Nature Mental Health
October 19, 2023
Theresa R. Lii, Ashleigh Smith, Josephine R. Flohr et al.
94 citations
A single dose of intravenous ketamine given during surgical anesthesia was no more effective than placebo at reducing depressive symptoms in adults with major depressive disorder. The trial randomized 40 patients to receive either ketamine or saline while under anesthesia for routine surgery, ensuring that neither participants, investigators, nor staff knew which treatment was given. Depression severity was measured over three days after infusion. Only about 37% of participants correctly guessed their treatment, indicating successful masking. The results suggest that ketamine's antidepressant effect may be influenced by its psychoactive effects, which complicate placebo-controlled testing.
Journal of Affective Disorders
January 1, 2022
L. Mcinnes, Jimmy J Qian, Rishab Gargeya et al.
60 citations
In a retrospective analysis of 537 patients receiving ketamine intravenous therapy for depression in 178 U.S. community practices, 53.6% showed a response (at least 50% reduction in depression scores) and 28.9% achieved remission within 14-31 days after the induction phase. Among patients with suicidal ideation at baseline, 73.0% reported a reduction. A small portion of patients worsened: 8.4% experienced increased depressive symptoms and 6.0% reported increased suicidal ideation. Response rates were similar across levels of baseline depression severity. Patients who responded had about an 80% chance of sustaining that response at 4 weeks and about 60% at 8 weeks, even without maintenance infusions.
Nature Communications
October 19, 2023
Laura M Hack, Xue Zhang, B. Heifets et al.
20 citations
Ketamine rapidly induces altered states of consciousness, but the neural mechanisms are unclear. In a randomized, placebo-controlled study with nonclinical adults, functional neuroimaging examined brain activity during emotional tasks under placebo, low-dose (0.05 mg/kg), and high-dose (0.5 mg/kg) ketamine. Different dissociative experiences had opposing effects on right anterior insula activity: depersonalization reduced task-evoked activity by 0.39 standard deviations, while dissociative amnesia increased it by 0.32 standard deviations. These findings suggest that specific dissociative states may influence how ketamine affects brain activity, potentially informing treatment responses in depression.
Anesthesiology
September 18, 2020
B. Heifets
3 citations
Ketamine has many properties—analgesic, antidepressant, dissociative anesthetic, and others—making it hard to target for specific clinical uses. In a study of 15 healthy adults, Gitlin et al. tested whether ketamine's pain-relieving and dissociative effects are linked. Participants received a single anesthetic dose of ketamine (2 mg/kg) and rated dissociation and pain from a standardized pneumatic cuff stimulus. Using a statistical method called backward elimination, the authors found that dissociation scores did not predict pain scores, suggesting the two effects arise from independent mechanisms. The study also confirmed that midazolam reduced dissociation without affecting analgesia.