The Journal of Clinical Psychiatry Podcast

Dr. Gary W. Small, Director of Behavioral Health Breakthrough Therapies at Hackensack Meridian Health and Professor of Psychiatry and Behavioral Health at the Hackensack Meridian School of Medicine, shares decades of clinical and research insight as he discusses the early detection and treatment of age-related cognitive decline. In this episode, he explores the continuum from normal aging to mild cognitive impairment to dementia, the real-world role of biomarkers, the promise and limits of current pharmacologic options, and the lifestyle interventions—especially aerobic exercise—with the strongest data behind them.
For most patients, cognitive decline unfolds gradually rather than suddenly, and the tools we have to detect it have outpaced the clarity of what to do next. Amyloid and tau assays, PET imaging, and APOE genotyping are increasingly available in primary care, but they raise as many questions as they answer, and disclosure can have real psychological consequences. Emerging evidence points to inflammation as a shared mechanism across many forms of decline, with anti-inflammatory drugs, curcumin, Omega-3s, sleep, and exercise all converging on the same target. Dr. Small frames a pragmatic, patient-centered approach: educate, contextualize tests, rule out reversible causes, treat symptomatically and aggressively when appropriate, and above all, move.
🧠 PROTECT, DON’T REPAIR [05:10]:
“It’s easier to protect a healthy brain rather than try to repair damage once it becomes extensive.”
Dr. Small articulates the case for early detection and prevention that has shaped his entire career.
🔬 TREAT THE PERSON, NOT THE SCAN [23:40]:
“You don’t treat a blood test, you treat a person. The good news with some of these early anti-amyloid drugs—the brain scan looks great. The bad news is, you’re going to forget this conversation.”
Dr. Small urges clinicians to resist reflexive, biomarker-driven treatment and instead anchor decisions in symptoms, goals, and risk–benefit conversations.
🏃 ONE RECOMMENDATION ABOVE ALL [44:50]:
“Physical exercise. There’s no question about it. We have the strongest data on it… Get on the treadmill, or even better, get outside and take a brisk walk or jog.”
Asked for a single, universal recommendation for brain health, Dr. Small is unequivocal.

CHAPTERS:
00:00 - Introducing Dr. Gary W. Small
02:20 - From Math to Metaphysics to Medicine
03:30 - Finding a Path into Psychiatry
04:20 - The Road to Geriatric Psychiatry and the Case for Early Detection
06:10 - Defining the Continuum: Normal Aging, MCI, and Dementia
09:00 - Interpreting Cognitive Complaints and the Weight of Information
12:30 - The Biology of Cognitive Decline and the Role of Inflammation
16:00 - What Is Lost When We Wait, and the Curcumin Story
20:20 - The PCP’s Role in Early Intervention and Lifestyle Counseling
22:10 - Biomarkers and Imaging: From Research Tool to Clinical Reality
25:00 - Biomarker vs. Surrogate Marker
27:20 - Differential Diagnosis and the Brain as a Rheostat
29:30 - Pharmacologic Treatment: Symptomatic vs. Disease-Modifying Drugs
32:40 - Lifestyle Modification and the Evidence for Aerobic Exercise
35:40 - Train, Don’t Strain: Exercising the Mind Socially
37:50 - Knowing When to Refer and Building Specialist Relationships
41:00 - Comorbid Conditions and the Whole-Person Approach
42:40 - Looking Ahead: The Next 5–10 Years
44:20 - The Single Best Recommendation: Physical Exercise
45:30 - Closing Thoughts

Links:
Full transcript and show notes: https://www.psychiatrist.com/jcp/ep14-early-detection-cognitive-decline-gary-w-small/
Journal of Clinical Psychiatry: https://www.psychiatrist.com/jcp/
Dr. Gary W. Small: https://www.hmhn.org/find-a-provider
#CognitiveDecline #AlzheimersDisease #GeriatricPsychiatry #BrainHealth

Dr. Roger S. McIntyre, Professor of Psychiatry and Pharmacology at the University of Toronto, shares groundbreaking insights as he discusses the profound connection between metabolism and mental well-being. In this episode, he explores how GLP-1s treat psychiatric illness and common metabolic comorbidities.
The historical reliance on serotonin, norepinephrine, and dopamine models has proven incomplete, and many individuals with psychiatric illness continue to struggle with inadequate care. New science suggests a deeper connection between metabolism and brain health which challenges long-held beliefs about disease causes. Emerging research highlights how metabolic disruptions contribute to mental health conditions, and that GLP-1 drugs offer a path forward as they could treat mental health conditions and common metabolic problems. In essence, they have the potential to bring about profound improvements in mental health and overall well-being.
⚠️ BEYOND NEUROTRANSMITTERS [07:53]:
"For seven decades, we've really been at this altar of serotonin, norepinephrine and dopamine… That paradigm has been remarkably durable… but it's not been fully explanatory. Most people do not benefit adequately from current treatments."

Explaining why traditional models are incomplete, Dr. McIntyre shows how new science offers hope.
💊 COMBAT MEDICATION SIDE EFFECTS [45:34]:
"Clinicians would be certainly on a reasonable evidentiary base of practice if they were prescribing a GLP-1 to target, for example, clozapine-induced weight gain or clozapine-induced diabetes, that would be reasonable."
Dr. McIntyre offers a proven strategy for mitigating adverse effects of psychiatric medications.
🚀 TRANSFORMING LIFESPANS [01:04:30]:
"GLP-1s… have the potential to transform the health span and the lifespan of people living with mental illnesses by targeting on-label considerations today and potentially targeting the underlying pathophysiology of the brain-based disorder tomorrow. So stay tuned."

Revealing the future of mental health, Dr. McIntyre presents a vision that offers new hope for long-term well-being.
CHAPTERS:
00:00 - Why GLP-1 Drugs Are Transforming Mental Health Research
03:08 - The Career Shift That Linked Metabolism and Mood Disorders
06:45 - Moving Beyond Serotonin to Metabolism
13:18 - How GLP-1 Drugs Influence Brain Function and Neuroplasticity
23:40 - Can GLP-1 Medications Reach the Brain? What the Evidence Shows
32:00 - The Four Key Brain-Protective Effects of GLP-1 Therapies
34:54 - How GLP-1 Reduces Cravings, Addiction, and Food Noise
42:18 - When Clinicians Should Prescribe GLP-1s in Psychiatry Today
53:10 - Safety Risks and Drug Interactions Psychiatrists Must Consider
01:00:57 - The Future of Treatments in Psychiatry
01:04:27 - Summing Up GLP-1s and Mental Health
Links:

Full transcript and show notes: https://www.psychiatrist.com/jcp/ep13-emerging-role-glp-1s-psychiatry-roger-s-mcintyre/

Journal of Clinical Psychiatry: psychiatrist.com/jcp/
Dr. Roger S. McIntyre: https://www.linkedin.com/in/roger-mcintyre-976bb167/
#GLP1Drugs #AddictionTreatment #DepressionTreatment #MentalIllnessPrevention

Dr. A. John Rush, renowned for leading the famous STAR*D depression study, addresses a critical challenge in modern psychiatry: while physicians often rely on their clinical intuition to treat complex depression, new data proves this approach has a significant blind spot. Experience alone can miss the full extent of a patient's suffering, leaving crucial progress untracked.
Dr. Rush reveals a system to fix this clinical blind spot using the psychology of clinical measurement. He explains how doctors can implement simple assessment tools to gather objective data, leading to more precise treatment adjustments. This straightforward method gives physicians the power to see what is truly working and can significantly boost patient remission rates.
🎯 BIGGEST LESSON [12:17]:
"By bringing measurement to the bedside, we bring precision and science. The evidence is very clear right now. We make better decisions about what to do with patients."
🎯 OTHER KEY TAKEAWAYS:
⚠️ THE HIDDEN GAP IN PSYCHIATRIC CARE [8:10]:
"We don't know anything about in what order, in what combination, and by what methodology we implement that 'what'."
Dr. Rush explains why knowing a treatment can work is only half the battle. This is the crucial gap between research and real-world results that most clinicians overlook.
✨ WHY 'PROVEN' TREATMENTS FAIL YOUR PATIENTS [20:45]:
"Does this apply to everybody with depression, no matter how they show up? Absolutely not. That's where it really gets very, very interesting because now we're going from efficacy research to effectiveness research."
Learn the critical difference between a treatment working in a controlled trial versus in your complex, real-world patient population.
⚡ THE LAW OF DIMINISHING RETURNS IN DEPRESSION [34:57]:
"The more steps you take, the problem is, the less likely you are to get into remission. So remission rates were like 35% in the first step, 28% in the second step, 15% in the third step, 15% in the fourth step."
Dr. Rush reveals the stark data from the STAR*D study. Use this critical insight to set realistic expectations with patients about the challenges of treatment-resistant depression.
CHAPTERS:
00:00 - Introducing Dr. A. John Rush
02:20 - Why Dr. Rush Chose Psychiatry & a Career in Clinical Research
05:45 - How Cognitive Therapy Shaped Evidence-Based Psychiatry
07:10 - Strategies, Tactics, and the Research Gap
10:59 - Using AI & Clinical Data to Guide Treatment Decisions
18:39 - Why Clinical Trial Results Don't Match Real-World Patients
22:54 - Pragmatic Trials That Reflect Everyday Psychiatric Practice
30:48 - The STAR*D Trial: Sequencing Treatments for Depression
36:32 - Dose Optimization & Long-Term Depression Recovery
39:56 - Building a Learning Healthcare System in Psychiatry
43:48 - Dr. Rush’s Advice for Researchers and Clinicians
Links:
Full transcript and show notes: https://www.psychiatrist.com/jcp/ep12-bridging-research-reality-mental-health-care-a-john-rush
Journal of Clinical Psychiatry: psychiatrist.com/jcp/
Dr. A. John Rush: https://www.linkedin.com/in/a-john-rush-8aa46042/
American Psychiatric Association (APA) Website: https://www.psychiatry.org/psychiatrists/research/registry
#Psychiatry #ClinicalResearch #Depression

Families expect cognitive decline as a normal part of getting older. We watch relatives lose their memories and accept the loss. Past medical trials regarding Alzheimer's disease failed 99 percent of the time, early signs of brain changes were missed, and precious years for early screening and treatment were lost.
But new science changes this reality. Doctors now use blood tests and brain imaging for accurate diagnosis. They prescribe immunotherapy treatments that clear toxic brain plaques and slow cognitive decline by 30 percent. Dr. Marc Agronin shares his exact methods for geriatric psychiatry and dementia care. Learn how early medical intervention stops memory loss as he reveals his new research.
🎯 PRIMARY DISCOVERY[19:51]:
"Someone goes from thinking, ‘I have a terminal disease,’ to ‘I have a manageable disease and I am going to continue to live and do things.’ Their whole mindset changes."
Dr. Agronin reveals the exact medical advancements that give patients their lives back.
🩺 PRACTICE UPGRADE [30:56]:
"We have all sorts of vital signs we check by routine. We need to have a cognitive vital sign that we check, and something like a Mini-Mental, Montreal Cognitive Assessment, something like that is practical to be done in primary care."
Discover how doctors catch memory loss early with simple annual tests.
✨ MEDICAL MILESTONE [46:29]:
"We see over the 18 months of the studies that the rate of decline in terms of both cognition and function is on average about 30 percent slower. And then we know that after 18 months, it is a very slow rate of reaccumulation."
Hear how new monoclonal antibodies melt away brain plaques and stop memory loss.
CHAPTERS:
00:00 - Meet Alzheimer’s Research Leader Dr. Marc Agronin
01:45 - Why a Career in Geriatric Psychiatry and Dementia Care?
06:17 - Why Alzheimer’s Research Is Entering a Breakthrough Era
08:07 - Why Alzheimer’s Disease Is Rising Worldwide
11:04 - How to Explain Alzheimer’s Diagnosis to Patients and Families
16:11 - The Biggest Scientific Breakthroughs in Alzheimer’s Disease
24:30 - How New Biomarker Guidelines Are Changing Alzheimer’s Diagnosis
29:57 - Why Early Screening for Cognitive Decline Matters
36:13 - Brain Health Habits That May Reduce Alzheimer’s Risk
42:50 - Current Alzheimer’s Medications and How They Help Cognition
45:45 - New Anti-Amyloid Treatments That Slow Alzheimer’s Progression
50:01 - Understanding ARIA Side Effects in Alzheimer’s Immunotherapy
54:09 - Emerging Alzheimer’s Treatments and Future Research Directions
01:02:09 - The Role of Empathy and Person-Centered Dementia Care
Links:
Full transcript and show notes: https://www.psychiatrist.com/jcp/ep11-what-clinicians-should-know-about-alzheimers-treatment-marc-agronin/
Journal of Clinical Psychiatry: psychiatrist.com/jcp/
Dr. Marc Agronin: https://www.marcagronin.com/
Figure referenced at 53:35 comes from Figure 1 in the paper “Alzheimer’s Disease Drug Development Pipeline: 2025.”: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.70098
#AlzheimersResearch #BrainHealth #GeriatricPsychiatry

Psychiatric hospitals admit patients for severe mental illness and high suicide risk every day. While mental health professionals treat acute suicidality during these intense crises, standard depression medications can take weeks to work. Traditional clinical psychiatry often leaves vulnerable patients in danger after hospital discharge. Medical teams need rapid suicide prevention treatments to help stabilize psychiatric inpatients quickly.
Learn about potential improvements to inpatient suicide care as Dr. Brett Jones, Medical Head of the Bipolar Disorder Clinic at Toronto’s Center for Addiction and Mental Health, reveals the results of his research review into the best evidence-based medical interventions.
🎯 KEY EPISODE HIGHLIGHTS:
🛑 RESEARCH BLINDSPOT [10:25]:
"I think there are a lot of studies out there. I was reading, I was seeing the evidence, but the consensus as to what would be the most effective treatment and for whom really wasn't there."
Hear Dr. Jones explain the massive missing piece in psychiatric care.
🧠 CLINICAL BREAKTHROUGH [23:45]:
"Some of the chronotherapy was something I actually didn't know about. That certainly is a low cost intervention. So that's quite promising if it turns out to be effective."
See how simple sleep treatments change inpatient psychiatry.
🛠️ STRATEGIC ACTION [34:50]:
"We showed a good effect with a digital version of DBT… So we're going to look at trying to replicate that in a multicenter study."
Get the exact details on digital therapy for hospital units.
CHAPTERS:
00:00 - Honoring Dr. Nolan Williams
03:07 - Career Path into Psychiatry and Suicide Research
07:59 - Why Inpatient Suicide Treatment Needs Better Evidence
12:59 - Key Limitations in Suicide Intervention Research
14:57 - Ketamine and Rapid Acting Treatments for Suicidality
19:48 - Emerging Treatments Beyond Traditional Depression Care
25:47 - Translating Research into Real World Inpatient Practice
30:38 - Major Research Gaps and Need for Better Clinical Trials
33:04 - Hospitalization as a Critical Window to Prevent Suicide
37:41 - Up Next: Dr. Marc Agronin
Links:
Full transcript and show notes: https://www.psychiatrist.com/jcp/ep10-inpatient-treatment-suicidality-brett-jones/
Journal of Clinical Psychiatry: psychiatrist.com/jcp/
Inpatient Treatment of Suicidality: A Systematic Review of Clinical Trials:
https://pubmed.ncbi.nlm.nih.gov/39832343/
Dr. Brett Jones: https://www.linkedin.com/in/brett-jones-1b308260/?originalSubdomain=ca
Center for Addiction and Mental Health: https://www.camh.ca
University of Toronto Psychiatry: https://psychiatry.utoronto.ca
#AcuteSuicidality #InpatientPsychiatry #ClinicalResearch