The Sedating Antidepressant Trazodone Impairs Sleep-dependent Cortical Plasticity

Sara Aton, PhD

Postdoctoral Fellow
Department of Neuroscience
University of Pennsylvania
Philadelphia, Pennsylvania

Although its physiological roles are not completely understood, sleep has demonstrated importance for cognitive processing.1 Sleep is essential for consolidating cortical and synaptic plasticity that occurs during the waking period.2 These complex, dynamic processes ensure normal cognitive functioning, including learning and memory. Thus, factors that affect sleep also influence mechanisms associated with synaptic reorganization and cognition. Hypnotics are one class of medications that promote sleep and likely affect neuronal remodeling. FDA-indicated for the treatment of insomnia, the effects of benzodiazepine receptor agonist (BzRA) hypnotics are well-known. Sedating antidepressants are also often prescribed off-label as hypnotics.3 Trazodone is the most commonly prescribed antidepressant for sleep, which may reflect misperceptions that it is safer and less likely to cause dependence than conventional BzRA hypnotics; it is not scheduled by the US Drug Enforcement Agency; and most or all insomnia is due to depression.4,5 Contributing to these misperceptions is the lack of available data on the effects of sedating antidepressants when used as a hypnotic. Unlike the BzRA and non-BzRA hypnotics, trazodone antagonizes monoaminergic signaling pathways known to regulate synaptic plasticity.6,7 This suggests that in addition to promoting sleep, trazodone may adversely affect normal mechanisms governing sleep-related neuronal remodeling, in turn affecting such processes as learning and memory.

References

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