffective disorders and unipolar depression. Because the therapeutic window is very small, close monitoring of blood counts is required during lithium therapy to avoid intoxication.
What is lithium?
Lithium is used primarily as a so-called phase prophylactic for bipolar and schizoaffective disorders and unipolar depression. Lithium is a chemical element that belongs to the alkali metals. In the periodic table it is marked with the symbol “Li”. In addition to its use in industry, certain lithium salts have been used as phase prophylactics in psychiatric practice since the middle of the last century. Phase prophylactics are psychotropic drugs designed to prevent rapid, pathological mood changes. Since its discovery, lithium has been a classic in the treatment of disturbed emotional states, such as those expressed in bipolar psychosis (alternation between mania and depression). It is important to mention that lithium therapy is a preventive treatment. However, even if hereditary burdens for unipolar depression (depression without mania), bipolar psychosis, or schizoaffactive psychosis (psychosis with affective and schizophrenic elements) are known in advance, lithium cannot be administered preventively to prevent initial onset of the disorder.
Pharmacologic effects
Although lithium has long been used as a phase prophylactic and vast amounts of literature have been published on it, it is still not clear how it acts in the body. Experts believe that it acts on signal transmission between synapses (the nerve endings in the brain responsible for transmitting stimuli). One theory is that it throttles the flow of the neurotransmitter dopamine in the synaptic cleft. This is said to result in reduced excitability of the synapses. Another theory is that lithium salts affect norepinephrine and serotonin levels. Norepinephrine and serotonin are crucial messengers of emotional state. While norepinephrine levels are high during mania, depression can be attributed to insufficient serotonin levels. Some researchers suspect that the sodium–potassium current is dampened by lithium, thus lowering the general excitability of the brain. Finally, there is evidence to suggest that calcium concentrations in the body are lowered by lithium therapy. However, especially in bipolar disorders, a high calcium concentration can be observed. In addition, there is also evidence to support the hypothesis that lithium salts affect GABA receptors in the brain, resulting in decreased excitability. GABA receptors are a natural device of the brain to maintain a balance between tension and relaxation.
Medical application and use
Lithium plays a significant role in psychiatric practice because it is a very effective mood stabilizer. Its discovery as a phase prophylactic is considered a milestone in the history of pharmacology: in the 1950s, using animal experiments that originally had a very different goal, it was discovered by chance that the administration of certain lithium salts had effects on the activity of rats. Since then, lithium has been established as a phase prophylactic in recurrent depression, in mania, in bipolar psychosis, and in schizoaffective psychosis. In unipolar depression, the chemical element is most often administered in conjunction with antidepressants. Manias can be curbed by lithium in the acute stage, with a start-up time of about one week until the onset of action. In bipolar psychoses, episodes of illness can often be suppressed or at least attenuated. Schizoaffective psychoses are treated pharmacologically with a combination of neuroleptics, antidepressants and lithium. In some cases, lithium is also used in therapy-resistant schizophrenia, where it is used in combination with neuroleptics.According to numerous studies, lithium significantly reduces the risk of suicide in mentally ill patients, with about one-third of patients responding very well to the corresponding preparations, while most others experience at least a significant improvement. A prerequisite for the efficacy of lithium is that the preparation be taken regularly, since it is a mirror drug. Finally, lithium is considered a second-line treatment for cluster headache (pain between the eyes, forehead, and temples).
Risks and side effects
Although the efficacy of lithium salts has been proven in psychiatric practice with the mechanism of action still unclear, numerous unpleasant and even dangerous side effects may occur during therapy. Moreover, it should be noted that the therapeutic and toxic ranges are close to each other. At a concentration of more than one mmol/l, there is a risk of poisoning, which can lead to coma. Ideally, the level in the blood should be between 0.6 and 0.8 mmol/l and should therefore be checked every three months. Since lithium is excreted by the kidneys, regular monitoring of kidney function is also required. Patients with chronic or acute renal insufficiency must not be treated with lithium. Therapy is also prohibited in patients with heart failure. Common side effects include increased urination, increased appetite, diarrhea, vomiting, nausea, and weight gain, with excess pounds in particular affecting compliance in many patients, as they are perceived as very burdensome. If the dose is too high, sluggishness, apathy, and indifference may also occur. In addition, adequate salt intake must be ensured during lithium therapy, since lithium salts flush other salts out of the organism. In the long run, sodium levels can drop dangerously low in this way. All this makes close monitoring of medication administration necessary. Self-medication can become life-threatening with lithium.
