Pathological Neurotoxicity with Lithium

Though lithium-induced neurotoxicity usually occurs when serum lithium exceeds 2.0 mEq/1, reports document its occurrence with serum lithium within the therapeutic range (Strayhorn and Nash 1977, Hansen and Amidsen, 1978, Speirs and Hirsch 1978, West and Meltzer 1979). Neurotoxicity has even been described with serum lithium between 0.4 and 0.5 mEq/1 (Hansen and Amidsen 1978). Such may best be conceptualized as pathological neurotoxicity, in the sense that the expected side effect is obtained at a far lower dose or level than is usual. Many hypotheses have been suggested to explain this pathological neurotoxicity. These include: interactions with other drugs such as haloperidol and diuretics (Strayhorn and Nash 1977), diphenylhydantoin (Speirs and Hirsch 1978) and phenothiazines (Spring 1979), tissue retention and seizure diathesis (Strayhorn and Nash 1977), high pretoxic global ratings of psychotic symptomatology and anxiety (West and Meltzer 1979), old age (Van der Velde 1971), Schizophrenia (Shopsin and Gershon 1973) and intercurrent medical illness (Shopsin and Gershon 1973, Strayhorn and Nash 1977).