Lithium prophylaxis of manic-depressive disorder: daily lithium dosing schedule versus every second day

The prophylactic efficacy of lithium carbonate given every second day versus daily intake was compared in a double-blind study including 50 manic-depressive patients. The patients met the DSM-III-R criteria for bipolar disorder or depressive disorder; according to ICD-8 the patients fulfilled criteria for manic-depressive disorder: All patients had experienced at least 3 episodes of mania or major depression, and all had been euthymic for at least 4 months. The median doses of lithium carbonate given were 800 mg/day or 1200 mg/every second day corresponding to median 12-h serum lithium concentrations of 0.6 mmol/l or 0.7 mmol/l, respectively. Manic or depressive relapse was defined as DSM-III-R criteria for mania or major depression, and a score > or = 10 on the Bech-Rafaelsen Mania Scale or the Bech-Rafaelsen Melancholia Scale, respectively. The two treatment schedules were allocated at random. Using the Cox proportional hazard model for statistical analysis, the lithium dosing schedule of every second day did not maintain its prophylactic efficacy against recurrent episodes of manic-depressive disorder. The risk of relapse increased 3 times when the interval between intake of lithium was extended from 1 to 2 days.