Psilocybin Bests SSRI for Major Depression in First Long-Term Comparison
“MILAN — Psilocybin leads to a better overall outcome in the treatment of moderate to severe major depressive disorder (MDD) than the selective serotonin reuptake inhibitor (SSRI) escitalopram, results of the first long-term comparison of the two treatments suggest.
“This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression,” study investigator Tommaso Barba, PhD, candidate Imperial College London, London, England, said in a press release. “Psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work, and social functioning.”
Findings from the 6-month follow-up study of a phase 2 double-blind, randomized, controlled trial were presented on September 22 at the 37th European College of Neuropsychopharmacology (ECNP) Congress and published simultaneously in The Lancet eClinicalMedicine….The initial single-center study included 59 adults with MDD (mean age, 41 years) who were randomized to receive either psilocybin or escitalopram over a 6-week period. The psilocybin arm (n = 30) received two 25-mg oral doses of psilocybin therapy (PT), and the escitalopram arm (n = 29) received 10-20 mg of daily escitalopram plus two (placebo-like) 1-mg doses of psilocybin (ET). Both groups received psychological support….The researchers conclude that while a short course of SSRIs combined with intensive therapeutic support (around 20 hours) “might be enough to induce sustained antidepressant effects,” patients treated with psilocybin showed greater improvements in general functioning, connectedness, and meaning in life.
Although not reassessed in the follow-up, the initial study showed that adverse events, particularly sexual functioning, favored psilocybin, said Barba.”
Family History of Alcohol Dependence Predicts Antidepressant Response to an NMDA Antagonist
LE Phelps reported in Biol. Psy (2009) that subjects with a family history of alcohol dependence showed significantly greater improvement in MADRS scores compared with subjects who had no family history of alcohol dependence.
They concluded that a family history of alcohol dependence appears to predict a rapid initial antidepressant response to the NMDA receptor antagonist ketamine.
Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia
Kaul, et al noted in Jama Psi (2024) that “In this phase 3, double-blind, randomized, placebo-controlled trial in 256 people with schizophrenia, xanomeline-trospium was associated with a statistically significant and clinically meaningful reduction in Positive and Negative Syndrome Scale total score compared with placebo. Xanomeline-trospium was generally well tolerated; the most common adverse events were primarily gastrointestinal effects, which were mild or moderate in intensity and generally transient in nature.
EMERGENT-3 confirms previously reported clinical trials (EMERGENT-1 and EMERGENT-2) demonstrating that xanomeline-trospium is efficacious and well tolerated in people with schizophrenia experiencing acute psychosis. Xanomeline is a dual M1/M4 preferring muscarinic receptor agonist with no direct D2 dopamine receptor blocking activity. KarXT combines xanomeline with the peripheral muscarinic receptor antagonist trospium chloride with the goal of reducing adverse events due to xanomeline-related peripheral muscarinic receptor activation.”
Bipolar Disorder Patients Respond to Ketamine, Esketamine Treatment
(Reposted from the Yale School of Medicine blog)
A small sample of patients with bipolar disorder displayed noteworthy improvement in their depressive symptoms after being treated with the rapid-acting antidepressant intravenous ketamine and the nasal spray esketamine, according to a new Yale led-study.
The study, published October 2 in the Journal of Clinical Psychiatry, also found that patients were not at higher risk of suffering a manic episode during the acute phase of treatment.
Naltrexone Augmented with Prazosin Is Highly Effective for Alcohol Use Disorder
Murray Raskind, of the VA Northwest Mental Illness Research, Education, and Clinical Center, conducted a translational proof-of-concept randomized controlled trial (RCT) of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans.
“Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD…. In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition.
They concluded: “These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for AUD. They are consistent with preclinical studies in rodent models of AUD and strengthen rationale for an adequately powered definitive RCT. “
Accelerated iTBS Treats Bipolar Depression in 5 Days
Yvette Sheline, of the University of Pennsylvania Perelman School of Medicine, reported that 10 intermittent theta burst stimulations (iTBS) per day for 5 days yielded dramatic improvement in patients with bipolar depression – both immediately after the iTBS as well as at 4 weeks.
Resting-state functional MRI was used to individually target the left dorsolateral prefrontal cortex (dlPFC), the region most anticorrelated with the subgenual anterior cingulate cortex (sgACC).
A DESEASE MODIFYING DRUG, LECANEMAB, IS NOW AVAILABLE FOR ALZHEIMER’S DISEASE
C. H. van Dyck from Yale talked about the diagnosis and treatment of Alzheimer’s dementia.
New brain imaging data have revealed that Lecanemab cannot only highly significantly delay memory decline but also improve PET measures of amyloid and tau. Early illness in those with mild cognitive impairment (MCI) can be detected; results indicate better effects of treatment Lecanemab in those with earlier and milder illness compared to those with more severe illness.
Intramuscular versus Intravenous Ketamine for the Management of Treatment-Resistant Depression and Suicidal Ideation
Cristina Albott of the University of Minnesota Medical School reported relatively similar efficacy of intramuscular versus intravenous ketamine for the management of treatment-resistant depression and suicidal ideation in outpatient settings.
“Intramuscular (IM) delivery represents an underexplored and promising route of administration given its high bioavailability and low cost….Sixty-six patients underwent a series of 7 to 9 IV (n=35) or IM (n=31) administrations of 0.5mg/kg ketamine during a 21-28 day period. Both IV and IM showed similar magnitudes of improvement in depression, but surprisingly only the IM route was associated in a significant improvement in suicidal ideation in a within subjects change.”
“No adverse events occurred throughout the treatment series for either administration route…. This clinical case series provides preliminary support for the effectiveness and safety of IM compared to IV ketamine in TRD. “
GLP-1s Might Decrease the Incidence of Depression and Anxiety
Lisa O’Mary of WebMD wrote: “People taking a popular type of drug for weight loss or to manage diabetes have a lower likelihood of being newly diagnosed with depression or anxiety, according to an analysis of millions of people’s health records.
The findings were published this week by researchers from the electronic health record company Epic. Researchers looked for new diagnoses of depression or anxiety among people who started taking drugs from a class called GLP-1 agonists that can help manage blood sugar or treat obesity by mimicking hormone levels in the body that can affect appetite and blood sugar. Many people who take the drugs experience significant weight loss.
The researchers found that people with diabetes who started taking most versions of GLP-1 agonists were between 11% and 65% less likely to be newly diagnosed with depression than people with diabetes who didn’t take one of the drugs. The greatest reduction in likelihood of a new depression diagnosis was observed among people taking tirzepatide, which is sold under the brand names Mounjaro and Zepbound.”
Vitamin B6 Plus Lithium Helps Ease Mania Symptoms in Patients With Bipolar Disorder
Daily vitamin B6 (40mg/day), but not B1 (100mg/day), as an adjunctive therapy to lithium was associated with the improvement of mood symptoms in hospitalized patients with bipolar disorder experiencing a manic episode, according to a study published in the Journal of Affective Disorders 2024; 345 103-111: Zandifar et al.
