American Journal of Psychiatry
March 17, 2021
R. Mcintyre, J. Rosenblat, C. Nemeroff et al.
694 citations
Ketamine and esketamine are the first non-monoamine-based antidepressants with rapid-onset efficacy for adults with treatment-resistant depression, offering hope to those who do not recover fully with standard antidepressants. However, concerns remain about their safety, tolerability, and appropriate placement in treatment algorithms. An international group of mood disorder experts synthesizes evidence on efficacy, safety, and tolerability, and provides guidance for clinical implementation, including practice parameters at point of care. Areas of consensus and future research directions are discussed.
Med (New York, N.Y.)
March 8, 2024
Joshua D Rosenblat, Shakila Meshkat, Zoe Doyle et al.
97 citations
Psilocybin-assisted psychotherapy (PAP) is feasible for patients with complex, treatment-resistant depression, including those with bipolar II disorder and baseline suicidality. In a randomized trial with 30 adults, those receiving immediate PAP showed greater reductions in depression severity (MADRS) compared to a waitlist control, with a large effect size (Hedge's g = 1.07). Adverse events were transient and no serious adverse events occurred. Repeated doses over six months were associated with further improvement. The findings suggest PAP can be safely delivered to this population and warrants further study.
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.
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 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.
Psychiatry Research
August 15, 2025
Sipan Haikazian, Roger S. McIntyre, Shakila Meshkat et al.
7 citations
Ketamine infusions, given intravenously at sub-anesthetic doses, reduced depression and suicidality scores in patients with treatment-resistant major depressive disorder and treatment-resistant bipolar depression. Improvements from an acute course persisted during maintenance infusions over weeks and months, with no cases of suicidal behavior or addiction. One bipolar patient (4%) experienced an affective switch that stabilized. These results provide preliminary support for the long-term use of maintenance ketamine infusions.
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.