Ketamine-induced altered states of consciousness: a systematic review of implications for therapeutic outcomes in psychiatric practices.
Kaike Thiê da Costa Gonçalves, Vagner Deuel O de Tavares, Maria Luiza de Morais Barros, Aldielyson Jorge Cavalcante de Brito, Patrícia Cavalcanti-Ribeiro, Fernanda Palhano-Fontes, Marcelo Falchi-Carvalho, Emerson Arcoverde, Rafael Guimarães Dos Santos, Jaime E. C. Hallak, Dráulio Barros de Araújo, Nicole Leite Galvão‐coelho
European Archives of Psychiatry and Clinical Neuroscience October 28, 2024 DOI: 10.1007/s00406-024-01925-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Sample size | 29 |
| Population | Patients with mood disorders (major depressive disorder, bipolar disorder), substance use disorder, and social anxiety disorder |
| Intervention | subcutaneous |
| Topics | Anxiety Depression Esketamine Ketamine Altered states of consciousness |
| Keywords | Bipolar disorder Dissociation Mystical experiences Psychotomimetic effects Substance dependence Ketamine treatment esketamine Ketamine therapy Ketamine-assisted therapy |
| Citations | 5 |
| Key findings | Approximately half of the reviewed studies found a positive association between ketamine's psychoactive effects and therapeutic outcomes, but the relationship remains indeterminate due to high heterogeneity. |
Abstract
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 = 25 studies), a large part of them involve treatment-resistant patients (n = 14 studies), substance use disorder (SUD, n = 3 studies), and social anxiety disorder (SAD, n = 1 study). From all included studies (n = 29), 15 (51.72%) of them identified a positive relation between ketamine-induced altered states of consciousness and clinical outcomes, while 13 studies (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 all three 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 involving mood disorders (n = 25), 12 studies (48%) reported a positive relationship between psychoactive effects and therapeutic response. Others 12 studies (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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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About half of the reviewed studies found a positive association between ketamine's psychoactive effects and therapeutic outcomes, while the rest found no or negative associations, leaving the relationship indeterminate.
Synthesized
Comparable studies
Other systematic reviews and meta-analyses on esketamine for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine for mood disorders, anxiety, and suicidality in children and adolescents: a systematic review. Youth ≤19 years old with mood disorders, anxiety, or suicidality | 2025 | Systematic review | |
| Evaluating the potential risk of ketamine-induced hepatotoxicity in the treatment of mood and anxiety disorders: A systematic review. Patients with mood, anxiety, or related psychiatric disorders receiving therapeutic... | 2026 | Systematic review | n = 1,017 |
| Ketamine/esketamine pharmacotherapy for treatment of anxiety disorders and anxiety symptoms in depression: Systematic review. Patients with DSM-5 anxiety disorders or unipolar/bipolar treatment-resistant depression | 2026 | Systematic review |