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
Yazen Alnefeesi, D. Chen-Li, Ella Krane et al.
177 citations
Ketamine shows substantial real-world antidepressant effects in treatment-resistant depression, with about 45% of patients responding and 30% achieving remission, based on a systematic review and meta-analysis of 79 studies involving 2665 patients. The effect varies considerably among individuals; more treatment-resistant cases remit less often, but response rates do not differ. The therapeutic benefit does not significantly decline with repeated treatments, indicating that even the most treatment-resistant patients may benefit and that mid-to-long term treatment is effective for many.
Journal of Psychiatric Research
December 11, 2020
Jiaqi Xiong, Orly Lipsitz, D. Chen-Li et al.
122 citations
A meta-analysis of nine randomized controlled trials (197 participants) found that a single dose of intravenous ketamine or intranasal esketamine is associated with large reductions in suicidal thoughts at 2, 4, and 24 hours after administration. The pooled effect size for intravenous racemic ketamine at 24 hours was 1.035, and for intranasal esketamine it was 1.309. No trials of intramuscular, oral, or sublingual ketamine reported anti-suicidal ideation effects suitable for quantitative analysis. The authors suggest that further studies are needed to evaluate these other routes of delivery and to compare formulations.
Neuroscience and Biobehavioral Reviews
November 23, 2020
H. Gill, Barjot Gill, Nelson B Rodrigues et al.
92 citations
About 40% of people with major depressive disorder have cognitive impairments, and those with treatment-resistant depression (TRD) often show such deficits. Ketamine, a rapid-acting antidepressant, may help. A systematic review of five studies found that a single low-dose intravenous infusion (0.5 mg/kg) did not worsen cognitive function. Some studies reported improvements in working memory and visual learning after ketamine treatment, while gains in processing speed and verbal learning occurred only in anxious TRD patients. The evidence suggests ketamine may have pro-cognitive effects in TRD, but more research is needed.
Journal of Psychiatric Research
March 1, 2021
Joshua D. Di Vincenzo, Ashley N. Siegel, Orly Lipsitz et al.
59 citations
Most antidepressant medication trials have focused on adults aged 18-65, leaving gaps in knowledge about older and younger populations. Ketamine shows promise for treatment-resistant depression, but its effects in adolescents and older adults are not well understood. This systematic review of 13 studies found that ketamine produced rapid antidepressant effects (within two weeks) in ten studies, with better results from larger, repeated doses and in open-label rather than blinded settings. Two case reports in adolescents noted rapid anti-suicidal effects. Ketamine appeared safe and well-tolerated in these age groups. However, the small number of studies, high heterogeneity, and generally low quality prevent firm conclusions, and rigorous randomized controlled trials are still needed.
Expert Opinion on Drug Safety
June 15, 2020
Nelson B Rodrigues, R. Mcintyre, Orly Lipsitz et al.
50 citations
Intravenous ketamine is safe and well-tolerated in community-based clinics for treatment-resistant depression. Among 203 patients, fewer than 5% withdrew due to tolerability concerns. Blood pressure increased significantly during infusion, with 44.3% meeting criteria for treatment-emergent hypertension (≥165/100 mmHg), and 12% of those with hypertension required medication. Common adverse events were drowsiness (56.4%), dizziness (45.2%), dissociation (35.6%), and nausea (13.3%). Dissociation severity lessened after the first infusion then plateaued. No patients developed psychosis, mania, or new onset suicidality.
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.
Psychiatry Research
October 1, 2021
Tuyen T. Le, Joshua D. Di Vincenzo, K. Teopiz et al.
26 citations
Psychotic depression, a severe form of major depression with hallucinations or delusions, affects 0.35-1% of people over a lifetime. Current treatments, such as antidepressants combined with antipsychotics or electroconvulsive therapy, often lead to relapse and side effects like tardive dyskinesia. Some case studies suggest ketamine may improve both mood and psychotic symptoms in treatment-resistant patients, but its safety is debated because ketamine can induce psychotomimetic effects. Most clinical trials have excluded these patients, so it remains unknown whether ketamine would worsen psychosis. Future research should include people with psychotic features to determine ketamine's safety and effectiveness.
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.
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.
Journal of Affective Disorders
March 1, 2021
R. Mcintyre, Nelson B Rodrigues, Orly Lipsitz et al.
10 citations
The McIntyre and Rosenblat Rapid Response Scale (MARRRS) is a brief self-report measure of depression symptom severity that is sensitive to change with the rapid-acting antidepressant ketamine. In 64 adults with treatment-resistant depression receiving intravenous ketamine, the MARRRS showed high internal consistency and strong convergent validity with the established 16-Item Quick Inventory Depressive Symptoms Self-Report. The scale detected symptom changes across four infusions and loaded onto two factors: dysphoria and psychic anxiety. The findings suggest that outcome measures validated for rapid-acting treatments are needed to inform treatment progress and decisions.
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.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
February 1, 2025
Danica E Johnson, Nelson B Rodrigues, Sydney Weisz et al.
Depression with co-occurring posttraumatic stress disorder (PTSD) leads to more severe symptoms and poorer response to standard treatments. In a retrospective analysis of 134 patients with treatment-resistant depression, four ketamine infusions (0.5-0.75 mg/kg) reduced depressive symptoms equally in those with and without comorbid PTSD; no significant group-by-time interaction was found. PTSD symptoms also significantly improved across all symptom clusters, with moderate to large effect sizes. Ketamine shows promise as an effective intervention for this hard-to-treat population, though future randomized trials should explore factors driving improvement and long-term outcomes.
Advances in Therapy
April 30, 2021
Eric P. Mcmullen, Yena Lee, Orly Lipsitz et al.
Ketamine can rapidly improve symptoms in adults with treatment-resistant depression, but its effects often last only a median of 2–4 weeks. This systematic review examined strategies to prolong ketamine's acute antidepressant effects. After searching PubMed/MEDLINE, 22 studies were included: 10 randomized controlled trials, 8 open-label trials, 1 retrospective chart review, and 3 case reports. No treatment modality—including pharmacological interventions, psychotherapies, electroconvulsive therapy, or transcranial magnetic stimulation—significantly prolonged the effects of intravenous ketamine, except for repeat-dose IV ketamine itself. Maintenance esketamine is effective in responders. More multimodality strategies are needed.
Journal of Affective Disorders
December 29, 2020
Nelson B Rodrigues, R. Mcintyre, Orly Lipsitz et al.
A 6-item short form of the Clinician-Administered Dissociative States Scale (CADSS-6) strongly correlates with the full 23-item version in patients with treatment-resistant depression receiving IV ketamine. Using retrospective data from 260 patients split into two groups, the CADSS-6 was derived from items most sensitive to ketamine-induced dissociation. Correlations between the short and full scale ranged from 0.91 to 0.95 across four infusions. The CADSS-6 offers a brief clinical assessment for dissociation, though it remains unvalidated in this population and requires prospective validation.