KELLIE NEWSOME: Today, we look at a controversial study that threatens to change the course of gender-affirming care. Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003.

CHRIS AIKEN: I’m Chris Aiken, the editor in chief of the Carlat Report.

KELLIE NEWSOME: And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue. We'll start with a preview of the CME quiz for this episode.

A. Aripiprazole

B. Dextromethorphan

C. Guanfacine

D. Topiramate

Dr. Johanna Olson-Kennedy is the president of the US branch of WPATH, the medical society that has set the standard for gender affirming care since the 1970’s. Until recently, she led one of the largest centers for gender-affirming care at the Children's Hospital of Los Angeles. In 2025, the hospital closed her clinic amid mounting political pressure. The federal government had announced it would cut funding from hospitals providing medical treatment for transgender youth. Earlier, the Supreme Court upheld a Tennessee law prohibiting some gender transition treatments. Her clinic was not alone. Stanford, Kaiser Permanente, and NYU have closed their clinics since the White House changed hands in 2025. But few clinicians have been targeted as specifically as Dr. Olson-Kennedy. The reason, as reported two years ago in the New York Times, is a controversial study that has been weaponized against gender-affirming care. 

CHRIS AIKEN: In 2015, Dr. Olson-Kennedy took charge of a large, 10-million-dollar NIH-funded study of hormonal therapy for gender dysphoria. She and her colleagues administered puberty-blocking hormones to 95 children — average age 11 — and tracked their mental health during the treatment. To her surprise, their mental health didn't change. To the rest of the field's surprise, she didn't publish the results. Instead, she continued re-analyzing the data, searching for an angle that would place the treatment in a better light. She argued that mental health hadn't changed because the patients were doing well to begin with — but a report of the baseline data contradicted that: half had depression, and more than half had anxiety. Then she said something that gave her critics what they were looking for. She told the media she hadn't published the data because she didn't want the negative findings to "fuel the kind of political attacks that have led to bans of the youth gender treatments in more than 20 states." Dr. Olson-Kennedy did publish the outcomes last year. The journal posted them as a preprint, still awaiting peer review. And when that peer review comes, they might take issue with some of the conclusions. The paper argues that puberty suppression probably prevented mental health from worsening, even if it didn't improve it, but the data doesn’t address prevention. The summary claims they saw stability and improvement, but the improvement is hard to find in the numbers. At the start of the study, 18% of patients had poor mental health. By the end, that figure had risen to 22%. A separate study from Dr. Olson-Kennedy's group raises similar concerns. This one involved hormone therapy after puberty in 315 children aged 12 to 20. Over two years, their mental health improved — but the results, published in 2023 in the New England Journal of Medicine, were not particularly striking, showing much greater improvement in satisfaction with appearance than in other mental health outcomes. The mental health gains were small enough that we'd expect comparable benefits from care and attention alone — the placebo effect. There were more problems. Outcomes that the authors said they would measure were mysteriously left out of the publication. Among the missing were metabolic and physiological measures. That matters because other studies have documented delays in bone growth and fertility loss with hormonal therapy. Also left out were measures of substance use, risky sexual behavior, and self-injury. During the study, two of the 315 patients died by suicide, a rate 50 times higher than that of a comparable gender clinic in London, where most patients were not taking hormones. This may be a statistical flux, but it wasn’t even addressed by the authors, and the rate is striking given that patients with significant psychiatric problems were excluded from enrollment.

KELLIE NEWSOME: Letters to the editor rolled in decrying the New England Journal for publishing a trial with no randomization and no control group, but Dr. Olson-Kennedy walked away with different take. She published a paper arguing that randomized trials are not needed in gender-affirming care because the observational data is already so positive. Still, all these arguments over statistical significance and prespecified outcomes can get lost in the public sphere. What her political critics have focused on is not the statistics — it's the delay. A $10 million NIH-funded study sat unpublished for years, and Republicans have launched a formal investigation.

RFK JR:  “On my watch, HHS will stand for radical transparency and informed consent.”

CHRIS AIKEN: But if transparency is the issue, we have to apply equal scrutiny to the other side. In 2025, the Department of Health and Human Services — led by Robert F. Kennedy Jr. — released a report on Treatment for Pediatric Gender Dysphoria. They claimed it was unbiased, but withheld the names of the authors, only releasing them 6 months later under pressure from critics, praising their courage in stepping out. 

JAY BHATTACHARYA: “The extraordinary courage of the authors of the HHS report, uh, I, I don't know if you're all here in the, in the room today, is, is, is, is, is stunning to me because they, they put their-- they stuck their heads up.”

CHRIS AIKEN: That was NIH Director Jay Bhattacharya.  When the names came out, we learned that the authors had limited experience with this population and known biases against gender-affirming care. Later, a judge overruled the administration’s attempts to defund gender affirming care by claiming it was unsafe and ineffective. The problem? They made those claims without going through the required scientific review. The Make America Healthy Again movement was supposed to be about transparency, but the administration has threatened medical journals with censorship. And closer to home, they've tried to censor this podcast. I was invited to speak at a program sponsored by the Department of Health and Human Services, and was told that if I criticized the administration publicly before the conference, my talk would be cancelled.

KELLIE NEWSOME: Dr. Olson-Kennedy may be the focal point of the gender debate, but another development now threatens her work more directly. On December 5, 2024, one of her former patients filed a malpractice lawsuit against her and the team that oversaw her surgery. The patient — we'll call her A.B. — is a 20-year-old drama student who started puberty blockers with Dr. Olson-Kennedy in 2016, at age 12. She progressed to testosterone at 13 and underwent a double mastectomy at 14. How she arrived at gender-transitioning care at 12 is not fully clear, but by her own account, it began with therapy for depression. During those sessions, she mentioned she might be trans — but, in her words, "I also mentioned that I might be a lesbian and that I might be bisexual — I wasn't really sure about my identity at all." Looking back now as a young adult, she believes her problems were rooted in trauma. She went through abuse at age six, and later witnessed violence in her home from her brother, who has severe autism. She claims her counselors ignored those problems and focused on the possibility that she was transgender. They called her parents, and with their support, A.B. changed her name and pronouns. Three months later, she began treatment with Dr. Olson-Kennedy.

CHRIS AIKEN: As with the New York case, glitches in the medical record that might look innocent in and EMR cast a more ominous shadow in the harsh lights of the courtroom. Dr. Olson-Kennedy diagnosed A.B. with gender dysphoria — but only documented three months of symptoms. The DSM requires six. Later, she told the surgeon the dysphoria had been present since early childhood, though her own clinical notes contradicted that. To obtain parental consent for hormone therapy, Dr. Olson-Kennedy reportedly told the family that A.B. was suicidal. But there is no documentation of suicidality in the record. Her notes at the time describe A.B. as in no distress, according to the Economist, who reviewed the medical record. 

KELLIE NEWSOME: I gotta say something more on that. How many times have you used a default normal mental status exam in an EMR, populating the chart with phrases like “Judgment intact,” – which later comes back to haunt you when the patient’s disability gets denied – or “No acute distress,” which – in this case – doesn’t fit with the jury’s image of a suicidal patient.

CHRIS AIKEN: If anything, A.B.’s record suggests worsening mental health as testosterone therapy progressed. By 2020, A.B. [quote] "compulsive[ly] cutting to see if he has blood." A psychiatrist at the clinic diagnosed A.B. with tics, psychosis, obsessions, and compulsions. A.B. attributes the worsening to testosterone. Dr. Olson-Kennedy has since published an uncontrolled study showing testosterone does not worsen aggression in transgender youth, but hormones are notorious for causing changes in opposite directions. Excess thyroid can cause anxiety, or lower it, and oral contraceptives can stabilize mood or worsen it.

KELLIE NEWSOME: A.B. is now living as a woman. She credits dialectical behavior therapy with stabilizing her mental health.

CHRIS AIKEN: Dr. Olson-Kennedy's study is not the first to raise questions about whether gender transition improves mental health. Next week, we'll look at a similar study from the 1970’s that brought down the first gender surgery clinic in the US at Johns Hopkins. Next, a research update on clozapine resistant schizophrenia, but first let’s hear from Lindsey Spero, who transitioned from female to male through hormones and surgery:

LINDSEY SPERO: “Right now, despite the fact that I live in a state that wants to legislate me out of existence, I'm happy and loved, and I have community. I have people around me who care about me. For the first time in my life, I feel safe to explore myself in ways that I never could before because I didn't trust myself, and I didn't trust my body. I have been given that gift through testosterone. I've been given the gift of, like, re-seeing myself for the first time ever.”

KELLIE NEWSOME: When patients don't respond to clozapine, there's close to no research to guide us — which makes this study by Naveen Hegde and colleagues in the Asian Journal of Psychiatry is a big step forward: Augmentation of clozapine with dextromethorphan in treatment-resistant schizophrenia: A randomized, group sequential adaptive design, controlled clinical trial. Extremethorphan is familiar as the antidepressant accelerator in Auvelity, but the rationale to use it here comes from a glutamatergic theory of schizophrenia. The study, conducted in India, randomized 40 adults with treatment-resistant schizophrenia who hadn’t recovered on clozapine to dextromethorphan 30 mg daily or placebo for 12 weeks. They didn’t use any inhibitors like quinidine to extend dextromethorphan’s half-life.

CHRIS AIKEN: Dextromethorphan outperformed placebo on both positive and negative symptoms, with a large effect, a number needed to treat of 2. That’s impressive, but we’ll take it with a grain of salt given the sample size. The trial was small on purpose. They stopped it early after an interim analysis showed that the benefits were large enough to show a clear difference with a small sample. At 30 mg, dextromethorphan didn't worsen psychosis, despite its potential to cause dissociation and hallucinations at higher doses. One astute reader asked whether adding a cough suppressant to clozapine — which carries a pneumonia risk — could compound that respiratory danger. Probably not. Studies suggest no increased pneumonia risk with cough suppressants.

KELLIE NEWSOME: The bottom line: dextromethorphan is worth considering for clozapine resistance, but with one trial, it's not ready for routine use. Search all of Dr. Aiken's research updates by topic at chrisaikenmd.com — click LEARN, then RESEARCH UPDATES. He adds one to two updates every day. You can also follow Dr. Aiken's research updates on social media. Search ChrisAikenMD on LinkedIn, Twitter, Facebook, Bluesky, and we’re back on Threads. The Carlat Report is one of the few CME publications that depends entirely on subscribers. Thank you for helping us stay free of commercial support.