Lithium became the first effective medication in the field of psychiatry and remains, until today, the “golden standard” for treatment of bipolar disorder. Psychiatrists use lithium in the long-term treatment of bipolar disorder, stabilizing mood and preventing the extreme highs and lows. Lithium protects the patients from both manic and depressive episodes. In most of the patients, lithium does not cause any side effects.
Lithium is not metabolized in the body and is eliminated only through the kidneys. The lithium plasma level varies individually. Therefore, the psychiatrist must adjust the lithium dosage in each patient to achieve the full therapeutic effect.
Read more about anxiety disorders:
- Bipolar Disorder, Diagnostic & Treatment
- What is Mania and Hypomania?
- Cyclothymic Disorder
- History of Treatment of Bipolar Disorder
- CANMAT Guidelines of Bipolar Disorder Treatment with Medication
- Mood Stabilizers in Treatment of Bipolar Disorder
Lithium, History
The therapeutic effect of lithium as a mood stabilizer in the treatment of bipolar disorder was discovered in 1948 by an Australian psychiatrist, John Cade. Cade published his findings in the Medical Journal of Australia in a paper titled “Lithium salts in the treatment of psychotic excitement.” Cade was a pioneer and father of psychiatric research. His discovery, similar to Fleming’s discovery of penicillin, in later years changed the fate of millions of people. The portrait of Cade and the story of his research are presented in the movie “Troubled minds, the lithium revolution”.
Cade himself did not recognize the importance of his discovery. It was the Danish psychiatrist Mogens Schou who first introduced lithium into psychiatric treatment. He fought for years to have lithium accepted for treatment of bipolar disorder. Schou knew the condition very well, as his brother suffered from bipolar disorder. Beginning in the 1950s, Schou and his fellow psychiatrist Poul Baastrup conducted experiments on lithium. In 1970 they published, in The Lancet, the result of a double-blind, placebo-controlled clinical trial (evidence-based scientific method) proving beyond doubt the healing effect of lithium and establishing lithium as an effective medication for most people with bipolar disorder, including Schou’s brother (P. C. Baastrup et al. Lancet 296, 326–330; 1970).
Diagnostics Before Lithium Therapy
When starting lithium treatment as a long-term mood stabilizer, initially more frequent monitoring of lithium plasma level is necessary. To keep the plasma level stable, lithium level controls should be performed every three months in younger individuals and every two months in older persons. Additionally, the lithium level should be measured with every dose change or when other medications are added.
Lithium Mechanism of Action
Lithium has significant effects on the functionality of nerve cells and influences a wide range of neurochemical systems, including:
- Ion channels
- Neurotransmitters, such as serotonin, dopamine, and norepinephrine
- Second messenger systems, including phosphoinositol- and cAMP-based pathways
Additionally, lithium appears to protect and even increase the volume of brain structures involved in emotional regulation, such as the prefrontal cortex, hippocampus, and amygdala. This may reflect its neuroprotective properties. At the neuronal level, lithium reduces excitatory activity (dopamine and glutamate) while enhancing inhibitory (GABA) neurotransmission.
At the intracellular and molecular levels, lithium targets second messenger systems that further modulate neurotransmission. For example, its effects on adenylate cyclase, phosphoinositol, and protein kinase C may help dampen excessive excitatory neurotransmission.
Beyond these mechanisms, lithium’s neuroprotective effects have been suggested as a key factor in its therapeutic benefits. Research has shown that lithium reduces oxidative stress, which is elevated in mania and depression. It also increases protective proteins such as neurotrophins and Bcl-2, while reducing apoptotic processes by inhibiting glycogen synthase kinase 3 (GSK-3) and autophagy.
Avoiding Side Effects of Lithium
Despite so many years since its beneficial effect in bipolar disorder has been discovered, lithium remains the “golden standard.”. In most of the patients, lithium does not cause any side effects and is not limiting the life quality of the patients. Apart from that, lithium protects patients not only from manic mood swings but also from depressive episodes.
Lithium is eliminated only through the kidneys and not metabolized in the body. The psychiatrist must adjust the lithium dosage individually in each patient not only to achieve the full therapeutic effect but also to avoid side effects. To allow the patient to “sleep through” any potential side effects, a single evening dose of lithium can be used.
One of the side effects of lithium therapy is tremor. Hand tremor is usually observed at the beginning of treatment and is often caused by a rapid dose increase or a high serum lithium level. In the majority of the cases, tremor can be avoided by a gradual increase in the dosage or by keeping the plasma level low but still therapeutically effective. It would be incorrect to discontinue lithium immediately upon the first occurrence of a tremor.
A small percentage of patients treated with lithium might experience interactions with the thyroid gland. People with a predisposition to hypothyroidism or a family history need closer monitoring during the first year of treatment.
Treatment with Lithium for Bipolar Disorder in Dubai. Summary
Lithium is still considered the gold standard for preventing relapses in bipolar disorder. Lithium prophylactic and anti-manic properties are well established, with its preventive effects being stronger against manic episodes than depressive ones. Lithium should not be used as a monotherapy for acute unipolar or bipolar depression. However, it has strong evidence as an augmentation strategy when combined with an antidepressant.
Lithium can be used to treat acute mania, alone or in combination with antipsychotics. If transitioning to long-term maintenance therapy, lithium is considered a first-line medication.