Journal of Affective Disorders
November 1, 2020
R. Mcintyre, Isabelle P. Carvalho, L. Lui et al.
186 citations
Ketamine is a rapid and effective treatment for adults with treatment-resistant depression, but different formulations and routes of delivery vary in effect size. A meta-analysis of studies found that intranasal ketamine or esketamine had a large effect on depression symptoms at 24 hours and again at 7-20 days. Intravenous ketamine or esketamine showed a large but not statistically significant effect at 2-6 days. Oral ketamine had a moderate effect at 21-28 days. No conclusions about which formulation or route is best could be drawn because direct comparisons are lacking. More studies with larger samples are needed, especially for oral ketamine.
Journal of Psychiatric Research
May 1, 2022
Tuyen T. Le, Isabel Pazos Cordero, Muhammad Youshay Jawad et al.
82 citations
Ketamine and its enantiomers show different abuse liability. Preclinical evidence indicates that (R,S)-ketamine and (S)-ketamine carry greater risk for abuse than (R)-ketamine, which at antidepressant-relevant doses in rodents appears safe with minimal liability. In clinical settings, limited studies suggest that single or repeated ketamine administrations under professional control did not lead to misuse, dependence, diversion, or gateway activity in patients with treatment-resistant depression. However, most clinical studies were retrospective and lacked systematic evaluation with validated scales. The review identified 65 eligible studies (55 preclinical, 10 clinical), with only 4 preclinical studies evaluating enantiomer abuse liability.
Expert Opinion on Emerging Drugs
January 2, 2021
Amna Majeed, Jiaqi Xiong, Kayla M. Teopiz et al.
48 citations
A review of preclinical and clinical studies indicates that dextromethorphan (DXM) is well tolerated and shows clinically significant antidepressant effects; DXM combined with bupropion has demonstrated replicated and relatively rapid onset efficacy in adults with major depressive disorder (MDD). Preliminary reports also suggest efficacy in adults with bipolar depression. The combination represents a pharmacokinetic and pharmacodynamic synergy that may account for its rapid action. The authors consider DXM/bupropion a safe, well tolerated, and efficacious treatment option for adults with MDD, and highlight the relevance of glutamate as a treatment target. Priority questions include whether it is uniquely effective across discrete domains of psychopathology and whether it can improve patient-reported outcomes.
Psychiatry Research
March 5, 2023
Kevork Danayan, Noah Chisamore, Nelson B Rodrigues et al.
36 citations
Intravenous ketamine reduced symptoms of depression, borderline personality, suicidality, and anxiety in people with treatment-resistant depression and comorbid borderline personality disorder. In a retrospective analysis of 100 participants, those with borderline personality disorder showed significant improvement, with a reduction of 5.95 points on the Quick Inventory of Depressive Symptomatology and a reduction of 0.64 on the Borderline Symptom List. Both groups with and without borderline personality disorder improved similarly on depression, anxiety, and functionality measures, with no significant difference between groups.
Bipolar Disorders
December 14, 2022
Farhan Fancy, Nelson B. Rodrigues, Joshua D. Di Vincenzo et al.
35 citations
Four intravenous ketamine infusions (0.5–0.75 mg/kg) given over two weeks to 66 patients with treatment-resistant bipolar depression produced significant antidepressant effects, with depressive symptoms decreasing further after each infusion. Suicidal thoughts and anxiety also significantly decreased, and functioning improved. The response rate was 35% and remission rate 20% after four infusions. Treatment-emergent hypomania occurred in only 4.5% of patients, with no cases of mania or psychosis. Repeated doses were well tolerated and associated with greater symptom reduction.
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 Psychopharmacology
May 16, 2023
Noah Chisamore, Kevork Danayan, Nelson B Rodrigues et al.
13 citations
Ketamine infusions led to clinically significant reductions in depression, anxiety, and suicidal thoughts in transitional age youth (ages 18–25) with treatment-resistant depression. In a retrospective analysis of 52 youth matched with a general adult sample (ages 30–60), both groups showed comparable improvements after four infusions over two weeks, with moderate effect sizes and no significant group differences. Adverse effects were mild and transient. The findings suggest ketamine is similarly effective and safe for younger adults as for older adults with treatment-resistant depression.
Psychiatry Research
May 8, 2025
Noah Chisamore, Lee Phan, Roger S McIntyre et al.
7 citations
A review of pre-clinical and clinical studies on non-hallucinatory psychedelics (NHPs) for mood and anxiety disorders found five animal studies showing antidepressant-like effects, assessed via forced swim test and open field test, without the head-twitch response that indicates hallucination. One case report described a patient who inadvertently combined trazodone and psilocybin and experienced potent antidepressant effects without psychedelic effects. These preliminary findings suggest that antidepressant benefits of psychedelics may be separable from hallucinatory effects, providing impetus for rigorous clinical trials in humans.
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.