1We examined the case notes of 82 psychiatric out-patients (aged 21-84 years) receiving lithium prophylaxis and with steady-state plasma lithium levels. 2 The mean weight-related daily dose of lithium prescribed decreased by about 50% between the third and eighth decades. 3 The corresponding steady-state plasma lithium levels showed a less marked tendency to decrease, this only being seen in the seventh and eighth decades. 4 In patients aged 50 years or over the daily lithium dose required to give a plasma level of 1 mmol 1-1 (0.50 mmol kg-') was significantly lower than that (0.65 mmol kg-') in patients aged under 50 years (P < 0.005, Student's t-test). In patients aged 70-79 years this dose was 31 % lower than in patients under 50 years. However, interindividual variation was great and it was estimated that age only contributed about 14% to the total interpatient variation. 5Of the 36 patients under 50 years of age, 42% had minor lithium side-effects and 17% were not optimally controlled with lithium. The corresponding figures for the 46 'older' patients were 46% and 28%. 6 Generally the 50% dosage reduction seemed necessary to compensate for an age-related decrease in lithium excretion and to reduce lithium side effects to a level comparable to that acceptable in younger patients.

Disturbances of electrolyte metabolism have frequently been reported in depressive illness. Whether these changes are aetiologically important or secondary to the illness is uncertain. However, the maintenance of sodium and potassium gradients across cell membranes is of vital physiological importance. The distribution of electrolytes across cell membranes is probably responsible for the generation and propagation of impulses in excitable tissue. There is evidence that electrolyte changes are closely associated with alteration in cerebral activity. Margerison et al. (7) reported a significant coefficient of concordance between mean daily urinary sodium potassium ratios, the electroencephalogram mean abundances (8–9 c.p.s.) and word output.

In two randomized double-blind controlled trials on 63 depressed female in-patients subject to recurrent affective disorder (bipolar and unipolar manic-depressive psychosis) lithium was shown to have major acute antidepressant effects. At the end of three weeks lithium produced more uniform improvement than did imipramine; lithium in combination with tryptophan (in the form of Optimax) was superior to tryptophan alone--the latter drug having no discernible antidepressant activity in this group of patients. Lithium did not produce an antidepressant effect until the second and third week of both trials.

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