Brain sciences
June 4, 2023
Muhammad Youshay Jawad, Saleha Qasim, Menglu Ni et al.
46 citations
Ketamine shows promise as a treatment for bipolar depression, though evidence remains weak. A scoping review of 10 clinical studies (5 randomized controlled trials and 5 open-label studies) found that ketamine was generally tolerable, with minimal risk of triggering manic or hypomanic episodes, and demonstrated some effectiveness in reducing depressive symptoms and suicidality. The treatment may be particularly useful for patients with treatment-resistant bipolar depression. However, more research is needed to establish ketamine's role in both acute and maintenance treatment phases, and to study its potential for preventing recurrence and suicidal behavior.
Journal of affective disorders
June 15, 2024
Gia Han Le, Sabrina Wong, Sebastian Badulescu et al.
25 citations
A systematic review examined how serotonergic psychedelics (psilocybin, LSD) and ketamine affect brain wave patterns measured by EEG and MEG in people with major depressive disorder, treatment-resistant depression, and healthy controls. Ketamine and psychedelics both increase theta power in depressed individuals. In healthy controls and depressed persons, both drug classes decrease alpha, beta, and delta power. Ketamine also increases gamma power in both groups. Theta power specifically rises in those with major depressive disorder when given psychedelics. The studies varied in patient populations, dosing, and measurement devices. The findings support disease models involving altered network connectivity and may guide future treatment discovery.
Journal of affective disorders
April 1, 2024
Sabrina Wong, Angela T H Kwan, Kayla M Teopiz et al.
19 citations
A systematic review of randomized controlled trials compared the clinical efficacy of psilocybin and esketamine in adults with treatment-resistant depression. 25 mg of psilocybin significantly reduced depressive symptoms at 21 days post-dose, with a number needed to treat (NNT) of 5. Psilocybin-induced nausea had a number needed to harm (NNH) of 5. Fixed doses of esketamine (56 mg and 84 mg) showed significant effects at 28 days post-dose, with NNTs of 7. Esketamine-induced headache, nausea, dizziness, and dissociation had NNHs below 10. The preliminary results may reflect only a small portion of the patient population and require replication and longer-term studies. Both agents showed clinically meaningful NNT estimates and acceptable NNH profiles, underscoring their clinical relevance for treatment-resistant depression.
Journal of psychopharmacology (Oxford, England)
April 1, 2024
Nelson B Rodrigues, David Chen-Li, Joshua D Di Vincenzo et al.
12 citations
Ketamine is a rapid antidepressant for people with treatment-resistant depression, but no reliable predictors of response have been identified. This study examined whether variants in the Val66Met and CYP2B6 genes predicted treatment outcomes in 85 participants with major depressive disorder who received four intravenous ketamine infusions. Participants showed significant overall reductions in depression, suicide, and anxiety, with 25% meeting response criteria and 15% meeting remission criteria. However, neither Val66Met nor CYP2B6 genotypes significantly predicted changes in depressive symptoms, suicidality, anxiety, or dissociation. The findings suggest that single-gene predictors are unlikely to be useful and that a broader genetic approach may be needed.
Psychiatry research
January 1, 2022
Joshua D Di Vincenzo, Orly Lipsitz, Nelson B Rodrigues et al.
11 citations
A small proportion of people with treatment-resistant depression experience clinically significant worsening of symptoms during a course of intravenous ketamine, but the rate is very low—between 1.83% and 5.49% across infusion time points—and similar to that seen with conventional antidepressants. In a retrospective analysis of 164 adults (142 with unipolar depression and 22 with bipolar depression) who received four ketamine infusions over two weeks, no individuals with bipolar depression reported worsening. The findings suggest that symptomatic worsening with ketamine is uncommon, though the study's uncontrolled, single-center design limits certainty.
Psychiatry research
January 1, 2025
David C J Chen-Li, Rodrigo B Mansur, Joshua D Di Vincenzo et al.
6 citations
In a real-world clinic setting, a single ketamine infusion significantly reduced suicidal ideation among 96 adults with treatment-resistant depression, as measured by the Columbia Suicide Severity Rating Scale. The reduction shifted the group average from active toward passive suicidal thoughts. A mediation analysis showed that ketamine's antisuicidal effects are partially independent of its antidepressant effects, suggesting a direct benefit on suicidality beyond mood improvement. The findings support ketamine's effectiveness for suicidal ideation outside controlled clinical trials.
Focus (American Psychiatric Publishing)
October 1, 2023
Farhan Fancy, Nelson B Rodrigues, Joshua D Di Vincenzo et al.
4 citations
Repeated intravenous ketamine infusions significantly reduced depression, suicidal thoughts, and anxiety in patients with treatment-resistant bipolar I/II depression, and improved functioning. In an observational study of 66 patients receiving four infusions over two weeks, depressive symptoms dropped by an average of 6.08 points on the QIDS-SR16 scale. Response rate was 35% and remission rate 20%. Hypomania occurred in only 4.5% of patients, with no mania or psychosis. The findings suggest real-world effectiveness and tolerability of IV ketamine for bipolar depression.
Journal of affective disorders
October 15, 2022
Isak Joneborg, Yena Lee, Joshua D Di Vincenzo et al.
A systematic review of five randomized-controlled trials found that ketamine-assisted psychotherapy (KAP) had a significant positive effect on primary outcome measures for adults with substance use disorders and treatment-resistant depression, but the data is mixed. The single trial examining KAP for treatment-resistant depression found no benefit. The review notes a lack of large, replicated clinical trials and no studies actively examining mechanisms of action. Evidence suggests temporary neural changes caused by ketamine, such as NMDAR inhibition and increased synaptic neuroplasticity, may affect treatment outcomes. Preliminary findings also suggest adjunct psychotherapy, changes in perspective, and spirituality may play a role.