A systematic review of 29 studies examined whether the psychoactive effects of ketamine are linked to its therapeutic benefits for psychiatric disorders. About half of the studies (51.72%) found a positive relationship between ketamine-induced altered states of consciousness and clinical outcomes, while 44.83% found no link, and one study found a negative association. For mood disorders like major depressive disorder and bipolar disorder, 48% of studies showed a positive relationship and 48% showed none. All three studies on substance use disorder reported a positive correlation. The authors conclude the relationship remains uncertain due to high variability across studies.
In a small open-label trial of 22 patients with treatment-resistant depression who received seven weekly subcutaneous doses of esketamine, those with elevated baseline C-reactive protein (CRP > 1 mg/L) showed significant reductions in CRP by week 4 and week 8, while patients without inflammation showed no change. By week 8, CRP levels in both groups were comparable. Although the inflammation group had a greater average reduction in depression severity (15.88 points on the MADRS scale versus 11.14 points), this difference was not statistically significant, and changes in CRP did not predict symptom improvement. Larger controlled studies are needed.