Is severe wasting in elderly mental patients caused by an excessive energy requirement?

Many chronically ill mental patients show rapid and severe weight loss leading to severe nutritional debilitation. Excessive energy requirements secondary to hypermetabolism or hyperactivity have been proposed as the cause. This hypothesis was tested using the new doubly-labelled water (2H218O) technique to obtain accurate estimates of total energy expenditure (TEE) in 14 such patients. Mean TEE was very low (6.1 +/- 1.3 MJ/day). None of the subjects was in significant negative energy balance when studied. Mean resting metabolic rate (RMR) was lower than predicted from standard equations based on healthy elderly subjects. The energy cost of physical activity plus thermogenesis was also low (1.7 +/- 0.9 MJ/day) in all except one subject. The data refute the initial hypothesis and suggest that negative energy balance may be episodic, perhaps during periods of infection and subsequent recovery.

Antidepressive effect of amitriptyline treatment with plasma drug levels controlled within three different ranges.

Seventy-four depressed patients were treated with amitriptyline for 4-6 weeks. Their doses were individually adjusted to maintain the sum of the plasma levels of amitriptyline (AT) and nortriptyline (NT) within one of three different ranges, randomly allocated. Allowance was made for individual plasma binding of the drugs. In the 50 patients between 25 and 65 years of age, the antidepressive response at low plasma drug levels was somewhat poorer than at medium or high levels, which were equally effective. In this age group an association was found between outcome and the individual rate of AT metabolism, expressed as "reciprocal clearance" (RC), the steady-state plasma concentration of AT plus NT divided by the daily AT dose. Good antidepressive outcome was associated with high RC. The implications of these findings for patient treatment and for the interpretation of other studies are discussed. The 18 patients between 65 and 80 years of age showed no significant differences between the effectiveness of treatment at different plasma drug levels, and no significant associations between outcome and RC.

Arginine vasopressin in manic-depressive psychosis.

Urinary excretions of arginine vasopressin (AVP), sodium, potassium, osmoles and creatinine were measured in three in-patients with bipolar manic-depressive psychosis on at least eight 24-hour periods in each affective phase. Mood and body weight were recorded twice daily. The excretion by each patient of sodium, water and osmoles was greater in mania than during depression. Comparison of electrolytes and osmoles suggested that the increase was due to increased intake of salt and water rather than of total diet. There was a fall of mean AVP excretion during mania, the magnitude of the fall being related to the increase of water throughput. Compared with controls, AVP excretion was high and variable. It did not show the normal relationship to urine osmolality. Days with very high AVP were not associated with any characteristic feature of the other measurements; nor were they confined to any one point in the manic-depressive cycle. AVP does not appear to play a major role in the salt and water changes characteristic of manic-depressive psychosis and we have no evidence of its having any direct relationship to mood changes. We suggest that the observed abnormalities of AVP excretion are another manifestation of the central defect of this disease.

Abnormal indices of nutrition in the elderly: a study of different clinical groups.

Anthropometric and biochemical indices of nutrition were measured in 450 elderly women in six groups spanning a wide range of physical dependency. Data from the group of active subjects living at home was used to derive reference ranges for elderly women. Although the index values of this group did not differ greatly from those seen in young subjects, there were large differences between this and some of the other elderly groups where the frequency of low values was as high as 50% for some parameters. Food intakes were measured in four of the six groups and relationships were found between energy, protein and vitamin C intake and body weight, plasma protein levels and vitamin C concentration, respectively. Our findings suggest that, among elderly women, low levels of nutrient intake make a significant contribution to poor anthropometric and biochemical nutritional status. Improvements in diet should be reflected in the indices measured and might, in turn, have beneficial effects on health.

Nutritional state of elderly women on admission to mental hospital.

Since nutritional deficiencies might worsen the severity of symptoms and prolong the length of illness in non-nutritional disorders, particularly in the elderly, we examined the nutritional status of 216 elderly women newly admitted to a mental hospital. Compared to healthy elderly women, they had lower values for plasma prealbumin, vitamin C, and B vitamins. This was particularly common in senile dementia, and appeared to be the result of inadequate intake of protein or vitamins. Regular hospital diet for one month corrected the very low levels of prealbumin, but supplements were essential to remove deficiency of the water-soluble vitamins. Although vitamin supplements did not influence the length of stay in hospital, we did not exclude the possibility that nutritional deficiencies have a significant effect on the severity of mental illness.

The cause and correction of low blood vitamin C concentrations in the elderly.

Chronically sick elderly women had low intakes and low blood concentrations of vitamin C. Small dietary supplements of vitamin C increased the concentration of vitamin C in their plasma and leucocytes to those found in both the active elderly and the young. These findings confirm that low concentrations of vitamin C in the institutionalized and chronically sick elderly are primarily due to poor intake and can be easily corrected by dietary changes. The case for increasing the intake of vitamin C in these patients is discussed.

Side-effects of lithium at lower therapeutic levels: the significance of thirst.

The prevalence of thirst, subjective polyuria and related side-effects was investigated in 87 patients attending a lithium clinic and in a group of 52 controls. Thirst was surprisingly common, occurring in 67% of patients, in spite of the fact that they had been maintained on relatively low levels of lithium, and was due principally to the lithium rather than to other psychotropic drugs. Urine flow and impaired renal water absorption correlated with the serum lithium level and the length of treatment in the patients, despite the fact that few were clinically polyuric. The pattern of the results confirms previous suggestions that lithium may stimulate the thirst mechanism directly as well as via an increased renal resistance to vasopressin. The possible implications in terms of clinical response are discussed.

The contribution of dietary vitamin D and sunlight to the plasma 25-hydroxyvitamin D in the elderly.

Total plasma 25-hydroxyvitamin D (25-OHD) and its components 25-OHD2 and 25-OHD3 were measured during the winter in young and elderly healthy persons and in elderly women patients in a long-stay mental hospital. The long-stay patients had no exposure to sunlight or other ultraviolet irradiation, but their diet alone maintained an average total 25-OHD level of 16 nmol/l (range, 10.3-26.5 nmol/l), with most values within the ranges observed in the other two groups, although the average value was lower. The plasma 25-OHD2 which is derived exclusively from vitamin D2 in the diet was similar in all three groups and the vitamin D intake was also similar in the two elderly groups. 25-OHD3 is obtained from the diet as well as from the skin and in the elderly patients the diet alone maintained equal concentrations of 25-OHD2 and 25-OHD3. These findings taken together suggest that the diet accounted for 70 per cent of the total 25-OHD in the active elderly in winter compared with 50 per cent in the young subjects. In all our subjects, young or old, the diet was the major source of vitamin D.

Plasma vitamin C concentrations in patients in a psychiatric hospital.

Plasma vitamin C was measured in 885 patients in a psychiatric hospital and in 110 healthy controls. The average value was lower in the patients (0.51 mg/100 ml) than in the controls (0.87 mg/100 ml). Length of stay in hospital had little effect on plasma vitamin C in the patients, but the values were marginally lower in males, females on iron therapy and in those with senile dementia. In the patients, many of whom had been offered a similar diet for several years, age was not associated with a change in plasma vitamin C and this suggests that changes in vitamin C with age that have been reported reflect differences in intake. Few patients had values as low as those found in clinical scurvy (less than 0.1 mg/100 ml), but many (32 per cent) had concentrations below the threshold (0.35 mg/100 ml) at which some detrimental effects on health have been reported.

Withdrawal symptoms from lithium. Four case reports and a questionnaire study.

Evidence from four case reports of heightened anxiety, irritability and emotional lability following withdrawal of lithium was confirmed by a questionnaire survey of 110 defaulters from a lithium clinic: 19 per cent of respondents retrospectively reported these temporary symptoms following withdrawal. The possible mechanisms of such a withdrawal effect are discussed, and a phased withdrawal is advocated in situations where continued clinical benefit from lithium is being evaluated. The questionnaire results also confirm anecdotal evidence that lithium reduces emotional responsiveness. The significance of these findings in terms of the current models of lithium's action is discussed.

The body composition of the chronic mentally ill.

The height and weight were measured and the total fat and fat-free mass were estimated in 1123 patients in a mental hospital. The results were compared with the reported values in healthy persons. The young patients weighed the same as young healthy persons whereas the average weight in the elderly patients was much less than healthy elderly persons. In the elderly women patients, this difference in weight was much greater in those with dementia than in those with affective disorders or schizophrenia. The difference in weight was not related to the duration of stay in hospital, and there was no evidence that it was due to malnutrition. The lower weight may therefore by a marker for those persons likely to need institutional care rather than the result of loss of weight. A minority of the elderly patients, particularly the ill and immobile, had one of the biochemical markers of malnutrition, low plasma concentrations of either albumin or vitamin C or vitamin D. On average, these patients weighed less and had less body fat than the others. These patients may be the high-risk group for nutritional deficiency but there was no evidence that any of them had a clinically significant nutritional problem.

The relationship between plasma lithium and the renal responsiveness to arginine vasopressin in man.

1. Arginine vasopressin (AVP) was measured in morning samples of urine from 58 patients treated with lithium for unipolar or bipolar affective disorders and from 25 healthy control subjects. 2. The AVP excretion rate was increased in the patients treated with lithium and was related to the plasma lithium concentration. The increase in AVP excretion is the result of a renal resistance to AVP so that what has been observed is an effect of lithium in vivo related to its plasma level over the therapeutic range.

Inhibition of in vitro production of aldosterone by manic-depressive sera.

Serum samples from psychiatric patients were added to incubations of rat adrenal cortical cells synthesizing aldosterone. A high proportion of sera from patients with bipolar manic-depressive psychosis inhibited aldosterone production, but chronic in-patients without affective disorders gave few inhibitory sera. Inhibition was greatest in depression, lowest during normal affect. In one patient studied through 11 affective cycles the inhibitor score increased during transitions from mania to depression, showing a significant regression on time. The possible relationship of this in vitro phenomenon to the defect of aldosterone regulation in manic-depressive psychosis is discussed.

Amitriptyline pharmacokinetics. A crossover study with single doses of amitriptyline and nortriptyline.

Six healthy volunteers were given single doses of amitriptyline (AT) and of nortriptyline (NT) separated by at least 10 days. Plasma concentrations of both compounds were measured at intervals for 48 or 72 h. The total areas under the concentration-time curves for the ingested drug were greater for NT, but AT concentrations showed much higher peak values and took more than 12 h to reach the terminal beta phase of elimination. Doses of 50 mg AT produced areas averaging slightly less than half those for 100 mg AT in the same subject, suggesting some saturation of the elimination process. The consumption of a large, fatty meal just before taking the AT tablets had little effect on the plasma drug concentration curves. NT half-lives, measured after ingestion of NT tablets, were used in analysing the production of NT from doses of AT in the same subject. There was a rapid early production, amounting to 30-67% of the total and presumably resulting from the first pass of AT through the liver. NT was then formed continuously at a rate always proportional to the simultaneous rate of AT elimination. The total amount of NT entering the systemic circulation was about one-quarter of the AT dose.