Acute Antidepressive Efficacy of Lithium Monotherapy, Not Citalopram, Depends on Recurrent Course of Depression

Studies of the 1970s and 1980s showed lithium monotherapy to be an effective treatment of acute unipolar major depressive disorder (MDD) and hence as a potential alternative to monoaminergic antidepressants.The objective was to conduct the first comparison of a lithium monotherapy with a modern antidepressant in the acute treatment of MDD. Results were compared with citalopram's efficacy as shown in a different but methodologically identical study (including same researchers, same time, and same place).Thirty patients with an acute MDD (Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM IV] I) were treated with lithium monotherapy (study 1) or with citalopram monotherapy (study 2, N = 32) for 4 weeks.Response rates (decrease in Hamilton Depression Rating Scale score >50%) were 50% for lithium and 72% for citalopram (P = 0.12). Citalopram-treated subjects showed a greater decrease in Hamilton Depression Rating Scale scores (significant at 2 weeks). In the lithium study, only patients with a recurrent episode (DSM-IV: 296.3) responded (15/22), as opposed to none of 8 patients with a first/single episode (DSM-IV: 296.2) (P = 0.002). Patients with a single episode responded significantly more often to citalopram than to lithium (P = 0.007). Both drugs were well tolerated. Only one patient (citalopram) terminated the study prematurely owing to adverse effects.Our results do not support the use of lithium as an alternative to SSRI in the treatment of acute MDD. The finding of a better response to lithium in patients with a recurrent depression has not been reported before and warrants replication. The comparison is limited by the lack of a randomized double-blind design.