Lithium salts in the treatment of psychotic excitement.

LITHIUM SALTS enjoyed their hey-day in the latter half of last century when, commencing with their introduction by Garrod, they. were vaunted as curative in gout, and so doubtless in a multitude of other so-called gouty manifestations. This followed the demonstration that lithium urate was the most soluble of the urates. It was shown that if pieces of cartilage with urate deposits were immersed in solutions of sodium, potassium and lithium carbonate, the urate was dissolved first from that piece immersed in the lithium carbonate solution. As time went on and lithia tablets were consumed on an ever-increasing scale for an ever-increasing range of ailments, the toxic and depressant effects were more and more commonly seen. Garrod (1859) wrote of lithium carbonate: "When given internally in doses of from one to four grains dissolved in water, two to three times a day, it produces no direct physiological symptom . their use does not appear to be attended with any injurious consequences. " And certainly, in that dosage, there should never be any toxic symptoms. But about fifty years later cases are reported "of cardiac depression and even dilatation, as a result of excessive and continued consumption of lithia tablets" (The Practitioner, 1907). "Cardiac depression and even dilatation" was perhaps very vague physiology, but the note of warning was clear, also the statement in Squires's "Companion to the British Pharmacopoeia" that "lithia salts upset the stomach very easily" (The Practitioner, 1909). What with the hypothetical cardiac depression and the actual mental depression, nausea and giddiness, the uselessness of lithium in most of the conditions for which it was prescribed, and the fact that there was other, more efficacious treatment in the only disease in which it had been shown to be of some value, it is not surprising that lithium salts have fallen into desuetude. Culbreth (1927) says of lithium bromide that it is the most hypnotic of all bromides. The dosage stated there is the relatively enormous one of 10 to 30 grains. It is not stated how often this huge dose might be repeated each day, but one presumes the traditional two to three times. Squires, too, states that "in epilepsy it is the best of all bromides" and gives the dose more conservatively as five to 15 grains. It is worth noting that the hypnotic action of lithium bromide was thought to be due to the fact that, the atomic weight of lithium being so small, weight for weight, lithium bromide must contain more bromide ion than any other bromide. There is no evidence that the lithium ion was recognized as having a marked sedative action superior in some respects to that of the bromide. But 15 grains of lithium bromide repeated three times a day would soon lead, not to bromide, but to far more dangerous lithium, intoxication, and it is little wonder that it has never found favour in the treatment of epilepsy. It is a pity, because properly used, lithium salts might well be an important addition to the anti-convulsant armamentarium. In the course of some investigations by the writer into the toxicity of urea when injected intraperitoneally into guinea-pigs, it appeared desirable to ascertain whether uric acid enhanced this toxicity. The great difficulty was the insolubility of uric acid in water, so the most soluble urate was chosen--the lithium salt. When an aqueous solution of 8% urea, saturated with lithium urate, was injected, the toxicity was far less than was expected. It looked as if the lithium ion might have been exerting a protective effect. To determine this, more observations were made, lithium carbonate being used instead of lithium urate. An 8% aqueous solution of urea kills five out of ten guinea-pigs when injected intraperitoneally in doses of 1-25 millilitres per ounce of body weight. When 0.5% lithium carbonate in an 8% urea solution was injected in the same dosage, all ten animals survived; and this argued a strong protective function for the lithium ion against the convulsant mode of death caused by toxic doses of urea. …