KELLIE AIKEN: We follow Lindsay Clancy from hypomania to depression to the border of psychosis, and learn that dissociation doesn’t always point to past trauma.

CHRIS AIKEN: Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor-in-chief of the Carlat Report.

KELLIE AIKEN: And I’m Kellie Aiken, a psychiatric NP and a dedicated reader of every issue. Today, we’ll learn more hidden signs of mania and psychosis as Lindsay Clancy’s illness spirals downward. We’ll end with a newly identified, and potentially fatal, side effect of GLP-1 receptor agonists. But first, a preview of the CME quiz. Find the full test through the link in the show notes.

1. Which recreational substance has the strongest link to thiamine deficiency?

A. Alcohol

B. Nicotine

C. Opioids

D. Methamphetamine

When we left Lindsay Clancy last week, she was four months postpartum. It was autumn in Massachusetts, and the hypomania of her summer was crashing into depression. Unmotivated, unable to sleep, and desperate with anxiety, she sought treatment and started sertraline. When the dose was raised to 50 mg, she did not sleep for 48 hours. Her thoughts raced, her anxiety grew, and she felt “awful.”

CHRIS AIKEN: In the DSM, mania is defined by a decreased need for sleep, but the DSM is not using the word “need” the way it’s used in common speech. They mean that the patient keeps going; they don’t catch up by sleeping all day, even if they feel they need to. But ask a manic patient whether they need sleep, and they’re liable to say they’re desperate for sleep. It’s often their chief complaint. They sense that more sleep would calm their agitation, or they want something strong to knock them out and shut off the racing thoughts that crowd their mind. Even when patients truly don’t need sleep, we can miss the diagnosis. I saw a woman who slept between zero and three hours a night after starting venlafaxine, but her psychiatrist still diagnosed unipolar depression. Why? She convinced her doctor that the lack of sleep was intentional. “I had read that geniuses like Thomas Edison didn’t need much sleep, and I too am a kind of genius, so I decided to stop sleeping in order to fulfill destiny.” So she stayed up, night after night, writing the great American novel.

KELLIE AIKEN: Kraepelin saw this too. He wrote of manic patients who convinced others of their sanity through their gifts of locution, persuasion, and a charismatic force of will. That’s why DSM criteria work better when we stick to observable signs. Patients are quick to explain the meaning, intent, or cause of their symptoms. “Of course I didn’t sleep, my eBay sales were flying through the roof, I had so much to do.” Stick to basics. Ask: “Do you ever sleep less than usual but still keep going, even if you wished you could get more sleep?”

CHRIS AIKEN: Lindsay’s lack of sleep was a sign of mania, as was the triggering event: an antidepressant. When a patient stops sleeping on an antidepressant, ask about manic symptoms. At the very least, pull out a screening instrument like the Mood Disorder Questionnaire or the Hypomanic Check List-32 and have the family complete one. Better yet, bring the family in. Lindsay’s clinicians skipped those steps. They stopped sertraline and started lorazepam and diphenhydramine, Benadryl. They treated the insomnia as a symptom, when it was a clue to the diagnosis.

KELLIE AIKEN: For the rest of this podcast, I’m going to read directly from the malpractice lawsuit that Lindsay Clancy’s attorneys filed in January of 2026. It’s a legal document and only tells one side of the story, and we can’t vouch for their claims. We’re looking at what this story means for our patients – and what it tells us about the experience of bipolar. Here we go. On November 16, 2022, Lindsay's insomnia had become so severe that she took herself to the emergency room at South Shore Hospital seeking help. She reported insomnia, anxiety, and palpitations. The ER doctor prescribed trazodone for sleep, but it was not effective.  Lindsay reported to the nurse practitioner that she was "very frustrated and scared," experiencing "extreme insomnia" averaging only three hours per night, and having racing thoughts. The NP prescribed fluoxetine on November 21, 2022.

NP AUDIO CLIP:  “But, uh, or why, why Prozac? Why start there? “ “Because she'd had a history of being successful on it in the past, and that's a good indicator that, instead of trialing multiple medications, to start with the ones that actually work. So when Prozac can sometimes be very activating, it can make the anxiety worse before it gets better when you first start it. So I wanted to pair it with the Ativan just in the beginning, just to help her be more comfortable with the anxiety and to make sure that it didn't interfere with her sleep.”

KELLIE AIKEN: After merely four days on fluoxetine, Lindsay reported that the medication intensified her insomnia. She immediately informed her providers, and the fluoxetine was discontinued.

CHRIS AIKEN: When people with bipolar disorder get worse on an antidepressant, it’s usually on one of the first few they try. We see that here: two days without sleep on sertraline, followed by worse insomnia on fluoxetine. I don’t have any studies to cite on this one; it’s my own experience. Maybe the brain is more reactive to these medications early in the course of bipolar disorder, like dry wood ready to catch fire. Later, the flame fails to catch. The antidepressants fall like duds, like a match tossed onto a pile of ash.

KELLIE AIKEN: Four days after stopping fluoxetine, the NP prescribed three different medications: zolpidem, mirtazapine, and clonazepam. On November 26, 2022, after taking mirtazapine, Lindsay experienced dissociation—perceiving the world around her as unreal, distorted, and distant. She was unable to determine what was real. She became disoriented, forgetful, confused, and disconnected from her own body, disoriented and forgetful. She was unable to drive and unable to be alone. She was still sleeping only three hours per night.

CHRIS AIKEN: Dissociation, derealization, and disorientation are common in mania and psychosis. The DSM leaves them out of the criteria because they’re non-specific, or as we say, transdiagnostic - they turn up in many disorders – panic, PTSD, schizophrenia, bipolar, borderline. Some think they are a sign of past trauma, and sometimes that’s true; but generally they are just a marker for greater severity. In Lindsay’s case, with 20/20 hindsight, I suspect they represented a transitional state, as she shifted from depression with mixed features into psychotic depression. These delirium-like features are even more common in postpartum psychosis.

DR. BHAT: There are some features which might be specific to postpartum psychosis. The thing that is described as a classic presentation is a delirium-like picture, so waxing and waning symptoms, depersonalization, and derealization, disorientation that waxes and wanes. Because of this waxing and waning nature, it is very possible that they might present to you perfectly normal and oriented and not endorsing any psychotic symptoms. But like 15 minutes later, they might be endorsing psychotic symptoms might appear disoriented.

CHRIS AIKEN: That was Dr. Amritha Bhat, a perinatal psychiatrist at the University of Washington in Seattle. We interviewed her last February in the Carlat Report, and her description answers a question that came up often during the Clancy trial. Can someone shift quickly from normal to full psychotic and back again? Making snowmen one minute and murdering children the next? Yes, and this kind of fluctuation is particularly common postpartum. In a new study of postpartum psychosis, nearly half the women said their symptoms waxed and waned. Even when psychosis is stirring in the mind, these patients can appear normal, or at least rational, to others. Dr. B-, who specializes in postpartum disorders, said they could pass for normal at a cocktail party. That’s a stark contrast with schizophrenia, where distorted thinking and social oddities pervade the presentation. But when psychosis occurs as part of a mood disorder, or postpartum, patients usually maintain a sense of social propriety. They know we won’t agree with their delusions, and often fear we’ll take their children away. So they explain away the paranoia, minimize it, hide it away; and we miss it. In one study, clinicians missed 30% of cases of psychotic depression, and that was at academic inpatient centers. But that study had good news for young doctors: the residents detected psychosis better than their attendings did.

KELLIE AIKEN: For Kraepelin, this drive to rationalize their behavior was a core feature of mania. With extraordinary acuteness the patient can find a reason for all his astonishing and nonsensical doings; he is never at a loss for an excuse or explanation. In the hospital, the patient usually presses for discharge from the first day… declaring offhand that the physicians are "crazy." And, as Kraepelin goes on to tell it, there were always people ready to believe them, including one of his colleagues, “a physician who had obtained a certain reputation for certifying mentally unsound people as sane.”

CHRIS AIKEN: But we’re getting ahead of ourselves. Lindsay hasn’t yet expressed full psychosis, but that is about to come. We’ll start there next week.

KELLIE AIKEN: Today’s research update covers a rare but serious risk with GLP-1 agonists: Wernicke’s encephalopathy. It’s a systematic review of case reports on semaglutide, Ozempic, from the journal Obesity.

CHRIS AIKEN: The problem here is thiamine deficiency; vitamin B1, something we associate with alcoholism, and a reason I recommend B vitamins for every patient with alcohol use disorder. It’s not going to stop their drinking, but it’s a harm reduction approach, and a potentially life-saving one. But alcohol is not the only cause of thiamine deficiency. Poor nutrition and malabsorption can also cause it, and that’s the pathway we worry about with GLP-1 agonists. They lower appetite and slows gastric emptying, causing nausea, vomiting, and poor nutritional intake. If that goes on long enough, it can cause thiamine depletion. The result is Wernicke’s encephalopathy: acute brain damage that presents with confusion, abnormal eye movements, and an unsteady gait. Left untreated, it can progress to the permanent amnesia of Korsakoff syndrome.

KELLIE AIKEN: The authors found six case reports of Wernicke’s on semaglutide. Most were women in their 40s who’d taken semaglutide for about five months before symptoms began. Five of the six had other chronic illnesses, like diabetes, thyroid disease, or psychiatric disorders. All of them had GI side effects and substantial weight loss before the neurological signs appeared. The outcomes were poor. One patient died, four were left with permanent memory impairment. Only one recovered fully. Six cases can’t tell us how often this happens. Case reports lean toward dramatic outcomes, so they may overstate the severity. But they might also understate frequency, since most cases of Wernicke’s go undiagnosed, even at autopsy. The mechanism here makes sense – we see the same problem after bariatric surgery or with hyperemesis.

CHRIS AIKEN: The risk probably extends beyond semaglutide. Tirzepatide and liraglutide have case reports of thiamine deficiency too, which points to a class effect.

KELLIE AIKEN: The bottom line: When you see a patient on a GLP-1, ask about nausea, vomiting, reduced intake, and rapid weight loss. If those are showing up, recommend oral thiamine 100 mg a day, just as you should do for a patient with alcoholism. In the rare case of an emergency – sudden gait disturbance or confusion – send them to the hospital for intravenous thiamine.

CHRIS AIKEN: Join us next week for the final episode in our Clancy series.

KELLIE AIKEN: To write the new Complementary and Alternative Medicine in Psychiatry Fact Book, Dr. Aiken applied the criteria used by the FDA and the Cochrane group to rank 67 therapies by the evidence, covering nearly 2,000 placebo-controlled trials. You'll find off-label answers for depression, bipolar, schizophrenia, autism, anorexia, antidotes for side effects, and natural alternatives to benzodiazepines.