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.
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.
Expert Review of Neurotherapeutics
September 21, 2020
Hartej Gill, Barjot Gill, David Chen‐li et al.
62 citations
Psychedelics like psilocybin and MDMA show promise as a new type of therapy for mental health disorders. Evidence suggests they may work with just one dose, produce rapid effects, and be effective for treatment-resistant conditions, possibly serving as a standalone treatment. More clinical trials are needed to test their safety, tolerability, and effectiveness in real-world patient populations.
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 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.
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.