In this episode, I break down one of the most interesting new developments in schizophrenia treatment: a medication that treats psychosis without dopamine blockade. And it also works for negative symptoms.

I’m talking about xanomeline–trospium, brand name Cobenfy, a muscarinic-based therapy that targets M1 and M4 receptors, avoids extrapyramidal symptoms and metabolic side effects, and is not technically classified as an antipsychotic by the FDA. I walk through the mechanism, the EMERGENT trial data, efficacy for both positive and negative symptoms, side effect profile, dosing pearls, and where this might fit clinically.

We spend a lot of time explaining psychiatric medications in terms of neurotransmitters and receptors, but that may be the wrong level of abstraction. In this episode, I argue that psychiatric illness is better understood as a problem of brain circuits and information processing, not low-level mechanisms like receptors, and that this helps explain why treatments like ECT and clozapine work when others don’t. We should instead investigate how medications affect actual brain functioning at a circuit-level, and to do that we will have to think beyond neurotransmitters.

There’s a new FDA-approved treatment for depression that you can do entirely at home called the FL-100 device by Flow Neuroscience.

In this episode, I talk about transcranial direct current stimulation, or tDCS, a low-level brain stimulation technique that’s been around for years but just received FDA approval based on a large clinical trial. I break down how it works, what the data actually show, how it compares to antidepressants, and why the results are both promising and a little confusing.

What exactly is the mental status exam, and why does it matter so much in psychiatry?

In this episode, I walk through the mental status examination point-by-point. I cover what each section is really trying to capture, how much variation there is between clinicians, and how a well-written MSE should let you imagine what it was like to sit in the room with the patient.

We talk through appearance, behavior, speech, mood and affect, thought process and content, perception, cognition, judgment, and insight, with concrete examples.

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In this episode, I talk about some genuinely exciting developments in transcranial magnetic stimulation, including new accelerated and even one-day TMS protocols that may outperform traditional antidepressant treatments, both in efficacy and cost. Conventional TMS usually takes nine weeks of daily treatment but new advances are making a full course of treatment possible in a single day, with surprisingly high remission rates.

I walk through how TMS works, why standard protocols have been so hard to scale, and what newer approaches like SAINT and one-day protocols using medication priming might mean for the future of mental health care. If these results hold up, they could dramatically change how we treat depression, anxiety, and possibly much more.

Can a panic attack trigger a full psychotic episode that resolves within hours?

In this episode, we discuss apparently rare and fascinating clinical presentations where panic attacks appear to precipitate brief psychotic symptoms, including hallucinations, paranoia, and disorganized behavior, followed by rapid and complete recovery. We discuss the differential diagnosis for this presentation and how that might guide management.

Insomnia is one of the most common clinical problems in psychiatry, both as a symptom of primary psychiatric disorders like mood and anxiety disorders, and as a primary sleep disorder. In this episode I share my thoughts on how to manage insomnia in clinical practice and make some points about how we often give up too quickly on trazodone and how we can increase the adenosine in our brains.

Note: I mistakenly said the pineal gland naturally produces “nanograms” of melatonin, but it is actually in the microgram range. Nonetheless, as alluded to in the episode, exogenous melatonin supplements can be 10-100x higher than natural melatonin amounts.

How do you clinch the diagnosis efficiently? In this audio essay I review some of the main clinical reasoning styles that physicians of all specialties must use when presented with a new clinical case. Namely, we discuss inductive reasoning, deductive reasoning, and pattern-matching. Being able to identify which reasoning process you’re using in a case could save you from diagnostic errors. In a follow-up episode I will give some longer-form concrete examples.

In this episode I introduce a condensed version of David Burn’s (author of the famous books Feeling Good and Feeling Great that popularize CBT) version of CBT that he calls TEAM CBT, where TEAM is an acronym that stands for Testing, Empathy, Assessment of resistance, and Methods. I use this approach with appropriate patients on the inpatient unit with good success and I have developed a worksheet for clinicians to use to structure the therapy session, which typically takes 15-20 minutes. You can find the worksheet here: https://drive.google.com/drive/folders/1MQ0m6vgM0aNJVVwxnAPOv2wytQstaRZX?usp=sharing

In this episode I give a broad overview of aripiprazole including details from the official prescribing information as well as weaving in my own clinical experience and opinions. I talk about my experience using aripiprazole off-label as monotherapy for severe depressive episodes.