Lithium, for manic depression

Cole N, Parker G. Cade s identification of lithium for manic-depressive fllness -2012 200(12) 1101. ... 

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. 

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... 

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. 

Lithium is not very abundant in the universe, because it is not favored in the nuclear reactions that produce the elements in the stars. Lithium compounds are used in ceramics, lubricants, and medicine. Small daily doses of lithium carbonate have been found to be an effective treatment for manic-depressive disorder but scientists still do not fully understand why. Lithium soaps—the lithium salts of long-chain carboxylic acids—are used as thickeners in lubricating greases for high-temperature applications because they have higher melting points than more conventional sodium and potassium soaps. 

Lithium is rarely used as the only treatment for acute mania, a practical acknowledgment of its limitations. If it is used at all it is combined with a neuroleptic and other sedatives are frequently prescribed as well. Trials comparing effects of lithium and carbamazepine in acute mania reveal that substantial doses of benzodiazepines or barbiturates were used in addition to the study drugs (Freeman et al. 1992 Small et al. 1991). However the belief in lithium s specificity for manic depression means it is still deemed an effective treatment and it is still recommended for mild to moderate cases of mania (National Institute for Clinical Excellence 2006). 

Although it is now widely acknowledged that lithium discontinuation can induce relapse, the full implications of this phenomenon have been avoided. In 2001 the principle American textbook of psychiatry ignored it altogether. It even cited one of the papers that demonstrated the occurrence of withdrawal-related relapse (Suppes et al. 1991) as evidence in support of its recommendation of lifelong drug treatment for manic depression (Marangell et al. 2001, p. 1115). 

Are lithium and other drugs for manic depression useful ... 

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,... 

Lithium has been the treatment of choice for manic-depressive illness for several decades. Lithium is a trace element found in plants, mineral rocks, and in the human body. Today, the major source of medical lithium is mines in North Carolina. Lithium is classified as an antimonic medication because of its ability to reverse mania, a mood disorder characterized by extreme exeitement and activity, hi addition, lithium is also effective in reversing deep depression, the other mood extreme of manic-depressive illness, and in decreasing the frequency of manic and depressive cycles in patients. Manic-depressive illness is now generally referred to as bipolar disorder, a term preferred in the psychiatric community. 

Examples Lithium carbonate is an effective drug for manic-depressive (bipolar) behavior. 

Lithium has unique properties as a treatment for manic depression, but it is by no means the only treatment. Other mood-stabilizing drugs are also prescribed for treatment of the manic phase of the disorder. These drugs are often anticonvulsants such as Depakote (valproate) or sometimes antipsychotic drugs such as Zyprexa (olanzapine). As these drugs are not traditionally thought of as antidepressants, they will not be discussed in detail. 

Pilcher, Helen R. The Ups and Downs of Lithium. Available online. URL www.bioedonline.org/news/news.cfm art=552. Accessed on June 23, 2009. Article explains the pros and cons of lithium use for manic depression and other brain disorders. 

A study in lithium-treated manic-depressive patients foimd that the clearance of lithium was about 20% lower in 23 patients also taking propranolol than in 292 similar patients on lithium alone. However, the clinical effects of this difference were not evaluated, so the significance of this finding is imclear. A 70-year-old man who had been stable on lithium for 16 years was additionally started on propranolol 30 mg daily for lithium-induced tremor. Six weeks later he was hospitalised because of vomiting, dizziness, headache and a fainting episode. His pulse rate was 35 to 40 bpm and his serum-lithium level was 0.3 mmol/L. When later discharged on lithium without propranolol his pulse rate had risen to a range of 64 to 80 bpm. ... 

Lithium is important as the treatment of choice for manic depressive psychosis and this has provoked a wide variety of NMR studies in an endeavour to probe its mode of action. Organolithium compounds are used extensively in synthetic organic chemistry and as industrial catalysts, especially in polymerization reactions. 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

It has been long believed that a lithium ion-selective electrode would render obsolete the flame photometer in the clinical laboratory. Lithium is administered to manic depressive psychiatric patients. Since the therapeutic range (0.5-1.5 mM) is quite close to the toxic range (>2 mM), it must be closely monitored. Most of the iono-phores propo d to date have not met the Li" /Na selectivity required for an interference-free assay. However, it has been reported that calibration in the presence of 140 mMNa permitted the analysis of Li in serum The errors observed are due to fluctuations in the Na concentrations in the sample. More selective ionophores would certainly improve the accuracy of this method. 

Turning to the pharmacotherapy for mania, for decades lithium was the only effective drug treatment. More recently, a number of antiepileptic drugs including carba maze pine, lamotrigine and valproate have been shown to also act as mood stabilisers and are becoming established for the treatment and prophylaxis of both unipolar mania and bipolar manic depressive disorders. 

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. 

The clinical value of lithium has been recognized since 1949. Lithium carbonate is used in manic depressive psychoses for the treatment of recurrent mood changes.261,262 Mood stability may only occur after months rather than weeks. The drug is administered orally in doses up to 2 g day-1 (30 mmol day-1). The serum Li concentration should be in the range of 0.4-0.8 mmol 1. ... 

Detection of Li+ in artificial serum with a voltammetric Li-selective electrode in a flowthrough system was demonstrated [64], Lithium salts such as lithium carbonate have been extensively used for treatment of manic depressive and hyperthyroidism disorders. The therapeutic range of Li concentration is generally accepted to be 0.5-1.5mM in blood serum. The authors used normal pulse voltammetry in which a stripping potential was applied between pulses in order to renew the membrane surface and expel all of the extracted ions from the membrane, similar to galvanostatically controlled potentiometric sensors described above. Unfortunately, the insufficient selectivity... 

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