![]() Unfortunately, the current prognosis for recovery (≥50% depression symptom reduction) from MMD is poor. Statistically, the incidence rate of MDD in the USA is 6.4% of the adult population, of which treatment resistant MMD (TRD) accounts for ~12–20% of that population ( 2). ![]() In addition, annually approximately 800,000 people take their own life. As a major contributor to the overall global burden of disease, MDD has been identified as the leading cause of disability. The World Health Organization ( 1) has declared depression a global epidemic, confirming that over 300 million people suffer from major depressive disorder (MDD) worldwide, a number is increasing exponentially. Such an overview can inform more comprehensive patient care through: (a) informed patient psychoeducation that encompasses all of ketamine's mechanisms of action (b) calibration of optimal dosage to ensure induction and maintenance of high entropy brain states during each ketamine session utilizing EEG measurement (c) Improved management of emergence side effects through proper care for set and setting (d) inclusion of pre-selected appropriate music to enhance the emotional experience (e) increased monitoring of ketamine effects on cortical activity, inter-hemispheric imbalance, and inflammation-related levels of cytokines to further improvements in ketamine protocols and (f) appropriate timing of any adjunctive psychotherapy sessions to coincide with peak neurogenesis at 24–48 h post ketamine treatment. Integrative research that considers these branches of research together may lead toward a better understanding of ketamine's effects and improved treatment protocols and clinical outcomes. Each branch of inquiry has generated independent evidence of ketamine's efficacy but has advanced without substantive coordination or communication with other lines of inquiry. ![]() Much of this research has evolved within the framework of several independent branches of scientific inquiry: in addition to the study of ketamine is a non-selective NMDAR antagonist with rapid antidepressant effects, it has also been found effective as a psychoplastogen that stimulates synaptogenesis and increases neuroplasticity, as a powerful anti-inflammatory that may improve inflammation-related depressive symptoms, as a substance that induces beneficial high entropy brain states, and as a subjectively impactful psychedelic agent. Research over the last two decades has established ketamine as a safe, effective, fast-acting, and sustained antidepressant that significantly reduces adverse symptoms associated with depression, even in patients who are treatment resistant.
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