The purpose of the study was to examine the outcome of long-term lithium treatment in consecutively admitted affective disorder patients assigned to high and low serum lithium levels. A total of 91 patients were diagnosed according to DSM-III criteria and randomly allocated to two open treatment groups in which prophylactic lithium was administered in high (serum lithium 0.8-1.0 mmol L-1) and low (serum lithium 0.5-0.8 mmol L-1) doses, respectively. The patients were followed for 2 years or until discontinuation of lithium treatment or readmission to hospital for recurrence of affective illness. The main outcome of the treatment groups was compared with Kaplan-Meier survival curves and by Cox regression analysis. A total of 31 patients (34%) completed 24 months of prophylactic lithium treatment without recurrence and readmission to hospital. In total, 18 patients (20%) suffered a recurrence on lithium, and 42 patients (46%) discontinued lithium or were lost to follow-up. No effect of treatment group was seen, either for the total patient group or for the large subgroup of bipolar patients when analysed separately. A number of patients did not maintain their original assignment to the high serum lithium levels group. The results were analysed both according to assignment and according to actual serum lithium levels. Abuse of alcohol or medication was associated with a poor outcome. Only one third of the patients completed 2 years of lithium prophylaxis successfully. No difference in the protection against recurrences was observed between patients maintained on high and low serum lithium levels.

A cohort of manic-depressive patients given prophylactic lithium treatment were examined before treatment started and at intervals during treatment for up to 7 years. The mean lithium dosage was 23.2 mmol/d and the mean serum lithium concentration 0.68 mmol/l. About 40% of the patients were entirely free of side effects, as compared with 10% among patients treated previously with higher lithium doses and serum lithium concentrations. Tremor complaints were presented by 5% of the patients before and by 15% during lithium treatment. The frequency fell with continued treatment, and after a few years it was not higher than before treatment started. Tremor complaints were positively correlated with age and with the use of neuroleptics and antidepressants. The tremorigenic effects of lithium and antidepressants seemed to potentiate each other. Tremor complaints were more frequent at serum lithium levels over than under 0.7 mmol/l. Body weight increased during the first 1-2 years of lithium treatment and then remained constant. The average gain was 4 kg. Weight gain was positively correlated with the patients' body weight before treatment and with the concurrent administration of antidepressant drugs. The frequency of diarrhea complaints (loose stools, defecation urge) rose from 1% to 6% during the first 6 months of lithium treatment and then leveled off. The frequency rose steeply at serum lithium values over 0.8 mmol/l. During lithium administration about one tenth of the patients had psychological complaints, which might or might not have been caused by the treatment: memory impairment and concentrating difficulty, tiredness and "greyness of life", in a few cases altered taste or lowered libido and potency.