Lithium Augmentation in Depressive Patients Not Responding to Selective Serotonin Reuptake Inhibitors1

Abstract

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.

Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat

“…Lithium is also one of the best documented drugs to add when choosing alternative strategies for non-responder patients (Zall et al 1968;De Montigny 1994;Rouillon and Gorwood 1998;Thase et al 1998;Zullino and Baumann 2001). With respect to efficacy, lithium augmentation has been considered as the first-choice procedure for patients who fail to respond to antidepressant monotherapy (Bauer and Dopfmer 1999).…”

Lithium augmentation therapy in refractory depression?Update 2002

“…Lithium augmentation is generally well tolerated with all classes of antidepressants. The combination of lithium with antidepressants has not been reported to be associated with serious side effects (Rouillon and Gorwood 1998;Zullino and Baumann 2001), and therefore has been recommended by many clinicians for treatment resistant depressed patients (Adli et al 2002, de Montigny 1994, Heit and Nemeroff 1998). …”

“…Lithium has been found to potentiate the therapeutic effects of a broad spectrum of antidepressants, including SSRIs (de Montigny 1994a, Bauer 1995, Baumann et al 1996Zullino and Baumann 2001). Lithium augmentation is generally well tolerated with all classes of antidepressants.…”

Off-label Utilization of Antidepressants

“…Whereas polypharmacy has long been considered a malpractice in earlier studies, it has become increasingly apparent nowadays that psychiatric polypharmacy can have some advantages, i.e., to further improve sleep, have a more potent anxiolytic or sedative effect and to overcome therapy resistances (17,20,22).…”