International Journal of Environmental Research and Public Health
April 17, 2018
Carola Rong, Caroline Park, Joshua D. Rosenblat et al.
116 citations
Ketamine produces rapid antidepressant effects in treatment-resistant depression associated with major depressive disorder and bipolar disorder. Identifying which patients will benefit remains a priority. This review identifies multiple pretreatment predictors of response, including high body mass index, family history of alcohol use disorder, history of suicide, adiponectin and vitamin B12 levels, delta sleep ratio abnormalities, glutamine/glutamate ratio, anterior cingulate cortex activity, the Val66Met BDNF allele, and processing speed. High BMI and family history of alcohol use disorder were the most replicated predictors. A complete pheno-biotype of depression likely to benefit from ketamine is far from complete, though metabolic-inflammatory alterations, especially cognitive impairment, are emerging as possible predictors.
Journal of Clinical Psychopharmacology
December 12, 2015
Yena Lee, Kahlood Syeda, Nadia A. Maruschak et al.
75 citations
A single, low-dose administration of ketamine can rapidly reduce depressive symptoms in adults with treatment-resistant mood disorders and may also have antisuicide effects. The antidepressant effects may be partly mediated by targeting neural circuits involved in executive function and cognitive emotional processing. Pretreatment cognitive function predicts treatment outcomes, suggesting that beneficial effects on cognition could be a proximate mechanism for symptom relief, even though ketamine is known to impair cognitive function. Recent reviews and meta-analyses conclude that ketamine has possible clinical benefits in refractory mood disorders, and its salutary effects, particularly on suicidality, may involve procognitive mechanisms.
Bipolar Disorders
May 14, 2020
Roger S. McIntyre, Orly Lipsitz, Nelson B. Rodrigues et al.
64 citations
Intravenous ketamine reduces anxiety, irritability, agitation, and suicidal thoughts in adults with treatment-resistant major depressive disorder or bipolar disorder. In a retrospective analysis of 201 patients at a community clinic, those with elevated anxiety, irritability, and agitation showed significantly greater improvements in overall depressive symptoms, suicidal ideation, anxiety, irritability, and agitation compared to those without these features, regardless of the number of treatments. The findings suggest IV ketamine may be a rapid treatment option for mood disorder patients with mixed features.
The World Journal of Biological Psychiatry
January 11, 2016
Matthew Cooper, Joshua D. Rosenblat, Danielle S. Cha et al.
40 citations
Ketamine produces rapid antidepressant effects but can cause psychotomimetic and dissociative side effects, raising safety concerns. This narrative review synthesizes strategies to reduce those effects, including altering dose and infusion rate, changing the route of administration, choosing a specific enantiomer, co-administering mood stabilizers or antipsychotics, and using alternative NMDA-modulating agents like lanicemine and GLYX-13. Intranasal administration appears the most promising approach for mitigating dissociative and psychotomimetic effects, but the available studies are limited in number and quality, so further investigation is needed.
Journal of Sleep Research
June 16, 2021
Nelson B. Rodrigues, Roger S. McIntyre, Orly Lipsitz et al.
28 citations
Sleep disturbances are common in treatment-resistant depression (TRD). Intravenous (IV) ketamine improved sleep symptoms, which partially mediated its antidepressant and anti-suicidal effects. In 323 adults with TRD receiving four IV ketamine infusions, self-reported improvements in insomnia, night-time restlessness, hypersomnia, early morning waking, and total sleep partially explained reductions in depression severity. Insomnia, night-time restlessness, early morning waking, and total sleep improvements also mediated reductions in suicidal ideation. Each point improvement in total sleep score was associated with 3.29 times higher odds of achieving response or remission (95% confidence interval 2.00–5.41).
CNS Spectrums
December 10, 2020
Nelson B. Rodrigues, Ashley Siegel, Orly Lipsitz et al.
17 citations
Intravenous (IV) ketamine effectively reduces symptoms of depression, suicidal ideation, anxiety, and anhedonia in adults with treatment-resistant depression, regardless of whether they have previously undergone neurostimulation. In a retrospective analysis of 238 patients, those without prior neurostimulation experienced an average 6.4-point reduction on a depression severity scale, while those with a history of neurostimulation showed a 4.3-point reduction. No significant differences emerged between the groups, indicating that IV ketamine benefits even highly intractable patients.
Psychiatry Research
April 25, 2022
Hartej Gill, Parnian Puramat, Pankti Patel et al.
16 citations
Psilocybin shows promise as a treatment for major depressive disorder (MDD), potentially offering an alternative to conventional therapies. A systematic review of neuroimaging studies found that psilocybin administration decreased amygdala activity and reduced depressive symptoms in two studies involving MDD participants. In healthy populations, changes in functional connectivity and activation of prefrontal limbic structures, particularly the ventral medial prefrontal cortex and amygdala, were observed. However, high methodological heterogeneity across the thirteen included studies—ten in healthy populations and three in MDD participants—limits conclusions. Longitudinal research is needed to clarify psilocybin's long-term effects and sustained therapeutic potential for MDD.