Amdi Amdisen

PROPHYLACTIC LITHIUM: DOUBLE BLIND DISCONTINUATION IN MANIC-DEPRESSIVE AND RECURRENT-DEPRESSIVE DISORDERS

Abstract Fifty manic-depressive patients and thirty-four patients with recurrent endogenous depression who had been on open lithium treatment for at least a year took part in double-blind discontinuance studies to compare lithium carbonate and placebo. Within each diagnostic group matched pairs were allocated at random to lithium carbonate or placebo. Relapses occurring first in the lithium partners constituted placebo preferences and those occurring first in the placebo parners lithium preferences. Relapses were recorded when requiring hospital admission or supervision with additional therapy at home. Serum-lithium levels were monitored. The trials terminated in significant preference for lithium both in manic-depressive and in recurrent-depressive disorder; this happened when nine patients in each group had relapsed on placebo and none on lithium. During the whole trial, which lasted five months, twenty-one placebo patients relapsed and none of the lithium patients. Before the trials, patients had been on lithium for up to 7 years; even after this long period there was still risk of relapse on withdrawal of the drug.

Clinically significant side effects of lithium treatment A SURVEY OF 237 PATIENTS IN LONG‐TERM TREATMENT

A group of 237 patients in 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.

Lithium treatment and kidney function A SURVEY OF 237 PATIENTS IN LONG-TERM TREATMENT

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/1. 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.

Lithium treatment and kidney function.: A FOLLOW-UP STUDY OF 237 PATIENTS IN LONG-TERM TREATMENT

Two years after a survey of the kidney function in 237 patients given long‐term lithium treatment the patients were invited for re‐examination. Of 184 patients who came for the reexamination 147 had continued lithium treatment; in 37 patients the treatment had been discontinued. The lithium‐treated patients were compared with a group of 68 manic‐depressive patients who were about to be given prophylactic lithium treatment but who had not yet started.

Lithium treatment regimen and renal water handling: The significance of dosage pattern and tablet type examined through comparison of results from two clinics with different treatment regimens

For many years two Danish psychiatric hospitals have used different lithium treatment regimens. In one, slow-release tablets were given in two daily doses and, in the other, conventional tablets were given in a single daily dose. In both hospitals many patients developed polyuria. Multiple regression analyses with sex, age, treatment duration, serum lithium concentration, and treatment regimen as predictor variables showed that the two treatment regimens did not affect the glomerular filtration rate or the proximal reabsorption differently, but that distal water reabsorption was significantly less affected and polyuria less pronounced in the patients given conventional tablets once daily than in those given slow-release tablets twice daily. The authors are divided among themselves as regards the implications of these findings.

GRAVE LITHIUM INTOXICATION WITH FATAL OUTCOME

Despite considerably increased use of lithium in psychiatry and its being regarded as a very toxic preparation, reports of serious complications following treatment are surprisingly few. The literature only describes a few cases with fatal outcome (Schou et al. 1967, Hawkins et al. 1969). One lithiumtreated patient who suffered myocarditis leading to death is reported (Len Tseng 1971) where the lithium was judged the cause. Disturbances in cardiac rhythm and T-wave changes during lithium treatment have been described (Tangendahl et al. 1972). Hypothyreosis and goiter have also been reported in several cases (Schou et al. 1968, Sedvall et al. 1969). The following case of lithium intoxication with fatal outcome is interesting in view of the investigations and section findings. 4

Patient attitudes towards lithium

ABSTRACT ‐ Many patients discontinue prophylactic lithium treatment against medical advice. Knowledge of patient attitudes towards lithium treatment may help explain and prevent non‐compliant behaviour. One hundred and forty patients given lithium treatment from 2 to 17 years were asked what they found most advantageous about the treatment and what they found most disadvantageous. Seventy‐five per cent of the patients experienced freedom from symptoms and the re‐establishment of social functions in the family and in work as the main benefit of the treatment. Twenty‐five per cent perceived no other advantages than possibly the satisfaction of demands from the family or the doctor. Seventy per cent of the patients considered various somatic and non‐somatic complaints the main disadvantage of lithium treatment and 30% found no disadvantages at all. Psychological and other non‐somatic complaints related to work, training, patient status, and the administration of lithium tablets were almost as frequent as somatic complaints. The advantages and disadvantages perceived by the patients did not necessarily correspond with the physicians perception of good or bad treatment response or the presence of unwanted effects.

DIABETES MELLITUS AS A SIDE EFFECT OF TREATMENT WITH TRICYCLIC NEUROLEPTICS

A diabetogenic effect of chlorpromazine and a few chemically related drugs has been observed in several, short-term studies in animals and also a few in man, but has been mentioned only briefly as a possible side effect of therapeutic, long-term drug administration. The present work is a study of the changes in degree of diabetes, as evaluated with the three-hour oral glucose tolerance test, which have been observed in psychiatric patients during treatment with and after discontinuation of chlorpromazine. Furthermore, the incidence of diabetic changes has been determined in groups of patients treated with tricyclic neuroleptics. Glucose tolerance tests were made repeatedly for several months on a few patients in whom glycosuria developed after chlorpromazine treatment for several years. The patients all showed characteristic diabetic changes, which can be illustrated by data from a 58-year old woman. Fig. 1 shows a number of glucose tolerance tests during various phases of the drug treatment. It is noted that the blood sugar curve is abnormally high during chlorpromazine treatment and considerably lower when the patient is on thioridazine or receives no drug treatment. A clearer picture may be obtained if instead of the full glucose tolerance test a single measure of the degree of diabetic change is plotted against time. The following parameters were investigated and found to show roughly parallel changes: maximum glucose concentration; 2 y2-hr. glucose concentration; 3-hr. glucose concentration; total area (area below the blood sugar curve, cf. fig. 1); and reduced are (area between the blood sugar curve and the fasting blood sugar level). Of these the total area has been considered the most useful, because it

Albumin and Beta2-Microglobulin Excretion in Patients on Long-Term Lithium Treatment

Albumin and beta 2-microglobulin excretions were studied in 85 unselected patients treated with lithium for more than 6 months. In 15 patients a lithium-induced impaired renal concentrating ability was found, 13 of these patients revealed a chronic interstitial nephropathy on renal biopsy. There was no significant increase in albumin excretion, and a markedly increased beta 2-microglobulin excretion was seen in only 1 patient. This study supports the hypothesis that the lithium-induced renal lesion in confirmed to the distal part of the nephron.

Plasma Arginine-Vasopressin, Renal-Concentrating Ability and Lithium Excretion in a Group of Patients on Long-Term Lithium Treatment

Plasma arginine-vasopressin (AVP) was measured before and after 24 h of a 26-hour renal concentration test in 47 patients treated with lithium for 6-180 months (mean 70 months). In 34 of the patients, plasma AVP was also measured before and after a 2- to 4-hour period of water loading, and in 31 of the patients, creatinine, 125iothalamate, 131I-hippuran and lithium clearances were measured. Plasma AVP values were compared to those obtained in 8 healthy controls. Baseline AVP levels were significantly higher in the lithium-treated patients than in healthy controls. During the period of water deprivation AVP values increased significantly and during oral water loading a significant decrease took place, AVP values still being significantly higher in the lithium-treated patients than in the healthy controls. During oral water loading a slight increase in lithium clearance as well as fractional lithium excretion was seen as compared to values obtained during the last 2 h of a renal concentration test. This study demonstrates that antidiuretic hormone production is neither blocked nor inhibited during lithium treatment. The hypothalamic system reacts on water deprivation as well as on water loading. This study supports the notion that the main lithium-induced renal affection is a vasopressin-resistant impairment of renal concentrating ability.