Forty Years of Lithium Treatment

Abstract

This review is based on a lecture in which I was requested to present my personal experiences and views. Since its introduction into psychiatry more than 40 years ago, lithium treatment has in most countries gained wide acceptance in the prophylaxis of unipolar and bipolar affective disorders. At one time it was feared that lithium treatment might lead to a decrease in the glomerular filtration rate, but systematically collected data indicate that even long-term treatment does not induce renal insufficiency. During treatment, regular laboratory monitoring of serum lithium and creatinine concentrations is recommended. Recent studies suggest that long-term lithium treatment does not raise the mortality of manic-depressive patients and indeed may have a mortality-lowering and antisuicidal effect. Despite the availability of alternative therapies, lithium remains the treatment of choice for the prophylaxis of recurrent manic-depressive illness.

5-HT1B Receptors: A Novel Target for Lithium Possible Involvement in Mood Disorders

“…Thus, these experiments strongly suggest that the interaction of lithium with 5-HT 1B receptors, observed in animal material as well as in cells transfected with animal or human genes, is likely to be extended to human tissue. Moreover, this effect occurs at concentrations of lithium (0.1-1 mM), which correlates well with the relevant therapeutic concentrations attained in the brain of patients (Schildkraut 1973;Schou and Thomsen 1975;Price et al 1990;Odagaki et al 1992;Schou 1997;Gershon and Soares 1997;Soares and Gershon 1998).…”

“…In this regard, this result opens new insights in the field of psychiatric research. First, it should substantially enhance our understanding of the biology of mania, manic depressive illness, aggression, and suicidal behavior, which are all markedly affected by lithium; and, second, it should facilitate development of alternative treatment or elaboration of novel promising therapeutic agents, because lithium is a very valuable drug, but one with substantial side-effects and a very low therapeutic safety index (Schildkraut 1973;Schou and Thomsen 1975;Wood and Goodwin 1987;Price et al 1990;Odagaki et al 1992;Price and Heninger 1994;Schou 1997;Gershon and Soares 1997;Soares and Gershon 1998).…”

“…It is widely used and remains the most effective treatment for mania and for the prevention of recurrent episodes in both mania and depression (Schildkraut 1973;Schou and Thomsen 1975;Wood and Goodwin 1987;Price et al 1990;Odagaki et al 1992;Price and Heninger 1994;Schou 1997;Gershon and Soares 1997;Soares and Gershon 1998).…”

“…5-HT 1A autoreceptors are localized on the soma and dendrites of the 5-HT neurons and control their firing; whereas, 5-HT 1B autoreceptors are localized on neuron terminals, where they are especially dedicated to the auto control of the release of 5-HT (Hoyer et al 1994). With regard to the serotonin transporter or the 5-HT 1A receptor, results are rather controversial, because some studies have shown an interaction of lithium at these levels and others did not; whereas, few biochemical data were reported for 5-HT 1B receptor (Schildkraut 1973;Schou and Thomsen 1975;Treiser and Kellar 1980;Treiser et al 1981;Wood and Goodwin 1987;Blier et al 1987;Price et al 1990;Odagaki et al 1991;Odagaki et al 1992;Plenge et al 1992;Price and Heninger 1994;Okamoto et al 1996;Schou 1997;Carli et al 1997;Gershon and Soares 1997;Soares and Gershon 1998;Redrobe and Bourin 1999). The aim of this study was to determine whether or not lithium could interact with the 5-HT system via this particular molecular target (5-HT 1B ), as was previously proposed (Blier and de Montigny 1985;Hotta et al 1986;Friedman and Wang 1988;Wang and Friedman 1988;Hotta and Yamawaki 1988;Hide and Yamawaki 1989;Redrobe and Bourin 1999).…”

White matter hyperintensity detected by magnetic resonance imaging and lithium response in bipolar disorder: A preliminary observation

“…Although there are now several available mood stabilizers, 1 lithium is still the drug of first choice for maintenance treatment for bipolar disorder. 2 However, lithium is not effective for all bipolar patients. Lithium can completely prevent recurrence in only 50% of patients with bipolar disorder, while other patients are completely resistant to lithium treatment or show only a partial response.…”