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Lithium augmentation therapy in refractory depression: clinical evidence and neurobiological mechanisms Bauer M; Adli M; Baethge C; Berghofer A; Sasse J; Heinz A; Bschor TCan J Psychiatry 2003[Aug]; 48 (7): 440-8OBJECTIVE: This systematic review examines the evidence and discusses the clinical relevance of lithium augmentation as a treatment strategy for refractory major depressive episodes. It also examines hypotheses on the mode of action of lithium augmentation, with a focus on serotonin (5-HT) and neuroendocrine systems, and proposes recommendations for future research. METHOD: We searched the Medline computer database and the Cochrane Library for relevant original studies published in English from January 1966 to February 2003. The key words were as follows: lithium, augmentation strategies, lithium augmentation, major depression, refractory depression, treatment-resistant depression, neuroendocrinology, and serotonin. RESULTS: Of 27 prospective clinical studies published since 1981, 10 were double-blind, placebo-controlled trials, 4 were randomized comparator trials, and 13 were open-label trials. Five of 9 acute-phase placebo-controlled trials demonstrated that lithium augmentation had substantial efficacy. In the acute-treatment trials, the average response rate in the lithium group was 45%, and in the placebo group, 18% (P < 0.001). One placebo-controlled trial showed the efficacy of lithium augmentation in the continuation-phase treatment. Summarizing the open and controlled data, approximately 50% of patients responded to lithium augmentation within 2 to 6 weeks. Animal studies offer robust evidence that lithium augmentation increases 5-HT neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways. CONCLUSIONS: Augmentation of antidepressants with lithium is the best-documented augmentation therapy in the treatment of refractory depression. Emerging data from animal studies suggest that the 5-HTergic system is involved in the augmentatory effect of lithium.|Animals[MESH]|Antidepressive Agents/*administration & dosage/adverse effects[MESH]|Antimanic Agents/*administration & dosage/adverse effects[MESH]|Brain/*drug effects/physiopathology[MESH]|Clinical Trials as Topic[MESH]|Depressive Disorder, Major/diagnosis/*drug therapy/physiopathology[MESH]|Drug Therapy, Combination[MESH]|Humans[MESH]|Hypothalamo-Hypophyseal System/drug effects/physiopathology[MESH]|Lithium Compounds/*administration & dosage/adverse effects[MESH]|Pituitary-Adrenal System/drug effects/physiopathology[MESH]|Serotonin/*metabolism[MESH]|Synaptic Transmission/*drug effects/physiology[MESH]|Treatment Outcome[MESH] |
