Ketamine’s Mechanism for Treatment-Resistant Depression

What’s Happening

Interest in ketamine’s potential in medicine continues to grow. Know for its hallucinogenic properties, the substance may be able to treat severe forms of depression that do not respond to other medications. But while clinicians have increasingly recognized ketamine’s strong and fast-acting antidepressant properties, many questions remain regarding how and why it works so quickly and effectively for many individuals.

A new animal model study published in Molecular Psychology attempts to answer these questions by analyzing the multifaceted mechanisms involved. The team, who focused their effort on mice, point out that a possible explanation for the ketamine’s anti-depressive properties could be related to its action on brain receptors that control the release of glutamate (the neurotransmitter associated with depression and stress). Ketamine seems to increase glutamate, which then leads to the release of another neurotransmitter called adenosine. The latter actually stops more glutamate from being released, creating a feedback mechanism that may help to reduce depression and stress reaction.

Why It’s Complicated

Concerns have been raised about the possibility of ketamine causing cognitive impairment. Yet, a systematic review of recent studies has found the opposite–revealing that ketamine use may be associated with improved memory, faster processing speed, and increased ability to switch between mental tasks or activities.

Reports & Perspectives

  • US News &World Report rounds up the results of several studies looking at the benefits of using ketamine to treat challenging cases of depression, achieving improvements in mood quickly, often within 1 day to 1 week.
  • Science Daily reports on the latest findings on ketamine to treat severe depression.
  • The New York Times provides a first-hand look at ketamine through the eyes of a writer with severe depression who finally found relief with ketamine.
  • @NAMIMinnesota (advocacy group) says: “A recent study sheds light on why ketamine may trigger antidepressant effects.”
  • @LJ_Hales (science journalist) shares: “A #ketamine nasal spray will be available to people with severe #depression at select clinics this month as part of a careful rollout of the new therapy – my latest for @Medicalrepublic”
  • @deepak_neuro (neuroanesthesiologist) tweets: “Patients with #depression have worse #postoperative #outcomes including surgical site infection, length of stay & have higher #opioid use. Is #ketamine a potentially effective intervention? @TheBorisLab @stanfordanes at #SNACC2021”

In Practice

ADHD Medications Reduce Suicidality, Improve Cognitive Function in Children

What’s Happening

As many as 6.1 million children and adolescents in the US have ADHD, according to the CDC. Two recent studies shed new light on how to manage the widespread disorder, calling attention to the benefits young people may receive from taking ADHD medication regularly.

One cohort study of 9- to 11-year-olds that appeared on JAMANetwork explores suicidality, which can occur in children with ADHD who strongly exhibit externalizing symptoms. The researchers discovered suicide ideation and attempts declined significantly over the course of 1 year in participants who took ADHD medication over the long term.

A second study in the Journal of Psychiatric Research examined the effects of psychiatric medication on cognitive function in children and adolescents with ADHD between the ages of 6 and 18 years old, many of whom also had autism spectrum disorder or autism traits. The scientists found that cognitive tests scores improved in participants who took a regular dose of ADHD medication, regardless of comorbidities. The researchers used the Wechsler Full Scale IQ and the Index Scales Verbal Comprehension to come to this conclusion.

Why It’s Complicated

Assessing the effectiveness of ADHD medication can be complex since many people with this condition do not take their medication consistently.

Reports & Perspectives

  • The Medical Republic talks about the importance of the study findings on the role of ADHD medication in reducing suicide risk, and also calls on general practitioners to help families get appropriate assessment and treatment.
  • Fox26 Houston reports that the increase in learning delays seen during the pandemic may include adolescents with ADHD that have not yet been diagnosed but may be finding it harder to focus as they get into more advanced work.
  • IACAPAP (International Association for Child & Adolescent Psychiatry and Allied Professions) tweets: #ADHD medication treatment is association with reduced #suicidality – follow up from ABCD cohort. It’s important to recognize the #suicide risk spans beyond depression and across disorders.”
  • @LouThrivingADHD (ADHD advocate and patient) shares: “Another reason why the judgment and stigma [that] surround #ADHD needs to stop. A recent study found ADHD medication not only helps reduce ADHD symptoms in children, it also dramatically lowers the risk of death by suicide.”
  • @LDABC (Learning Disabilities Association of British Columbia) says: “Medication adherence in adolescents may improve cognitive test scores, #ADHD #autism #neurodevelopment”

In Practice

Collaborative Care Reduces Workload for Both Primary and Mental Health Professionals

What’s Happening

With mental health needs among Americans rising and behavioral health clinicians in short supply (burnout anyone?), primary care providers (PCPs) have a valuable opportunity to make a difference. But many clinicians are struggling to figure out how best to support their patients in this area.

To gain insight, researchers led by John C. Fortney at the University of Washington randomly assigned more than 1,000 primary care patients diagnosed with post-traumatic stress disorder (PTSD) and/or bipolar disorder to one of two treatment approaches over a 1-year period. The two approaches used were: Primary care teams providing patients with integrated video mental health treatment in consultation with a mental health professional, and primary care teams referring the patient directly to a psychiatric professional for direct remote treatment visits.

To measure the difference between the two approaches, participants were asked to complete the veterans RAND Health Survey Mental Component Summary (MCS) survey at baseline and again after 12 months of undergoing their assigned treatment method. The findings revealed that both approaches were effective in significantly improving clinical outcomes for participants. Therefore, the researchers recommended in their paper, published in JAMA Psychiatry, that PCPs adapt whichever approach works best for their circumstances and is easiest for them to sustain over the long term.

Why It’s Complicated

While both interventions proved effective, when PCPs took the collaborative approach (ie, video with consultation), they were able to minimize the mental health professional’s time commitment. Thus, a collaborative approach may ultimately help busy mental health professionals serve more patients.

 Reports & Perspectives

  • A recent interview published in BMC Health Services Research reveals that many healthcare policy experts believe video-based behavioral health visits can help bridge the gap between primary and specialty care, but there are policy challenges that need to be overcome for this model to be fully effective.
  • The University of Michigan Health Lab shares a study that finds more than half of patients who have used telepsychiatry during the pandemic prefer to keep using this method even after COVID-19 is no longer such a serious concern.
  • A recent issue of the Journal of Behavioral Health Services and Research includes research that focuses on the lack of mental health services in rural areas and looks at ways to integrate behavioral health care in primary care settings.
  • @Lacktman (chair of legal firm’s telemedicine team) tweets: “This is the first longitudinal study to demonstrate that asynchronous telepsychiatry can improve clinical outcomes in English and Spanish speaking primary care patients…”
  • @PeterYellowlees (Chief Wellness Officer at UC Davis Health) says: “Clinical Outcomes of Asynchronous v Synchronous Telepsychiatry in Primary Care: A Randomized Controlled Trial pubmed.ncbi.nlm.nih.gov/33993104/Changing the way psychiatry is practiced – evidence supporting the use of ATP @PeterYellowlees”
  • @ArrayBC (telepsychiatry provider) shares: “A recent article by mHealth Intelligence is the first longitudal study to demonstrate that asynchrous #telepsychiatry can improve clinical outcomes in English and Spanish speaking primary care patients. #primarycare”

In Practice

Last Updated: Sep 16, 2021