This systematic review aims to elucidate the nexus between ketamine's psychoactive properties and its efficacy in treating a broad spectrum of psychiatric disorders. We searched three databases and used citation tracking to include 29 studies. Predominantly, mood disorders, including bipolar disorder (BD) and major depressive disorder (MDD) (MDD + BD: + n = 25studies), a large part of them involve treatment-resistant patients (n = 14studies), substance use disorder (SUD, n = 3studies), and social anxiety disorder (SAD, n = 1study). From all included studies(n=29), 15 (51.72%) of themidentified a positive relation between ketamine-induced altered states of consciousness and clinical outcomes, while 13studies (44.83%)showed no linkage between them, and one study (3.45%)delineated a negative association. Focusing solely on intravenous (IV) ketamine infusions (n = 25), 14 studies(56%)reported a positive modulation of ketamine's psychoactive effects and therapeutic benefits, whereas 10 studies(40%)confirmed no relationship, and one study (4%)showed a negative association. The single study(33.34%) involving subcutaneous ketamine and allthree studies (66.6%)intranasal administration did not demonstrate a significant interaction between ketamine's psychoactive effects and therapeutic response. All three SUD studies reported a positive correlation between ketamine's psychoactive effects and therapeutic response. In contrast, the single SAD study did not find a relationship between these parameters. For studies involvingmood disorders (n = 25), 12 studies (48%)reported a positive relationship between psychoactive effects and therapeutic response.Others 12studies (48%)identified a null relationship, and one study (4%)found a significant negative association. Although we have found a larger association than previous studies between ketamine's psychoactive properties and its efficacy in treating a broad spectrum of psychiatric disorders, its topic remains indeterminate, mainly due to the high heterogeneity.
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