Catching Cognitive Decline Early with Gary W. Small, MD

Bipolar Disorder in Pregnancy and Postpartum, with Crystal T. Clark, MD, MSc

Dr. Crystal T. Clark, Associate Professor of Psychiatry at the University of Toronto and Canadian Research Chair in Reproductive Mental Health, joins the podcast to discuss the evidence-based management of bipolar disorder across pregnancy and the postpartum period. Dr. Clark, recently appointed head of the Department of Psychiatry at Women's College Hospital, has built her research career around closing the pharmacokinetic evidence gap for the mood stabilizers and antipsychotics used during pregnancy. For decades, clinical practice around perinatal bipolar disorder was shaped by stigma and a lack of data, leaving many women counseled to discontinue effective treatment or avoid pregnancy altogether. Dr. Clark reviews how physiological changes in pregnancy alter the clearance of lamotrigine, lithium, and atypical antipsychotics, why postpartum tapering requires close monitoring, how the Mood Disorder Questionnaire can help distinguish bipolar from unipolar postpartum depression, and what her research reveals about racial disparities in diagnosis among Black women. 🎯 KEY EPISODE HIGHLIGHTS: 🚫 THE STIGMA OF DISCOURAGING PREGNANCY [05:30] “No, there's no data. This is all stigma.” Dr. Clark names outright that generations of counseling women with bipolar disorder against having children was never grounded in evidence. 🧪 LAMOTRIGINE CLEARANCE CAN JUMP 300% IN PREGNANCY [16:00] “Elimination clearance really increases during pregnancy as much as two hundred to three hundred percent.” This pharmacokinetic shift explains why patients on a stable lamotrigine dose can relapse mid-pregnancy despite full adherence. 📊 HIGHER BIPOLAR PREVALENCE AMONG BLACK POSTPARTUM WOMEN [48:30] “When you looked at bipolar disorder, there was a higher prevalence amongst Black women.” This diagnosis-level finding, rare in perinatal mental health research, points to a gap in how bipolar disorder is recognized in Black patients. CHAPTERS: 00:00 – Introduction: A Career Built on Closing the Evidence Gap in Perinatal Bipolar Disorder 02:30 – The Discontinuation Era and the Stigma of Childbearing with Bipolar Disorder 08:30 – Reweighing the Risk-Benefit Calculus: Untreated Illness as Its Own Danger 13:30 – From Residency to Research: Uncovering the Pharmacokinetic Evidence Gap 18:00 – The Pharmacology of Pregnancy: How Lamotrigine, Lithium, and Antipsychotics Are Metabolized Differently 22:00 – From Algorithm to Practice: Applying and Titrating Lamotrigine Across Pregnancy and Postpartum 28:30 – Lithium in Pregnancy: Monitoring Levels and Revisiting the Ebstein's Anomaly Risk 35:00 – Atypical Antipsychotics: Quetiapine and Risperidone Pharmacokinetics 40:00 – Distinguishing Bipolar from Unipolar Postpartum Depression with the MDQ 45:30 – Racial Disparities in Perinatal Bipolar Disorder Diagnosis 50:00 – Designing a Postpartum Monitoring Plan for High-Risk Patients 54:00 – Future Directions: Formalizing the Lamotrigine Algorithm and Black Maternal Mental Health Research 57:30 – Closing Reflections: The Path Toward Diagnostic Precision LINKS: Full transcript and show notes: https://www.psychiatrist.com/jcp/ep18-bipolar-disorder-pregnancy-postpartum-crystal-t-clark/ [https://www.psychiatrist.com/jcp/ep18-bipolar-disorder-pregnancy-postpartum-crystal-t-clark/] Journal of Clinical Psychiatry https://www.psychiatrist.com/jcp/ [https://www.psychiatrist.com/jcp/] Publisher of peer-reviewed research discussed in this episode. Dr. Crystal T. Clark – LinkedIn https://www.linkedin.com/in/crystalclarkmd/ [https://www.linkedin.com/in/crystalclarkmd/] Rates of Major Depressive Disorder and Bipolar Disorder in Black and White Postpartum Women (JCP, 2024) https://www.psychiatrist.com/jcp/rates-major-depressive-bipolar-disorder-black-white-postpartum-women/ [https://www.psychiatrist.com/jcp/rates-major-depressive-bipolar-disorder-black-white-postpartum-women/] The 2024 study discussed at length in this episode's chapter on racial disparities in perinatal bipolar diagnosis. A Comparison of Symptoms of Bipolar and Unipolar Depression in Postpartum Women (J Affect Disord, 2022) https://pubmed.ncbi.nlm.nih.gov/35041868/ [https://pubmed.ncbi.nlm.nih.gov/35041868/] The MDQ-based screening study Dr. Clark walks through when discussing how to distinguish bipolar from unipolar postpartum depression. #BipolarDisorder #PerinatalPsychiatry #Psychopharmacology #PostpartumPsychosis #MaternalMentalHealth

The Art of Deprescribing: A Framework for Ending Medication

In this episode, Dr. Ben Everett is joined by Dr. Joseph F. Goldberg, clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai and deputy editor-in-chief of the Journal of Clinical Psychiatry. Dr. Goldberg recently completed his term as president of the American Society of Clinical Psychopharmacology (ASCP), during which he led a 45-member international task force that produced a landmark series of consensus statements on deprescribing psychotropic medications, the principal findings of which were published in JAMA Network Open. The decision to stop a medication is among the most common—yet least formalized—clinical acts in psychiatry. Despite decades of prescribing guidance, the field has lacked systematic frameworks for determining when, why, and how to discontinue treatment. This episode examines the ASCP task force's Delphi methodology, the areas of consensus and expert disagreement, and the practical implications for managing polypharmacy, navigating discontinuation phenomena, counseling pregnant patients, and training the next generation of prescribers. 🎯 KEY EPISODE HIGHLIGHTS: 📋 MEDICINES AS EMPLOYEES: THE PERFORMANCE REVIEW FRAMEWORK [03:30] “I often like to think of medicines like employees on a payroll, and from time to time, it's a good thing to do a performance review of everybody on the payroll and ask what's your job, and are you doing it well, and is your job still there, or is that niche no longer present?” Dr. Goldberg's core framework reframes deprescribing as a structured, periodic clinical evaluation—shifting the default from indefinite continuation to deliberate reassessment. ⚠️ PSEUDOTREATMENT RESISTANCE: THE LAI LITMUS TEST [22:00] “Up to eighty percent of people don't take their medicines as prescribed, and oftentimes that could be quite substantial. It does run the risk of erroneously concluding this drug didn't work for you.” Before deprescribing in schizophrenia, the task force emphasizes ruling out non-adherence—including a strong recommendation to consider long-acting injectable antipsychotics as a diagnostic and therapeutic step. 🧠 THE PSYCHOLOGY OF STOPPING: MEDICATION AS TRANSITIONAL OBJECT [34:30] “To say I'm gonna take away this tangible thing that's meant to alleviate your suffering could mean I think you're doing pretty well and you don't need this anymore. Or it could also mean I'm not sure you're really suffering as much as you think you are.” The decision to deprescribe carries significant psychological weight for patients—and clinicians who overlook this dimension risk undermining therapeutic alliance and triggering distress independent of pharmacology. CHAPTERS: 00:00 – Introduction and Defining Deprescribing 07:00 – Why Now: ASCP's Task Force and the Political Landscape 13:30 – Delphi Methodology: Consensus and Divergence 15:30 – The Lithium Overdose Dilemma: When Stopping Defies a Rule 20:00 – Adherence, Pseudotreatment Resistance, and Schizophrenia 25:30 – Complex Polypharmacy and Medication Performance Reviews 29:30 – Valproate and Women of Reproductive Potential 34:00 – The Psychology of Stopping: Medication Attachment and Placebo 37:30 – Long Half-Life Drugs and Auto-Tapering 40:30 – Discontinuation Phenomena, Brain Zaps, and Hyperbolic Tapering 45:30 – Pregnancy, Special Populations, and Relapse Risk 49:30 – Training Gaps and the Future of Deprescribing Education LINKS: Full transcript and show notes: https://www.psychiatrist.com/jcp/ep17-art-deprescribing-framework-ending-medication-joseph-goldberg/ [https://www.psychiatrist.com/jcp/ep17-art-deprescribing-framework-ending-medication-joseph-goldberg/] Journal of Clinical Psychiatry https://www.psychiatrist.com/jcp/ [https://www.psychiatrist.com/jcp/] Publisher of peer-reviewed research discussed in this episode. Dr. Joseph Goldberg – LinkedIn https://www.linkedin.com/in/joseph-goldberg-922b5317/ [https://www.linkedin.com/in/joseph-goldberg-922b5317/] American Society of Clinical Psychopharmacology (ASCP) https://www.ascpp.org/ [https://www.ascpp.org/] The organization that convened the 45-member international deprescribing task force discussed in this episode. ASCP Deprescribing Consensus Statement — JAMA Network Open https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2845497 [https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2845497] The parent consensus paper on general principles of deprescribing psychotropic medications. #Deprescribing #Psychopharmacology #Polypharmacy #MedicationManagement #ClinicalPsychiatry

Forty Years at the PTSD Frontier with Barbara O. Rothbaum, PhD

EPISODE DESCRIPTION Dr. Barbara O. Rothbaum, PhD, is a tenured professor in the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine, where she holds the Paul A. Janssen Chair in Neuropsychopharmacology. She is director of the Trauma and Anxiety Recovery Program, director of the Emory Healthcare Veterans Program, and as of 2025, science director of the Emory Center for Psychedelics and Spirituality. With more than 400 scientific papers and multiple books to her name, Dr. Rothbaum is one of the foremost authorities on PTSD treatment in the world. In this episode, she joins host Ben Everett to reflect on four decades at the frontier of PTSD research, from the earliest days of the field's recognition as a disorder to the cutting edge of psychedelic-assisted therapy and virtual reality exposure. PTSD remains one of psychiatry's most consequential and undertreated conditions, affecting a substantial portion of combat veterans, survivors of sexual trauma, and countless others who have never received an accurate diagnosis. In this conversation, Dr. Rothbaum covers the evidence base for first-line trauma-focused therapies — prolonged exposure, cognitive processing therapy, and EMDR — and the intensive outpatient model that has dramatically improved treatment retention. She then turns to the stalled landscape of PTSD pharmacotherapy, her translational research combining MDMA with prolonged exposure, the emerging role of psilocybin and ketamine, and the evolution of virtual reality exposure therapy from her laboratory's 1993 pilot to the Brave Mind system now deployed across more than 50 VA health systems. KEY EPISODE HIGHLIGHTS 🧠 PTSD TREATMENT IS ABOUT APPROACHING, NOT AVOIDING [09:00] "There's no way to the other side of the pain except through it." Dr. Rothbaum explains the core mechanism underlying all empirically supported PTSD therapies — and why avoidance is the central obstacle to recovery. 💊 SSRIs ARE NOT REALLY THE TREATMENT FOR PTSD [24:30] "I personally will think of them like weak coffee for PTSD. Maybe you can get a little bit of effect, maybe on mood, maybe on thinking." Despite being the only FDA-approved pharmacotherapy for PTSD, SSRIs fall well short of the evidence base for trauma-focused psychotherapy — and combination treatment offers no advantage. 🥽 VIRTUAL REALITY EXPOSURE THERAPY GIVES CLINICIANS TOTAL CONTROL [43:30] "If my patient's not ready for turbulence, I can guarantee there won't be turbulence. When they are ready for turbulence, I can guarantee there will be turbulence." From fear of heights to virtual Iraq and Afghanistan combat environments, VR allows therapists to precisely calibrate stimulus intensity — closing the gap between imaginal exposure and real-world treatment. CHAPTERS 00:00 - Introduction and Guest Biography 03:30 - Career Origins: Starting with Edna Foa 05:30 - A Career at the Intersection of Therapy, Technology, and Pharmacology 08:00 - First-Line Psychotherapies: PE, CPT, and EMDR 13:30 - Comparing the Therapies: Evidence and Patient Fit 15:30 - The Emory Healthcare Veterans Program and the IOP Model 21:00 - Recognizing PTSD in Primary Care 23:30 - Pharmacotherapy: The Limits of SSRIs 27:30 - Recent Drug Development Setbacks: MDMA and Brexpiprazole 31:00 - Translational MDMA Research and Combining with Prolonged Exposure 37:30 - Lessons from Australia's MDMA Approval 39:00 - The Broader Psychedelic Landscape: Psilocybin, Ketamine, and Others 43:00 - Virtual Reality Exposure Therapy and the Brave Mind System 49:30 - Resilience, Hope, and the Future of PTSD Treatment LINKS Full transcript and show notes https://www.psychiatrist.com/jcp/ep16-forty-years-ptsd-frontier-barbara-o-rothbaum/ [https://www.psychiatrist.com/jcp/ep16-forty-years-ptsd-frontier-barbara-o-rothbaum/] Journal of Clinical Psychiatry https://www.psychiatrist.com/jcp/ [https://www.psychiatrist.com/jcp/] Dr. Barbara O. Rothbaum — LinkedIn https://www.linkedin.com/in/barbara-rothbaum-9339546 [https://www.linkedin.com/in/barbara-rothbaum-9339546] Emory Healthcare Veterans Program https://www.emoryhealthcare.org/lp/veterans-ptsd [https://www.emoryhealthcare.org/lp/veterans-ptsd] The intensive outpatient program for post-9/11 veterans discussed throughout this episode. Wounded Warrior Project — Warrior Care Network https://www.woundedwarriorproject.org/programs/warrior-care-network [https://www.woundedwarriorproject.org/programs/warrior-care-network] Funds the four IOP programs, including Emory's, discussed in the episode. No cost to veterans. #PTSD #TraumaTherapy #MDMAAssistedTherapy #VirtualRealityTherapy #Veterans

Rethinking Postpartum Depression: Biology, Biomarkers, and New Treatments with Jennifer L. Payne, MD

In this episode of the JCP Podcast, host Dr. Ben Everett speaks with Dr. Jennifer L. Payne, Professor of Psychiatry and Neurobehavioral Sciences and Vice Chair of Research at the University of Virginia, where she directs the Reproductive Psychiatry Research Program. Dr. Payne holds a joint appointment in obstetrics and gynecology and has spent her career at the intersection of basic neuroscience and clinical care in perinatal psychiatry. She is widely recognized for her work on the biological underpinnings of postpartum depression, including epigenetic biomarkers that prospectively predict risk, and for her clinical and research contributions to the development of GABAergic therapeutics — from brexanolone to zuranolone — that are reshaping how the field understands and treats this condition. Postpartum depression affects roughly one in eight women following childbirth and remains one of the most underdiagnosed and undertreated conditions in medicine. Despite this, care has long defaulted to serotonergic antidepressants developed for major depression rather than agents designed around the biology of the postpartum period. In this episode, Dr. Payne explains why the precipitous drop in neuroactive steroids — particularly allopregnanolone — following delivery may be central to postpartum depression pathophysiology, how the GABA-A receptor is implicated in ways that are distinct from benzodiazepines, what the clinical proof-of-concept established by brexanolone means for the field, and why zuranolone's oral formulation is changing real-world access. Dr. Payne also discusses the epigenetic biomarker test her lab has developed with collaborator Dr. Zachary Kaminsky — work now moving toward FDA review — its ethical implications, and emerging parallels with premenstrual dysphoric disorder. KEY EPISODE HIGHLIGHTS 🔬 PREDICTING POSTPARTUM DEPRESSION BEFORE IT STARTS [12:30] "We can take blood in the third trimester, and we can say whether a woman is at high risk of developing postpartum depression by three months postpartum or at low risk." Dr. Payne describes the epigenetic biomarker test developed with Dr. Zachary Kaminsky — replicated in six independent samples and now advancing toward FDA review — that identifies postpartum depression risk from a third-trimester blood draw, enabling preventive planning before symptoms emerge. 🧠 WHY BREXANOLONE IS NOT JUST A BENZODIAZEPINE [24:15] "The benzodiazepines don't act on those extrasynaptic GABA receptors. So sometimes people have said to me that allopregnanolone and the new FDA-approved treatments for postpartum depression are really just a benzodiazepine, and that's not true." Dr. Payne explains the critical mechanistic distinction between benzodiazepines (synaptic GABA-A binding) and neuroactive steroids (extrasynaptic GABA-A binding), clarifying why this difference matters for setting the brain's overall inhibitory tone — a distinction clinicians should be prepared to address with patients. 💊 ZURANOLONE: FOURTEEN DAYS, SUSTAINED RESPONSE [31:00] "You take [zuranolone] for fourteen days, and you see response rates within three days, which again, is groundbreaking in terms of treating a depressive episode." The shift from a 60-hour inpatient IV infusion to a 14-day oral course has transformed real-world feasibility. Dr. Payne reviews the clinical profile of zuranolone — including rapid onset, sedation considerations, breastfeeding questions, and the practical barriers that still limit access. CHAPTERS 00:00 - Introduction and Guest Overview 02:45 - Scientific Origins: From Alzheimer's Disease to Postpartum Depression 06:30 - Why Postpartum Depression Is a Natural Model for Studying Depression Biology 08:00 - Screening, Underdiagnosis, and the Stigma Gap 09:30 - A Personal Account of Postpartum Depression and Advocacy 12:00 - Epigenetic Biomarkers: Predicting Risk Before Delivery 17:15 - Ethics, Autonomy, and the Case for a Predictive Blood Test 20:45 - Allopregnanolone and the Neuroactive Steroid System 23:30 - GABA-A Receptor Subtypes: Why Neuroactive Steroids Are Not Benzodiazepines 25:30 - DoD-Funded Research: Neuroactive Steroid Shunting and GABA-A Reconfiguration 29:30 - Brexanolone: Clinical Proof of Concept and Why It's No Longer Available 31:30 - Zuranolone: Mechanism, Practical Considerations, and Real-World Access 37:00 - PMDD as a Window into Shared Biology 39:30 - The GABAergic Hypothesis and the Future of Depression Subtypes 41:45 - Improving Screening and Educating OBGYNs 43:30 - Closing Remarks LINKS Full transcript and show notes https://www.psychiatrist.com/jcp/ep15-rethinking-postpartum-depression-biology-biomarkers-jennifer-l-payne/ [https://www.psychiatrist.com/jcp/ep15-rethinking-postpartum-depression-biology-biomarkers-jennifer-l-payne/] Journal of Clinical Psychiatry https://www.psychiatrist.com/jcp/ [https://www.psychiatrist.com/jcp/] Publisher of peer-reviewed research discussed in this episode. National Pregnancy Registry for Antidepressants: https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/ [https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/] Biomarkers: * DNA methylation biomarkers prospectively predict both antenatal and postpartum depression: https://pubmed.ncbi.nlm.nih.gov/31843207/ [https://pubmed.ncbi.nlm.nih.gov/31843207/] * Seeing the Future: Epigenetic Biomarkers of Postpartum Depression: https://pmc.ncbi.nlm.nih.gov/articles/PMC3857665/ [https://pmc.ncbi.nlm.nih.gov/articles/PMC3857665/] * Biomarker or pathophysiology? The role of DNA methylation in postpartum depression: https://pubmed.ncbi.nlm.nih.gov/24059792/ [https://pubmed.ncbi.nlm.nih.gov/24059792/] DOD Work in Segment II: * Metabolites of Progesterone in Pregnancy: Associations with Perinatal Anxiety: https://pmc.ncbi.nlm.nih.gov/articles/PMC10530426/ [https://pmc.ncbi.nlm.nih.gov/articles/PMC10530426/] * Neuroactive steroid biosynthesis during pregnancy predicts future postpartum depression: a role for the 3α and/or 3β-HSD neurosteroidogenic enzymes? https://pubmed.ncbi.nlm.nih.gov/39885361/ [https://pubmed.ncbi.nlm.nih.gov/39885361/] #PostpartumDepression #NeuroactiveSteroidsGABA #PerinataMentalHealth #Zuranolone #EpigeneticBiomarkers

Catching Cognitive Decline Early with Gary W. Small, MD

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