Mania

The manic phase is characterized by exaggerated elation, flight of ideas, and a pathologically increased psychomotor drive. This is symbolically illustrated in A by a disjointed structure and aggressive color tones. The patients are overconfident, continuously active, show progressive incoherence of thought and loosening of associations, and act irresponsibly (financially, sexually etc.).

Lithium ions. Lithium salts (e.g., acetate, carbonate) are effective in controlling the manic phase. The effect becomes evident approx. 10 d after the start of therapy. The small therapeutic index necessitates frequent monitoring of Li+ serum levels. Therapeutic levels should be kept between 0.8-1.0 mM in fasting morning blood samples. At higher values there is a risk of adverse effects. CNS symptoms include fine tremor, ataxia or seizures. Inhibition of the renal actions of vasopressin (p. 164) leads to polyuria and thirst. Thyroid function is impaired (p. 244), with compensatory development of (euthyroid) goiter.

The mechanism of action of Li ions remains to be fully elucidated. Chemically, lithium is the lightest of the alkali metals, which include such biologically important elements as sodium and potassium. Apart from interference with transmembrane cation fluxes (via ion channels and pumps), a lithium effect of major significance appears to be membrane depletion of phosphatidylinositol bisphosphates, the principal lipid substrate used by various receptors in transmembrane signalling (p. 66). Blockade of this important signal transduction pathway leads to impaired ability of neurons to respond to activation of membrane receptors for transmitters or other chemical signals. Another site of action of lithium may be GTP-binding proteins responsible for signal trans-duction initiated by formation of the agonist-receptor complex.

Rapid control of an acute attack of mania may require the use of a neuroleptic (see below).

Alternate treatments. Mood-stabilization and control of manic or hy-pomanic episodes in some subtypes of bipolar illness may also be achieved with the anticonvulsants valproate and carbamazepine, as well as with calcium channel blockers (e.g., verapamil, nifed-ipine, nimodipine). Effects are delayed and apparently unrelated to the mechanisms responsible for anticonvulsant and cardiovascular actions, respectively.

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