Lithium augmentation in depressive patients not responding to selective serotonin reuptake inhibitors

This communication reviews current literature on lithium augmentation in patients not responding to SSRIs, giving some recommendations at the end. A significant proportion of depressive patients do not respond to a first antidepressive treatment independently of the class of drugs used. During the last 10 years, there have been several case reports published about open and controlled studies on the use of lithium augmentation in patients who were non-responders to SSRIs, including citalopram, fluoxetine, paroxetine and sertraline. The main underlying hypothesis is a synergistic effect between SSRIs and lithium, which both act on serotonergic neurotransmission. The available studies vary considerably in methodology. There are insufficient results available to confirm a rapid improvement (within 24-48h) after introduction of lithium, but most studies show substantial effects after 1 - 2 weeks, and some after 6 weeks. There is as yet no more clear evidence for a pharmacokinetic interaction between lithium and SSRIs with pharmacodynamic consequences. In conclusion, present evidence suggests that a lithium augmentation in depressive patients who do not respond to SSRIs may be an efficacious and generally well tolerated treatment, with a response rate of at least 50% after a period lasting 1 - 2 weeks. However, special care is indicated when treating elderly patients, where the risk of adverse effects is higher.