Rapid-acting antidepressant

A rapid-acting antidepressant is a type of antidepressant medication which improves symptoms of depression quickly, within minutes to hours. In contrast to rapid-acting antidepressants, conventional antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs), require weeks for their antidepressant effects to manifest.

Euphoriants like amphetamines and opioids produce rapid-acting antidepressant-like effects and were formerly used in the treatment of depression in the early 20th century. However, unlike the case of drugs like conventional antidepressants and ketamine, the antidepressant effects of euphoriants quickly disappear with chronic administration due to tachyphylaxis. Moreover, these drugs show long-lasting depressive effects with long-term use.Benzodiazepines have also presented a potential as a rapid strategy as an antidepressant although worsening moods has also been reported. In the year 2000, it is found that subanesthetic doses of the drug ketamine reduces depressive symptoms within 4 hours of administration in patients with severely treatment-resistant symptoms.

The antidepressant effects of ketamine emerge as a reaction to the acute symptoms of ketamine being metabolized. Ketamine acts as an antagonist of the glutamatergic NMDA receptors, which rapidly increases presynaptic glutamate release while enhancing regional activity in excitatory networks, eventually changing synaptic plasticity and connectivity in the neurons.A low dose of ketamine administration initiates three rapidly consecutive events, a presynaptic disinhibition of glutamatergic neurons, leading to a glutamate surge, an increased activation of the AMPA glutamate receptor and a postsynaptic activation of neuroplasticity-related signaling pathways involving BDNF and mTORC1, which results in overall synaptogenesis and synaptic potentiation. Further evidence in rodent studies shows that AMPA activation is crucial for the antidepressant effects of ketamine.

...
Wikipedia