CNS Drugs
November 17, 2021
Susan Ling, Felicia Ceban, Leanna M.W. Lui et al.
123 citations
Psilocybin, a naturally occurring psychoactive alkaloid found in Psilocybe mushrooms, acts as a non-selective agonist at many serotonin receptors, particularly the 5-HT2A receptor. Its antidepressant and psychedelic effects are thought to involve modulation of the serotonergic system, with downstream changes in gene expression, and indirect effects on dopaminergic and glutamatergic systems. Psilocybin also alters neural circuitry in brain regions implicated in depression, including the default mode network and amygdala. This review synthesizes current understanding of the receptor pharmacology and neuronal mechanisms underlying psilocybin's psychedelic and putative antidepressant properties.
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.
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.
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 3, 2020
Orly Lipsitz, Roger S. McIntyre, Nelson B. Rodrigues et al.
25 citations
Higher body mass index (BMI) does not predict how well patients with treatment-resistant depression respond to intravenous (IV) ketamine. In a study of 230 adults who received four ketamine infusions, people with normal weight, overweight, and obesity (classes I and II) showed similar improvements in depression, suicidal thoughts, anxiety, anhedonia, and daily functioning. The antidepressant effects and rates of partial response, response, and remission were comparable across all BMI groups. The findings are limited by the observational, open-label design of this retrospective analysis.
Journal of Psychopharmacology
October 11, 2020
Roger S. McIntyre, Nelson B. Rodrigues, Orly Lipsitz et al.
19 citations
Adults with treatment-resistant depression or bipolar disorder who also have high anxiety show greater improvement in depressive and anxiety symptoms after intravenous ketamine treatment than those with low anxiety. Among 209 patients receiving four ketamine infusions, the 94 with anxious-distress had a significantly larger drop in depression scores and a greater reduction in anxiety symptoms after three and four infusions. Both groups experienced a significant decrease in suicidal thoughts. The findings suggest that ketamine may be particularly effective for people with treatment-resistant mood disorders and prominent anxiety.
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.
CNS drugs
October 1, 2022
Niloufar Pouyan, Zahra Halvaei Khankahdani, Farnaz Younesi Sisi et al.
16 citations
A systematic review of psilocybin research organized by the Research Domain Criteria (RDoC) framework found that psilocybin has beneficial effects across multiple domains, particularly on positive valence systems, negative valence systems, and social processes. Short-term (23 assessments) and long-term (15 assessments) benefits were reported for positive valence systems. For the negative valence system, 12 outcome measures indicated increased fear, 19 showed no significant effect, and 7 parameters indicated lowered sustained threat over the long term. Thirty-four outcome measures revealed short-term alterations in social systems, including enhanced perception and understanding of others and affiliation. Cognitive systems findings mostly reported dyscognitive effects. Seven studies suggested transdiagnostic effects.
CNS drugs
October 1, 2023
Dania Akbar, Taeho Greg Rhee, Felicia Ceban et al.
A systematic review of five studies found that AXS-05, a combination of dextromethorphan and bupropion, rapidly reduces depression severity in adults with major depressive disorder who do not respond to standard antidepressants. Depressive symptoms measured on the MADRS scale decreased significantly compared to placebo as early as one week and compared to an active control at two weeks. The treatment effect was maintained for up to 12 months, with an average 23-point reduction from baseline. The therapy was well-tolerated with only transient side effects. These results support the role of glutamatergic and sigma-1 signaling pathways in depression.