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Rapid-Acting Antidepressants.

Jeffrey M Witkin1, Daniel E Knutson2, Gabriel J Rodriguez1

  • 1Witkin Consulting Group, Carmel, Indiana, 46033, United States.

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Summary
This summary is machine-generated.

Rapid-acting antidepressants offer immediate symptom relief, unlike traditional options. Compounds like ketamine and psilocybin show promise for treatment-resistant depression, with some in late-stage development.

Keywords:
GABAA α5KetaminemGlu2/3 receptor antagonistspsychedelicrapid-acting antidepressantsscopolamine.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Psychiatry

Background:

  • Conventional antidepressants target the monoamine hypothesis of depression.
  • Current treatments require weeks for efficacy, posing limitations like non-compliance and suicide risk.
  • There is a critical need for antidepressants with a rapid onset of action.

Purpose of the Study:

  • To review preclinical and clinical findings on compounds that provide immediate symptom relief for depression.
  • To explore novel antidepressant candidates beyond traditional monoamine-targeting drugs.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Analysis of compounds demonstrating rapid antidepressant effects.
  • Examination of proposed mechanisms of action, including AMPA receptor activation.

Main Results:

  • Compounds like ketamine, scopolamine, and psilocybin show rapid antidepressant effects.
  • Novel agents include metabotropic glutamate receptor antagonists and GABA receptor modulators.
  • These agents demonstrate large effect sizes and efficacy in treatment-refractory patients.
  • Potential mechanisms involve glutamate efflux and AMPA receptor activation.

Conclusions:

  • Rapid-acting antidepressants are a major focus in current drug discovery.
  • Ketamine, NMDA receptor antagonists, scopolamine, and psilocybin show promising clinical results.
  • GLYX-13 (Rapastinel) and eskekamine are in late-stage clinical development.