Suppression of herpes simplex virus infections with oral lithium carbonate--a possible antiviral activity

In vitro studies have shown an inhibitory effect of lithium salts on herpes simplex virus (HSV) replication by mechanisms that interfere with viral DNA synthesis. Moreover, clinical studies have shown that oral lithium carbonate and topical lithium succinate can suppress genital HSV infections in humans. We conducted a randomized, double-blind, placebo-controlled trial of oral lithium carbonate in 11 healthy subjects age 28-65 years (mean +/- SD age 38 +/- 11 years) who had at least four recurrent HSV infections in the year preceding the study. Six patients completed at least 5 months of lithium therapy at a mean (+/-SD) average daily lithium dose of 437 +/- 185 mg (range, 150-900 mg) and an average serum lithium level of 0.56 +/- 0.20 mmol/L. Overall, lithium treatment resulted in a consistent reduction in the mean number of episodes/month, the average duration of each episode, the total number of infection days/month, and the maximum symptom severity. In contrast, treatment with placebo resulted in an increase in three out of the four severity measures. Although the comparisons between the treatment groups did not achieve statistical significance due to the limited sample size, there was a clear "trend" for a reduction in the total monthly duration of all HSV infections with lithium (p = 0.08). Lithium treatment was well tolerated and produced no deleterious effects on renal or thyroid function. These observations lend support to prior observations of an antiviral activity of lithium, and suggest the possibility that oral lithium may represent a safe prophylactic agent in patients with recurrent HSV infections.