Lithium is the agent that has shown more efficacy for the treatment of Bipolar Disorder (BD), anyway a single agent isn’t effective to control all aspects of the syndrome.

The mood-stabilizer frequently used, in combination with Lithium, is Valproate which presents different methabolism and side effects. Further both molecules are glycogen synthase kinase-3 (GSK-3b) inhibitors and have synergistic neuroprotective action.

We underline the need to better investigate Lithium and Valproate combination therapy in BD.

Observation of Lithium and Valproate combination therapy in a sample of patients with BD, considering doses and serum levels.

56 patients with BD (mean age 38 ± 0,02), followed at the day hospital of the Psychiatric Clinic, University of Pisa, were studied. Serum levels evaluated at the Section of Pharmacology, Department of Neuroscience, University of Pisa.

We identified 5 comparison groups depending on the dose intake of Lithium (11 subjects: 300 mg /die, 9: 450 mg/die, 19: 600 mg/die, 7: 750 mg/die, 10: 900 mg/die) with increased serum levels of the medication (0.27 mEq/l, 0.37 mEq/l, 0.50 mEq/l, 0.52 mEq/l, 0,70 mEq/l). There are not significant differences between groups related to both, the mean dose intake of Valproate (772 mg/die, 744.4 mg/die, 867.5 mg/die, 821.4 mg/die, 845 mg/die) and its serum levels (45.2 mg/L, 46.6 mg/L, 53.2 mg/L, 47.4 mg/L, 48.4 mg/L).

This study aims to identify the effective dose of Lithium in combination with Valproate able to determine the prevention of relapse in BD patients. The use of the lower dose of Lithium maintaining therapeutic effectivness, means reducing side effects, toxicity and the need for constant monitoring.