Dissecting the pro-neurogenic effects of monoaminergic medications used to treat depression: a systematic review and meta-analysis

Abstract

The neurogenic theory of depression proposes that chronic medications modulating monoaminergic neurotransmission may ameliorate symptoms of mood disorders by correcting stressor-induced disruptions in adult hippocampal neurogenesis. However, some controversial findings challenge this assertion. A systematic review and meta-analysis of all pertinent studies, corrected by publication bias, estimated a small, significant, and consistent pro-neurogenic effect of monoaminergic treatments in laboratory rodents. Nearly 30% of the literature exhibited low and 70% unclear risk of bias. In both naïve and stressed mice, pro-neurogenic effects occurred irrespective of strain, sex, stress, or behavioral testing experience. In rats, the effects were predominantly inconclusive due to the lower number of studies in this species. The available number of studies was also insufficient to yield definitive evidence for compounds acting as selective serotonin reuptake inhibitors (citalopram, escitalopram, fluvoxamine), serotonin-norepinephrine reuptake inhibitors (desvenlafaxine, duloxetine, venlafaxine), multimodal monoaminergic modulators (imipramine, desipramine), melatonergic compound (agomelatine), or norepinephrine-serotonin disinhibitory (mirtazapine). Subsequent updates of these reviews appear necessary to establish robust evidence regarding these compounds. Evidence was firm in favor of a robust pro-neurogenic effect of selective serotonin reuptake inhibitor fluoxetine, in both species, making updates of this review probably redundant.