Manic-depressive disorder Lithium

A number of drugs inhibit the antidiuretic actions of vasopressin. Lithium is of particular importance because of its use in the treatment of manic-depressive disorders. Lithium-induced polyuria is usually reversible. Acutely, lithium appears to reduce V -receptor-mediated stimulation of adeny-lyl cyclase. Also, hthium increases plasma levels of parathyroid hormone, a partial antagonist to vasopressin. In most patients, the antibiotic demeclocycline attenuates the antidiuretic effects of vasopressin, probably owing to decreased accumulation and action of cyclic AMP. 

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). 

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. 

Lithium compounds are used in ceramics, lubricants, and medicine. Small daily doses of lithium carbonate are an effective treatment for bipolar (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. 

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. 

Lithium has been effective for maintenance treatment of manic-depressive disorder (Suppes et al. 1991], and some patients find the side-effect profile preferable. Lithium is an option for those with unipolar disease [Prienet al. 1973a]. A consensus conference published in 1985 (NIMH/NIH... 

Baldessarini, R.J., Tondo, L., Hennen, J. Effects of lithium treatment and its discontinuation on suicidal behavior in bipolar manic-depressive disorders. J. Clin. Psychiatry 60 (SuppL 2), 77-84, 111-116, 1999. 

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. 

These and other nonreceptor elements of the calcium-phosphoinositide signaling pathway are of considerable importance in pharmacotherapy. For example, lithium ion, used in treatment of bipolar (manic-depressive) disorder, affects the cellular metabolism of phosphoinositides (see Chapter 29). 

Bipolar affective (manic-depressive) disorder is a frequently diagnosed and very serious psychiatric disorder. Patients with cyclic attacks of mania have many symptoms of paranoid schizophrenia (grandiosity, bellicosity, paranoid thoughts, and overactivity). The gratifying response to lithium therapy of patients with bipolar disorder has made such diagnostic distinctions important. 

Lithium, Li, atomic number 3, is the lightest group 1A metal that should be mentioned as a toxicant because of its widespread use as a therapeutic agent to treat manic-depressive disorders. It is also used in a number of industrial applications, where there is potential for exposure. 

Moncrieff, J. 1995, Lithium revisited. A re-examination of the placebo-controlled trials of lithium prophylaxis in manic-depressive disorder, Br.J.Psychiatry, vol. 167, no. 5, pp. 569-573. 

Q3 Manic depressive disorder involves mood swings, and several agents can be used to stabilize mood lithium carbonate or citrate are often used. There appears to be little difference in the therapeutic usefulness of these two salts. Lithium salts are widely used mood stabilizers. They are useful prophylactically in treating both acute mania and bipolar conditions. 

Lithium and carbamazepine are used in treating manic depressive disorder. 

Baldessarini RJ, Tondo L. Recurrence risk in bipolar manic-depressive disorders after discontinuing lithium maintenance treatment an overview. Chn Drug Invest 1998 15 337-51. 

Dr. J. F. J. Cade, an Australian psychiatrist, first reported on the beneficial use of a lithium compound for a psychiatric disorder, namely, manic behavior in 1949. The early human trials were undertaken after initial experiments on rats, which became quite lethargic after treatment with lithium urate. Fairly large doses were required for treating manic behavior and its use for this disorder has been displaced by organic drugs that carry less risk. His report, however, led to its current nse as a treatment for bipolar affective disorder (also known as manic-depressive disorder). Its use in the United States was curtailed for a decade and a half by the US. Food and Dmg Administration (FDA), which based its decision on incidental poisonings due to overuse of a lithium-based table salt substitute, despite a safe record of controlled psychiatric apphcations in Europe. It has been estimated that by 1985... 

More recently, newer medicines have been used to treat bipolar manic depression disorder. Carbamazepine and valproate are two anticonvulsants that have been particularly useful with patients who do not respond to lithium. These medications also have to be monitored for proper dosages. Antidepressants may be necessary during severe depressive episodes but may push a patient into the manic state. In severe cases, hospitalization and even electroconvulsive therapy (ECT) may be necessary. 

Since its introduction several decades ago for the occasional treatment of "psychotic excitement", lithium is still a mainstay in the treatment and prophylaxis of manic-depressive disorders [1]. The biologic basis for the clinical efficacy of lithium is not completely known. Interestingly, the agent relieves both mania and depression, states which appear to be opposites. Its therapeutic range, however, is narrow, and even at the lowest effective dosage, some unwanted side effects may occur [2]. Serum levels above 1.5 mEq/L often result in acute intoxication, which may... 

A new use for lithium carbonate was discovered in 1949 when John Cade (1912-1980), an Australian physician, found that patients with bipolar disorder benefited from taking the substance. Bipolar disorder is a condition once known as manic-depressive disorder. The condition is characterized by dramatic mood swings. A person can be very happy and carefree one moment, but terribly depressed the next moment. Some patients become so depressed that they commit suicide. Until 1949, there was no effective treatment for bipolar disorder. 

The Affective Disorders Manic Depressive Psychoses Lithium in the Affective Disorders A. Side Effects Chemistry Isotopes of Lithium Inorganic Biochemistry Mechanisms of Action Lithium and the Phosphoinositide Signaling System Lithium and the Cell Membrane A. Sodium-Lithium Exchange Anion Exchange Leak... 

Lithium was introduced by Cade in 1949 for the treatment of acute mania (30). Unfortunately, the serious toxic effects of lithium were first recognized quite independently at about the same time, when lithium salts were used as a substitute for table salt in treatment of hypertension in the United States. Use of Westral, a lithium-containing salt substitute, caused a number of deaths (31,32). This unfortunate coincidence delayed the acceptance of lithium in psychiatry until Schou and others showed that lithium could safely be used in manic depressive disorder at rather lower doses than those used by Cade (33). The therapeutic index, however, is low. After its reluctant acceptance, the spectrum of therapeutic activity claimed for lithium then widened for a time, to include a broad range of psychiatric disorders, including schizophrenia. 

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. 

Finally one particular problem of alkali ion complex specificity of enormous medical relevance should be mentioned, i.e. the finding that lithium is very effective as a psychoactive agent in the treatment of manic-depressive disorders. This finding, first made by Cade320 in 1949, and systematically investigated by Schou and his coworkers321 has stimulated many studies of biological effects of lithium. 

Lithium has the lowest density (0.53 gcm ) of all known metals. It is used in the manufacture of alloys, and in certain glasses and ceramics. Lithium carbonate is used in the treatment of manic-depressive disorders, although large amounts of lithium salts damage the central nervous system. 

The normative lithium requirement of humans is assessed at < 100 tg per day, as all German test subjects of both genders took in between < 100 and > 3500 tg Li per day without showing deficiency symptoms, even at the lowest intake amounts (Anke etal. 1995, 1997b). However, deficiency symptoms may occur in dialysis patients, in kidney failure and in parenteral nutrition. Based on intake data in different countries, Schrauzer (2002) suggested a provisional recommended dietary allowance (RDA) of 1 mg Li per day for a 70-kg adult. Compared with the above intake data, therapeutic effectiveness in the treatment of manic-depressive disorders is achieved at doses of 140 to 280 mg Li per day - about 100 to 300 times higher than RDA (Schou... 

LITHIUM OTHER DRUGS USED IN BIPOLAR (MANIC-DEPRESSIVE) DISORDER... 

Lithium ions, for example, are effective in the treatment of some manic-depressive disorders. 

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