Ketamine in Modern Medicine: Antidepressant Breakthrough, Anaesthetic Staple, or Substance of Misuse

Ketamine, originally developed as an aesthetic in the 1960s, has since evolved into a multipurpose agent with significant roles in anaesthesia, analgesia, and psychiatry. Its unique pharmacological profile, particularly as an NMDA receptor antagonist, provides rapid onset and preserves cardiovascular and respiratory functions—making it indispensable in emergency and low-resource settings. In recent decades, ketamine has shown promise as a rapid-acting antidepressant, especially for treatment-resistant depression. The approval of esketamine and exploration of safer analogues, novel delivery systems, and personalized pharmacogenomic approaches represent the forefront of psychiatric innovation. However, ketamine's potential for misuse and long-term cognitive effects remain challenges. This review critically evaluates ketamine’s pharmacodynamics, clinical uses, adverse effects, historical development, and future directions in personalized psychiatric care