Withdrawal from lithium

Numerous studies have now confirmed that withdrawal from lithium causes adverse psychiatric reactions. Cavanagh et al. (2004), in a 7-year follow-up, found that lithium withdrawal caused both mania and depression. They concluded, These results confirm that acute discontinuation of lithium leads to a high immediate relapse rate. However, they did not find that this justified the continuation of lithium. To the contrary, outcome was not worsened by discontinuation. ... 

If rapid withdrawal from high lithium levels can produce mania and disable neurologic reactions, then it is probable that rapid withdrawal from lower levels may produce more subtle adverse reactions. 

Withdrawal From Lithium and Other Mood Stabilizers... 

Withdrawing from lithium must be treated as a potentially high-risk event requiring clinical monitoring and as much family support as possible. Although the data are sparse, any drug used as a mood stabilizer should be considered a risk for causing withdrawal mania. 

The observation that rapid or abrupt lithium withdrawal might be associated with a more immediate or higher likelihood of recurrence has gathered further support from a reanalysis of data from a double-blind lithium maintenance study, in which the benefits of low serum concentrations (0.4-0.6 mmol/1) and standard serum concentrations (0.8-1.0 mmol/1) were compared (458). Recurrence rates were greater only in those whose concentrations were abruptly reduced from standard to low at the start of the study. The authors suggested that rapid dosage reduction, rather than a low maintenance concentration itself, accounted for their initial conclusion that standard concentrations were more effective than low concentrations. 

Heavy caffeine consumption may increase the renal clearance of lithium. Therefore, withdrawal from caffeine can result in increased serum lithium concentration. ... 

Alkyllithium bases are generally less suitable for deprotofiation of compounds with strongly electron-withdrawing groups such as C=0, COOR and CsN. In these cases lithium dialkylamides, especially those with bulky groups (isopropyl, cyclohexyl), are the reagents of choice. They are very easily obtained from butyllithium and the dialkylamine in the desired solvent. 

Keywords imines derived from formylphosphonate undergo Diels-Alder reactions only in those cases which carry a strongly electron-withdrawing N-substituent. Lewis acidity, solvent effect, lithium perchlorate in diethyl ether... 

The attempt to use these salts originated from the hope that their dissociation constants would be high even in low dielectric media, and the organic nature of perfluorinated alkyls would always assist the solubility of the salts in nonaqueous solvents. Because of the requirement for electrochemical stability, lithium carboxylates (RF-C02Li, where Rp- = perfluorinated alkyls) are excluded from consideration, because their oxidation still occurs at - 3.5 V vs lithium, which is similar to the cases of their non-fluorinated counterparts. Obviously, the electron-withdrawing groups do not stabilize the carboxylate anions sufficiently to alter their oxidative stability. 

Among the three subcategories, boronate compounds seemed to be the most efficient in coordinating with anions and enhancing lithium ion stability, although the number of electron-withdrawing substituents in boronate is only two. The authors thus inferred that the ability of these anion receptors to capture an anion depends not only on the electron-deficiency of the core atom but perhaps also on the steric hindrance presented by these substituents on the core. With only two substituents, the core of the boronates is obviously more exposed and therefore more easily accessible for an anion. The higher ion conductivity achieved by boronate additive therefore comes from the better balance between the electron-deficiency and steric openness of this compound as... 

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