Linoleic acid in the treatment of lithium-induced tremor: a pilot trial with negative outcome.
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Biomedical subjects
Publications and source records attributed to M Schou.
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A micromethod of chicken mixed lymphocyte culture is described. In order to test the genetic control of the reaction, lymphocytes from the inbred G-B1 and G-B2 strains were cultured together with lymphocytes of the MHC identical chickens of a segregating population of (G-B1 x G-B2) F2 hybrids. Most of these combinations showed no response, which is in agreement with the major importance of the lymphocyte activating determinants (Lads) being controlled by the B complex (chicken MHC). A few strong reactions of MLC between B identical individuals indicated, however, that chickens in addition may have Lads controlled by genes not closely linked to the B complex.
A group fo 237 patients in a long-term lithium treatment were questioned specifically about five side effects commonly associated with lithium treatment and unspecifically about "other" complaints. About one tenth of the patients did not complain of side effects, two thirds had one or two complaints, and one fourth had three or more. About one half of the patients complained of hand tremor, two thirds of increase thirst, one fifth of weight gain exceeding 10kg, one fifth of diarrhea, and one tenth of edema of legs or face. A few patients had other complaints. For each side effect we analysed whether its presence was significantly associated with such patient and treatment variables as sex, age, duration of the lithium treatment, 12-h serum lithium concentration, type of lithium preparation, and additional medication. Men complained of tremor significantly more often than women. Diarrhea was significantly less frequent in patients given additional treatment with antidepressants. Weight gain was associated with increased thirst and fluid output and with significantly increased blood pressure. None of the other variables distinguished between patients with and without the various complaints. We nevertheless hypothesize that a moderate reduction of the serum lithium level may lead to a lowering of the frequency of some side effects.
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Kidney function has been examined in 237 patients who in the autumn of 1977 were in lithium treatment at the Psychiatric Hospital in Risskov, most of them as outpatients. The average age was 42 years. The patients had been given lithium treatment for 0.5-17 years, mean duration 5 years. The mean lithium dosage was 33 mmol/day and the mean 12-hour serum lithium concentration 0.85 mmol/l. Glomerular filtration rate was assessed through determination of 24-hour creatinine clearance and serum creatinine, in some cases iothalamate clearance. Water excretion was assessed through determination of 24-hour urine volume and in some cases urine osmolality after 26 hours of fluid deprivation. Creatinine clearances, serum creatinine concentrations, and urine volumes were subjected to multiple regression analysis with various clinically relevant predictor variables. Affection of glomerular filtration rate was only moderate and progressed slowly. The data indicate that the risk of renal insufficiency and terminal azotemia is remote even when lithium is given for many years. A large number of the patients had altered water excretion with polyuria or lowered urine concentrating ability or both. Due to the extra fluid loss these patients are apt to develop dehydration, and they may then be in danger of lithium poisoning. We hypothesize that lithium-induced changes of kidney function may become less frequent and less pronounced if patients are maintained at serum lithium levels somewhat lower than those employed in the group studied here. We recommend careful monitoring of serum lithium levels, regular control of kidney function, and extra caution when physical illness or additional drug treatment may lead to disturbance of fluid and electrolyte balance.
A recent study by Kling et al (1978) noted the finding of higher lithium concentrations in serum and brain of rats after an intraperitoneal injection (2 mmol lithium kg-1) of lithium orotate as a slurry than of lithium carbonate in solution. The authors suggested that lithium orotate might offer advantages in the treatment of patients. We repeated the experiments of Kling et al but in addition examined the kidney function of the rats. Glomerular filtration rate and urine flow were markedly lower in rats given lithium orotate than in rats given lithium carbonate, sodium chloride or a sham injection. The renal lithium clearance was significantly lower, the kidney weight and the lithium concentrations in serum, kidney and heart significantly higher after injection of lithium orotate than after injection of lithium carbonate. The higher lithium concentrations could be accounted for by the lower kidney function. It seems inadvisable to use lithium orotate for the treatment of patients.
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Twenty-four manic-depressive artists, in whom prophylactic lithium treatment had attenuated or prevented recurrences to a significant degree, were questioned about their creative power during the treatment. Twelve artists reported increased artistic productivity, six unaltered productivity, and six lowered productivity. The effect of lithium treatment on artistic productivity may depend on the severity and type of the illness, on individual sensitivity, and on habits of utilizing manic episodes productively.
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In our hospital, we are studying the renal function of more than 200 patients under lithium treatment. The glomerular function seems to be affected to a small extent, even by long-term lithium administration, and there have been no instances of progressive deterioration of renal function with azotemia. Most of the patients have impaired water reabsorption with polyuria and polydipsia. This is frequently combined with lowered concentrating ability. Polyuria and lowered concentrating ability are not in themselves life-threatening. However, development of dehydration may lead to lithium poisoning, and patients under lithium treatment should be advised to drink extra fluid under circumstances when the fluid balance may become negative. Further studies are required for definitive recommendations concerning extra monitoring of kidney function and lowering of lithium doses.
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Lithium salts are being widely used for treatment and prophylaxis of bipolar affective disorder (manic-depressive psychosis) and are under investigation in more than 30 other illnesses. The relevant literature has grown from 43 articles published between 1949 and 1964 to nearly 4,000 today. A computer-based lithium librarian program has been developed that provides an up-to-date registry of all lithium references, rapid search capability, constant availability, and easy transferability to identical computer systems located on three continents. References provided by the system are more complete, more rapidly available, and less costly than references obtained from other bibliographic services. This specific response to the rapidly expanding lithium literature provides a model for comprehensive aquisition and searching of other specialized subjects areas needed by clinicians and researchers.
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Renal lithium clearance, tissue lithium levels, serum lithium concentration, and body temperature were determined in rats given lithium alone or combined with haloperidol (0.5-1 mg/kg). A slight increase in serum lithium concentration occurred in one of the three groups given lithium plus haloperidol. Haloperidol failed to affect renal lithium clearance, tissue lithium levels and body temperature. The data do not support the hypothesis that haloperidol exerts an action on lithium pharmacokinetics.