Rapid-acting antidepressant

A rapid-acting antidepressant is a type of antidepressant drug which improves symptoms of depression 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. These rapid-acting antidepressants are also shown to be effective in patient groups known to have poor response to other antidepressants.[1]

History

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.[2] Benzodiazapine has also presented a potential as a rapid strategy as an antidepressant although worsening moods has also been reported.[3] 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.[4]

Pharmacology

Ketamine

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 in curcial for the antidepressant effects of ketamine.[5]

Side Effects

Ketamine

It has been shown that patients treated for depression with transmucal ketamine show no adverse side effects, though potential interactions with other drugs may cause adverse effects.[6] Patients treated with ketamine intravenously show mild to moderate transient adverse effects including transient perceptual disturbances, dissociation, euphoria, dysphoria, and/or anxiety during infusion.[7] When combined with drugs such as clonazepam, lorazepam, pregabalin, nortriptyline, hydroxyzine, doxepin and trazodone may cause CNS depression. Taking ketamine along with propranolol and doxazosin may cause hypotension, and combining ketamine with lisdexamfetamine and amphetamine/dextroamphetamine will lead to cardiovascular problems.[6] Little is still known about the long-term safety and efficacy of repeated ketamine dosing, which appears to extend the benefits of single ketamine infusions.[7]

List of Rapid-acting Antidepressants

References

  1. ↑ Diazgranados, Nancy (2010). "A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression". Archives of General Psychiatry. 67 (8): 793–802. doi:10.1001/archgenpsychiatry.2010.90. PMC 3000408Freely accessible. PMID 20679587.
  2. ↑ Heal, DJ (2013). "Perspective piece on the history and current use of amphetamine". J Psychopharmacol. 27 (6): 479–96. doi:10.1177/0269881113482532. PMC 3666194Freely accessible. PMID 23539642.
  3. ↑ Dunlop, BW (2008). "Combination treatment with benzodiazepines and SSRIs for comorbid anxiety and depression: a review". Prim Care Companion J Clin Psychiatry. 10 (3): 222–8. doi:10.4088/PCC.v10n0307. PMC 2446479Freely accessible. PMID 18615162.
  4. ↑ Berman, RM (2000). "Antidepressant effects of ketamine in depressed patients". Biol. Psychiatry. 47 (4): 351–4. PMID 10686270.
  5. ↑ Abdallah, Chadi G.; Sanacora, Gerard; Duman, Ronald S.; Krystal, John H. (2015-01-14). "Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics". Annual Review of Medicine. 66 (1): 509–523. doi:10.1146/annurev-med-053013-062946. ISSN 0066-4219. PMC 4428310Freely accessible. PMID 25341010.
  6. 1 2 Ngyuen, Linda (2015). "Off-label use of transmucosal ketamine as a rapid-acting antidepressant: a retrospective chart review". Neuropsychiatr Dis Treat. 11: 2667–2673. doi:10.2147/NDT.S88569. PMC 4610773Freely accessible.
  7. 1 2 Abdallah, Chadi (2015). "Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics". Annual Review of Medicine.
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