Mood stabilizers

Indications for use

Mood-stabilizing agents are used to treat conditions associated with severe affective disorders. The main clinical indications are:

• Bipolar affective disorder (BAD, also known as manic-depressive psychosis). This disease manifests as regular alternation of depression and mania episodes, between which the patient experiences lucid intervals of full recovery — remissions.
• Cyclothymia. This mental disorder is characterized by chronic mood instability. Unlike true manic-depressive psychosis, the frequent alternation of periods of emotional downturn and uplift is less abrupt and does not reach great depth.

Drugs of this group effectively relieve manic syndrome. Mania is characterized by pathological elation, morbidly increased agitation, excessive physical activity, as well as a marked acceleration of speech and movement.

Drug classification

For reliable stabilization of the emotional background, two main groups of medications are used in clinical practice:

1. Lithium salts — the baseline group of mood stabilizers.
2. Antiepileptic drugs — in this context, these include carbamazepine and valproic acid.

Antiepileptic drugs are prescribed for the prevention of manic-depressive states. Often, they are used as part of combination therapy: they supplement lithium salts if monotherapy with the latter proves insufficiently effective.

Pharmacodynamics of lithium salts

The exact mechanism of action of lithium has not yet been definitively established, but pharmacology distinguishes three key hypotheses:

• Ionic mechanism. Lithium ions are capable of penetrating inside neurons through fast sodium channels. Accumulating inside the cell, they physically block the transmembrane transport of sodium ions, which ultimately leads to a disruption of normal depolarization processes of cell membranes.
• Effect on neurotransmitters. The drugs actively interfere with monoamine metabolism in central nervous system structures.
• Intracellular mechanism. Lithium disrupts the production of crucial second messengers that transmit signals inside the cell (these include cAMP, diacylglycerol, and inositol 1,4,5-trisphosphate).

Features of lithium therapy

The primary representative of the group is lithium carbonate. It is well absorbed from the gastrointestinal tract, but its therapeutic effect develops rather slowly — a latent period of about 2–3 weeks is required. The drug has a selective antimanic effect, while not causing a pronounced sedative effect. Therapy is prescribed for a long period (years) for reliable prevention of manic and depressive phases in BAD.

In addition to standard forms, there are prolonged-release drugs (for example, Contemon, domestic Mikalit) and alternative salts (lithium oxybutyrate). Prolonged-release variants, due to the slow release of the active substance, irritate the intestine less and are characterized by low hygroscopicity.

Safety profile and toxicity

Lithium salts have a narrow therapeutic index, which makes them potentially dangerous to use and requires strict monitoring.

• Side effects: patients often complain of severe thirst, nausea, tremor, polyuria, and muscle weakness.
• Toxic effect: occurs if the therapeutic concentration in the blood is exceeded by just 2–3 times. Acute poisoning manifests as intractable vomiting, convulsions, ataxia, and can quickly lead to coma.

Since lithium preparations are excreted from the body predominantly by the kidneys, any renal pathology is an absolute contraindication to their administration. Impairment of excretory function inevitably leads to substance cumulation and a sharp spike in toxicity.

Class and exam questions

What else to study on this topic

• Ionic mechanism of lithium action: blockade of fast sodium channels and impaired depolarization.
• The effect of mood stabilizers on monoamine metabolism in the central nervous system.
• The role of second messengers (cAMP, diacylglycerol, inositol 1,4,5-trisphosphate) in the intracellular effects of lithium.
• Comparative characteristics of standard and prolonged-release forms of lithium (Contemon, Mikalit).
• Features of the use of valproic acid and carbamazepine as mood stabilizers.

Other topics in the section "Agents Used in Psychiatry and Neurology"

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