U.S. FDA Approves VRAYLAR® (cariprazine) as an Adjunctive Treatment for Major Depressive Disorder
“A Phase 3 Study 3111-301-001 showed a clinically and statistically significant change from baseline to week six in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score for patients treated with cariprazine at 1.5 mg/day + ADT compared with placebo + ADT. A second registration-enabling study, RGH-MD-75, showed a clinically and statistically significant change from baseline to week eight in the MADRS total score for patients treated with cariprazine at 2-4.5 mg/day (mean dose 2.6 mg) + ADT compared with placebo + ADT.
Cariprazine was generally well tolerated in 6- and 8-week studies. Mean weight change was < 2lbs and ? 3% of patients had a weight increase of ? 7%.
The starting dosage of VRAYLAR is 1.5 mg once daily. Depending upon clinical response and tolerability, the dosage can be increased to 3 mg once daily on Day 15. In clinical trials, dosage titration at intervals of less than 14 days resulted in a higher incidence of adverse reactions. The maximum recommended dosage is 3 mg once daily.
Most common adverse reactions observed in the adjunctive MDD studies (? 5% and at least twice the rate of placebo) were:
Akathisia, nausea, and insomnia at the recommended doses in 6-week, fixed-dose trials
Akathisia, restlessness, fatigue, constipation, nausea, increased appetite, dizziness, insomnia, and extrapyramidal symptoms in one 8-week flexible-dose trial at a titration of less than 14 days”
Potential Treatment for “Brain Fog” in Long COVID Patients: Guanfacine plus NAC
As announced in Yale on December 13, 2022 by Isabella Backman “A new Yale case study finds that two medications used for treating traumatic brain injuries, when taken together, can mitigate and sometimes eliminate the cognitive impairments known as “brain fog,” common among people with persistent COVID-19 symptoms….Individuals with long COVID, sometimes referred to as “long-haulers,” experience symptoms that may persist for weeks, months, or even years after their acute viral infection. While symptoms vary widely, a common complaint among patients is “brain fog”—a colloquial term for significant, persistent cognitive deficits, with consistent impairment of executive functioning and working memory. Long-haulers may experience a lack of mental clarity, poor focus and concentration, memory problems, difficulty with multi-tasking, and more. Brain fog can be debilitating, but there currently are no treatment options that are approved for the condition.
Cold Water Immersion Can Have Benefits
From:
Medscape Staff, December 08, 2022
“Bathing in cold water or ice may cut “bad” body fat and reduce the risk of disorders such as diabetes, but other claims of health benefits are less defined, according to researchers from the Arctic University of Norway and the University Hospital of North Norway.
WHAT TO KNOW:
- Immersion in cold water has a major impact on the body. It elevates the heart rate and has positive effects on brown adipose tissue, a type of “good” body fat that is activated by cold and may protect against obesity and cardiovascular disease.
- Exposure to cold water or cold air also appears to increase the production of the protein adiponectin by adipose tissue. Adiponectin plays a key role in protecting against insulin resistance, diabetes, and other diseases.
- Repeated cold-water immersions by inexperienced as well as experienced swimmers during the winter months significantly increased insulin sensitivity and decreased insulin concentrations.
- Numerous health and well-being claims from regular exposure to the cold, such as weight loss, better mental health, and increased libido, may be explained by other factors, including an active lifestyle, trained stress handling, social interactions, as well as a positive mindset.
- Those seeking to voluntarily practice cold-water emersion need to be educated about possible health risks associated with taking a dip in icy water, which include the consequences of hypothermia, and of heart and lung problems, which are often related to the shock from the cold.”
Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma
Gapp, K. et al. wrote about the “Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma” in Neuropsychopharmacol 41, 2749–2758 (2016).
They “used a mouse model of unpredictable maternal separation combined with unpredictable maternal stress (MSUS) to examine the consequences of traumatic stress on coping behaviors in adulthood and across generations, and the potential contribution of (glucocorticoid receptors) GR. We show that MSUS affects avoidance behaviors and learning in aversive environments in exposed fathers and their male offspring. This is associated with an increase in GR expression in the hippocampus, and with decreased DNA methylation of GR promoter in the hippocampus and in germ cells. We show that transmission of the effects of paternal trauma can be prevented by paternal (environmental enrichment) EE, suggesting a reversibility of these effects.”
Editors Note: Dad’s early environmental adversity alter his response to traumatic stress as an adult, and this can be passed to the next generation via epigenetic changes in DNA methylation, histone and microRNA chemical changes persisting in sperm. If the dad with early life adversity is housed in an enriched environment, he does not have the altered response to stress or the changes in GR, and his offspring do not have the transgenerational alterations in stress responsively. This could probably happen in people if we could only figure out to super good environmental enrichment in those having early life adversity. Having lots of stress as a neonate and then being adopted out to wonderful foster family could be the basis for a naturalistic study of this sort of result.
Lithium is a Lifesaver in Bipolar Disorder
Batya Swift Yasgur MA, LSW reported in Medscape Medical News on November 28, 2022 that “Mood stabilizers protect against suicide and all-cause mortality in patients with bipolar disorder (BD), including natural mortality, with lithium emerging as the most protective agent, new research suggests.
Investigators led by Pao-Huan Chen, MD, of the Department of Psychiatry, Taipei Medical University Hospital, Taiwan, evaluated the association between the use of mood stabilizers and the risks for all-cause mortality, suicide, and natural mortality in over 25,000 patients with BD and found that those with BD had higher mortality.
However, they also found that patients with BD had a significantly decreased adjusted 5-year risk of dying from any cause, suicide, and natural causes. Lithium was associated with the largest risk reduction compared with the other mood stabilizers.“
Intermittent theta burst magnetic stimulation (iTBS) is FDA approved.
As reported in Psych. News:?The Food and Drug Administration (FDA) has cleared the SAINT Neuromodulation System for the treatment of refractory depression in adults, Magnus Medical Inc. (the manufacturer of the product)?announced?Tuesday. SAINT is a?modified form of transcranial magnetic stimulation?(TMS) that compresses weeks of conventional TMS therapy into just five days”. ?Regular TMS takes 20-30 minutes per daily session while iTBS takes about 5 minutes and thus can be applied many times in a single day. ?”As demonstrated in a clinical trial?published?in?The American Journal of Psychiatry, Montgomery-Åsberg Depression Rating Scale (MADRS) scores dropped by 62% among participants following five days of SAINT stimulation compared with a 14% drop among participants receiving sham stimulation. These improvements were sustained over a four-week follow-up.” ?The method was developed by Nolan Williams and he used MRI to best target the site of stimulation
Cannabidiol (CBD) does not make cannabis safer
Amir Englund et al reported in Neuropsychopharmacology in A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios that CBD did not protect against the adverse effect of THC. These included impaired delayed verbal recall ( p?=?0.001) and induced positive psychotic symptoms on the PANSS ( p?=?2.41?×?10–5).
Editors Note: Not only does marijuana impair memory, it is a risk factor the onset of bipolar disorder and schizophrenia. When pot is used by a person with a unipolar or bipolar mood disorder, there are increases in depression and anxiety and an overall less favorable course of illness. If a person with a mood disorder uses heavy amounts of marijuana, they could consider buying N-acetylcysteine (NAC) 500mg and increasing the dose to 1,000mg twice a day within a week as this has been shown to decrease drug use compared to placebo in adolescents and young adults using and abusing pot. Most people who sell pot, are not well-informed about its dangers and just want to make money.
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All future posts will include a rating indicating their potential clinical importance.
These ratings will be:
A – Very important and ready for consideration
B – Clinically important for future consideration
C – May become important in the future
D – Related to neurobiology or theory
Adolescent Delta-9-tetrahydrocannabinol induces long-term neuronal disturbances in dorsal vs. ventral hippocampus
De Felice et al reported in Neuropsychopharmacology (2022) how adolescent THC exposure in a rodent model can induce significant morphological disturbances and glutamatergic signaling abnormalities in the hippocampus. The dorsal hippocampus is critical for cognitive and contextual processing, whereas the ventral region is critical for affective and emotional processing. Adolescent THC exposure induces long-lasting memory deficits and anxiety like-behaviors concomitant with a wide range of differential molecular and neuronal abnormalities in dorsal vs. ventral hippocampal regions.
Editors Note: While these data are in rodents, they provide insights into how THC use in adolescents exerts memory deficits and anxiety-like behavior in adulthood by dysregulation of glutamate signaling in the hippocampus. These data converge with data in humans. The bottom line is: use of marijuana in adolescence is not good for brain function, cognition, and behavior in adulthood.
Mindfulness-Based Stress Reduction Equivalent to Escitalopram for Treatment of Anxiety Disorders
Hoge et al reported in JAMA Psychiatry (2022) that in a randomized clinical trial of 276 adults with anxiety disorders, 8-week treatment with mindfulness-based stress reduction (MBSR) was noninferior to escitalopram. The “MBSR is a manualized 8-week protocol with weekly 2.5-hour long classes, a day-long retreat weekend class during the fifth or sixth week, and 45-minute daily home practice exercises…. Qualified instructors taught the theory and practice of several forms of mindfulness meditation, such as breath awareness (focusing attention on the breath and other physical sensations), a body scan (directing attention to one body part at a time and observing how that body part feels), and mindful movement (stretching and movements designed to bring awareness to the body and increase interoceptive awareness)….Escitalopram was initiated at 10 mg daily orally and increased to 20 mg daily at week 2 if well tolerated or delayed if not.” The investigators concluded that “mindfulness-based stress reduction was a well-tolerated treatment option with comparable effectiveness to a first-line medication for patients with anxiety disorders.”
