Manic-depressive illness, lithium

For patients with bipolar affective disorder (manic-depressive illness) lithium, usually in the form of lithium carbonate, has been the main prophylactic agent for the last forty years. However, during the last ten years certain anticonvulsants (carbamazepine and sodium valproate) have also been found to be effective. 

Lithium is the major drug used to treat the mood disorders of mania and manic-depressive illness. Lithium is the only psychotherapeutic drug that is an effective prophylaxis against disease recurrence. 

Treatment of Manic—Depressive Illness. Siace the 1960s, lithium carbonate [10377-37-4] and other lithium salts have represented the standard treatment of mild-to-moderate manic-depressive disorders (175). It is effective ia about 60—80% of all acute manic episodes within one to three weeks of adrninistration. Lithium ions can reduce the frequency of manic or depressive episodes ia bipolar patients providing a mood-stabilising effect. Patients ate maintained on low, stabilising doses of lithium salts indefinitely as a prophylaxis. However, the therapeutic iadex is low, thus requiring monitoring of semm concentration. Adverse effects iaclude tremor, diarrhea, problems with eyes (adaptation to darkness), hypothyroidism, and cardiac problems (bradycardia—tachycardia syndrome). 

Manji HK, Chen G. Lithium upregu-lates the cytoprotective protein bcl-2 in vitro and in the CNS in vivo, a role for neurotrophic and neuroprotective effects in manic-depressive illness. J Clin Psychiatry 2000 61 82-96. 

Schwab AB, O Connell ME, Long SE (1995) The use of lifiiium concenh ation data and isotopic ratios as hydrologic tracers in a first-order catchment. Geol Soc Am Prog Abst 27 A97 Schou M (1988) Lithium h eahnent of manic-depressive illness—Past, present and perspectives. J Am Med Ass 259 1834-1836... 

Lithium ions inhibit thyroxine release. Lithium salts can be used instead of iodine for rapid thyroid suppression in iodine-induced thyrotoxicosis. Regarding administration of lithium in manic-depressive illness, see p. 234. 

Lithium was first used to treat manic-depressive illness in 1949, but was not used in the United States until 1970 due to concerns for its toxicity. When used as a therapeutic agent, lithium blood levels must be kept within a very narrow range (i.e., a narrow therapeutic index). Lithium appears to be non-essential, but it is readily absorbed by the intestine and is found in plants and meat. Normal daily intake is about 2 mg. Lithium is used in some manufacturing processes, as a lubricant, and as an alloy. 

Lenox RH, Manji HK Lithium, in The American Psychiatric Press Textbook of Psychopharmacology. Edited by Nemeroff C, Schatzberg A. Washington, DC, American Psychiatric Press, 1995, pp 303-349 Lenox RH, Watson DG Lithium and the brain a psychopharmacological strategy to a molecular basis for manic-depressive illness. Chn Chem 40(2 309-314, 1994 Lenox RH, Watson DG, Patel J, et al Chronic lithium administration alters a prominent PKC substrate in rat hippocampus. Brain Res 570 333-340, 1992 Lenzi A, Lazzerini F, Grossi E, et al Use of carbamazepine in acute psychosis a controlled study. J Int Med Res 14 78-84, 1986 Leonard BE Commentary on the mode of action of benzodiazepines. J Psychiatr Res 27 (suppl 1) 193, 1993... 

Stokes PE, Shamoian CA, Stoll PM, et al Efficacy of lithium as acute treatment of manic-depressive illness. Lancet 1 1319-1325, 1971... 

Despite this favorable result, lithium was hardly considered as a psychopharmaceutical for many years. There were a variety of reasons for this. Firstly, mania is not a very common psychosis and there is spontaneous remission in many cases. There were thus not so many occasions where lithium treatment was indicated. Secondly, lithium salts were considered to be toxic because for some time they had been given in excessive doses to patients with heart failure and in this way, had led to a number of fatalities (Cade, 1970). Thirdly, a few years after Cade s first publication psychiatrists attention had been claimed by chlorpromazine and the subsequent neuroleptics and antidepressants, thus explaining why lithium almost fell into oblivion. It was onl> in the 1960s that it once more attracted some interest, after the Danish psychiatrist Mogens Schou had shown that lithium salts were not only useful in the manic phase of manic depressive illness but also could prevent depressive episodes in patients suffering from bipolar psychoses. 

Dorus E, Pandey GN, Shaughnessy R, et al. Lithium transport across red blood cell membrane a cell membrane abnormality in manic-depressive illness. Science 1979 205 932-934. 

Moore GJ, Bebchuk JM, Parrish JK, et al. Temporal dissociation between lithium-induced changes in frontal lobe myo-inositol and clinical response in manic-depressive illness. Am J Psychiatry 1999 156 1902-1908. 

Schou M. Lithium treatment of manic-depressive illness a practical guide, 3rd ed. Basel, Switzerland Karger, 1986. 

Mander AJ. Use of lithium and early relapse in manic-depressive illness. Acta Psychiatr Scand 1988 78 198-200. 

Prien RF, Caffey EM Jr, Klett CJ. Prophylactic efficacy of lithium carbonate in manic-depressive illness. Arch Gen Psychiatry 1973 28 337-341. 

An interesting application of lithium that is relatively well supported by controlled studies is as an adjunct to tricyclic antidepressants and selective serotonin reuptake inhibitors in patients with unipolar depression who do not respond fully to monotherapy with the antidepressant. For this application, concentrations of lithium at the lower end of the recommended range for manic-depressive illness appear to be adequate. 

O-antigen of 180 structures of 430 Lipoprotein(s) 58 bacterial 428 Liposomes 392, 392-394 NMR spectra 396 Liquid crystals 392-394 Liquid crystalline phases 392 Lithium salts, in treatment of manic-depressive illness 564 Lithostatine 443 Liverworts 29... 

An effective treatment for bipolar disorder (manic -depressive illness) is the administration of lithium salts 445/1111-11133 Inhibition of the hydrolysis of inositol phosphate by Li+ (Fig. 11-9) may be related to its therapeutic effect. Reduced phosphatidylinositol turnover may dampen responses to neurotransmitters.1114 Li+ may affect gene expression in neuropeptide-secreting neurons.1115 Bipolar disorder apparently has more than one cause. There are strong indications of genetic susceptibility,1116 and genes that increase susceptibility have been located on chromosomes 4,12,13,18,21, and X.1117... 

Sapse, Anne-Marie and P.von Rague Sclileyer Lithium Chetnistrs A Theoretical and Exfienmental Overview. John Wiley Sons. Inc.. New York. NY. 1994. Schou. M, Lithium Treatment of Manic Depressive Illness A Practical Guide. S. 

The use of lithium in medicine has been the subject of recent reviews by Birch,81 Birch and Sadler29 and references therein, and Tosteson.82 Historically, the use of lithium in medicine began with the treatment of gout and rheumatics in 1859. For the following 90 years, lithium was proposed for a variety of disorders and then discarded for example, lithium bromide was considered to be an effective sedative. In 1949 lithium was introduced into psychiatric practice and lithium carbonate, LijCOj, became the first of the modern psychotropic drugs. In a review of double-blind trials Schou and Thomsen (1975) support the prophylactic use of this drug in bipolar (manic-depressive) illness. 

The uses of lithium fall into two categories established and innovative. Among its established uses, lithium salts are used to treat acute mania and as a prophylactic measure to prevent the recurrence of bipolar manic-depressive illness. As an innovative agent, lithium salts have been used with certain success in the management of the following illnesses or conditions. 

Some lithium salts such as H2CO3 are used to treat manic-depressive illness and hyperthyroidism. The manic-depressive therapeutic Li+ concentration range in blood is 0.75-1.25 mM, and it is known that more than 1.5 mM Li+ is toxic and that 3.5-4.5 mM Li+ is lethal. Because of the toxicity of ex-... 

These and other nonreceptor elements of the calcium-phosphoinositide signaling pathway are now becoming targets for drug development. For example, the therapeutic effects of lithium ion, an established agent for treating manic-depressive illness, may be mediated by effects on the metabolism of phosphoinositides (see Chapter 29 Antipsychotic Agents Lithium). 

Prien, R. F., Caffey, E. M., Jr., Klett, C. J. 1973, Prophylactic efficacy of lithium carbonate in manic-depressive illness. Report of the Veterans Administration and National Institute of Mental Health collaborative study group, Arch.Gen.Psychiatry, vol. 28, no. 3, pp. 337-341. 

It is now generally accepted that lithium can impair intellectual function. For example, Shaw et al. (1987) found impairments of memory and hand motor speed on lithium. In Manic-Depressive Illness, a book written wholly from a biopsychiatric perspective, Frederick Goodwin and Kay Jamison (1990) nonetheless concluded that lithium does cause serious cognitive impairments. They summarized much of the literature up to that time and declared,... 

As described in the previous section, azophenol crown 4 (n = 1) shows a characteristic coloration only for Li+ ion among alkali metal ions. After extensive examinations in a number of solvent systems, lithium analytical conditions were determined as shown in Table 2 [18a]. The resulting reddish purple color is very stable and its absorbance is maintained for 10-90 min after developing color. The calibration curve for Li+, in other words, sensitivity is linear from 25-250 ppb. Na+ does not interfere, but K+, Rb+, Ca2+, Sr2+, Ba2+, and Mg2+ interfered in the determination with a similar coloration. This method was applied to the analysis of a commercial pharmaceutical preparation, a lithium carbonate tablet, since the Li2C03 tablet has been used for medical treatment of manic depressive illness [18 b]. On the other hand, the azophenol crown 4 (n = 1) is also useful as a reagent for colorimetric determination of Rb+ and Cs+ [19]. 

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