Electroconvulsive shocks (ECS) and ketamine are fast-acting antidepressant treatments whose shared neurobiological mechanisms are explored in this systematic review of animal models of depression. Both interventions consistently increase hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) levels. They also positively affect glutamatergic neurotransmission, astrocyte and neuronal morphology, synaptic density, vasculature, and functional plasticity. Restoration of neuroplasticity may be a common mechanism underlying their antidepressant efficacy. Fewer studies have examined these processes after ECS. Understanding these shared fundamental mechanisms could help develop novel therapeutic approaches for severe depression.
Ketamine and its enantiomers show rapid antidepressant effects for major depressive disorder and bipolar disorder, but responses vary widely. This systematic review of 26 studies (1694 participants) found that ketamine treatment is linked to improved subjective sleep quality. Preliminary evidence suggests that baseline sleep disturbances and early sleep improvements may predict antidepressant response. Some studies also indicate beneficial effects on objective sleep and circadian rhythmicity, but this finding is tentative due to few published articles. The authors call for more research on objective circadian measures and potential synergy with chronotherapies.
In adults with treatment-resistant depression, intranasal esketamine added to an antidepressant does not change the likelihood of experiencing insomnia as a side effect compared with placebo. Across seven randomized trials involving 1,311 patients, insomnia was reported by 7.3% of those receiving esketamine and 6.7% of those receiving placebo, a difference that was not statistically significant. This finding contrasts with earlier reports that esketamine improves insomnia symptoms, possibly because adverse-event reporting does not capture gradual improvements in sleep for patients who often have insomnia at the start of treatment.