Real-world use of brexpiprazole during inpatient treatment for schizophrenia: continuation, discontinuation, and concomitant psychotropics

IntroductionIn the treatment of schizophrenia, antipsychotics used during acute inpatient care must control acute symptoms while remaining sufficiently tolerable to support treatment beyond the acute phase. Brexpiprazole, a serotonin-dopamine activity modulator may be one such option; however, its real-world use and short-term continuation in acute inpatient settings remain insufficiently characterized.MethodsWe conducted a retrospective observational study of inpatients with DSM-5 schizophrenia treated with brexpiprazole at a university hospital in Japan between June 2018 and July 2024. The index date (week 0) was defined as the date of brexpiprazole initiation during the index hospitalization. The primary outcome was brexpiprazole continuation at week 8. We compared baseline demographic and treatment-related variables between the continuation and discontinuation groups and summarized reasons for discontinuation from electronic medical records. As a secondary exploratory analysis, we examined longitudinal changes in Clinical Global Impressions–Severity scale (CGI-S) and Brief Psychiatric Rating Scale (BPRS) total scores (weeks 0/4/8) in the continuation group using a linear mixed-effects model including time, concomitant psychotropic medication status, and their interaction.ResultsSixty-seven patients were included. Baseline illness severity was substantial (median CGI-S 5.0 [IQR 5.0–6.0]; mean BPRS total 58.5 ± 9.6). Concomitant psychotropic medications were common. Thirty-six patients continued brexpiprazole to week 8 (53.7%). In unadjusted exploratory comparisons, continuation was associated with the female sex (p = 0.036), lower prior chlorpromazine-equivalent dose (p = 0.015), and shorter duration of untreated psychosis (p = 0.003), with a trend toward shorter duration since onset (p = 0.073). The most frequent reason for discontinuation was adverse events (n = 10, 32.3%), most commonly akathisia (n = 6), followed by insufficient efficacy (n = 9, 29.0%) and patient preference/refusal (n = 7, 22.6%). In exploratory mixed-effects analyses within the continuation group, CGI-S and BPRS total scores decreased over time, with significant group-by-time interactions by concomitant medication status. However, between-group differences should be interpreted cautiously.DiscussionThis study describes 8-week continuation and reasons for discontinuation of brexpiprazole in acute inpatient schizophrenia care. Given the retrospective single-center design and potential selection/information bias and unmeasured confounding, further studies are warranted to clarify its clinical positioning in real-world practice.

STAT+: Cytokinetics drug Myqorzo meets twin efficacy goals in study of genetic heart disease

Cytokinetics said Tuesday that its drug Myqorzo significantly improved heart failure symptoms and cardiovascular fitness in patients with non-obstructive hypertrophic cardiomyopathy, an inherited heart disorder. 

The results, reported in a company press release, achieved the dual efficacy goals of a Phase 3 clinical trial, called ACACIA, with statistical significance.

Cytokinetics is in the early days of Myqorzo’s commercial launch as a treatment for the more severe “obstructive” form of hypertrophic cardiomyopathy, or HCM. The successful outcome of the ACACIA study, if also cleared by regulators, could greatly expand the number of HCM patients eligible for treatment — and boost the drug’s peak sales to $5 billion annually, according to analyst forecasts. 

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A blueprint for using AI to strengthen democracy

Every few centuries, changes in how information moves reshape how societies govern themselves. The printing press spread vernacular literacy, helping give rise to the Reformation and, eventually, representative government. The telegraph made it possible to administer vast nations like the US, accelerating the growth of the modern bureaucratic state. Broadcast media created shared national audiences, which in turn fueled mass democracy.

We are now in the early stages of another such shift. Faster than many realize, AI is becoming the primary interface through which we form beliefs and participate in democratic self-governance. If left unchecked, this shift could further strain America’s already fragile institutions. But it could also help address long-standing problems, like lagging civic engagement and deepening polarization. What happens next depends on design choices that are already being made, whether we know it or not.

Start with what might be called the epistemic layer—how we come to know things. People are increasingly relying on AI to know what is true, what is happening, and whom to trust. Search is already substantially AI-mediated. The next generation of AI assistants will synthesize information, frame it, and present it with authority. For a growing number of people, asking an AI will become the default way to form views on a candidate, a policy, or a public figure. Whoever controls what these models say therefore has increasing influence over what people believe. 

Technology has always shaped the way citizens interact with information. But a new problem will soon arise in the form of personal AI agents, which can change not only how people receive information but how they act on it. These systems will conduct research, draft communications, highlight causes, and lobby on a user’s behalf. They will inform decisions such as how to vote on a ballot measure, which organizations are worth supporting, or how to respond to a government notice. They will, in a meaningful sense, begin to mediate the relationship between individuals and the institutions that govern them.

We’ve already seen with social media what happens when algorithms optimize for engagement over understanding. Platforms do not need to have an explicit political agenda to produce polarization and radicalization. An agent that knows your preferences and your anxieties—one shaped to keep you engaged—poses the same risks. And in this case the risks may be even more difficult to detect, because an agent presents itself as your advocate. It speaks for you, acts on your behalf, and may earn trust precisely through that intimacy.

Now zoom out to the collective. AI agents and humans could soon participate in the same forums, where it may be impossible to tell them apart. Even if every individual AI agent were well-designed and aligned with its user’s interests, the interactions of millions of agents could produce outcomes that no individual wanted or chose. For example, research shows that agents displaying no individual bias can still generate collective biases at scale. And setting aside what agents do to each other, there is what they do for their users. A public sphere in which everyone has a personalized agent attuned to their existing views is not, in aggregate, a public sphere at all. It is a collection of private worlds, each internally coherent but collectively inhospitable to the kind of shared deliberation that democracy requires.

Taken together, these three transformations—in how we know, how we act, and how we engage in collective governance—amount to a fundamental change in the texture of citizenship. In the near future, people will form their political views through AI filters, exercise their civic agency through AI agents, and participate in institutions and public discussions that are themselves shaped by the interactions of millions of such agents.

Today’s democracy is not ready for this. Our institutions were designed for a world in which power was exercised visibly, information traveled slowly enough to be contested, and reality felt more shared, if imperfectly. All of this was already fraying long before generative AI arrived. And yet this need not be a story of decline. Avoiding that outcome requires us to design for something better.

On the informational layer, AI companies must ramp up existing efforts to ensure that models’ outputs are truthful. They should also explore some promising early findings that AI models can help reduce polarization. A recent field evaluation of AI-generated fact checks on X found that people with a variety of political viewpoints deemed AI-written notes more helpful than human-written ones. The paper is yet to be peer-reviewed, but that is a potentially revolutionary finding: AI-assisted fact-checking may be able to achieve the kind of cross-partisan credibility that has eluded most manual human efforts. Greater understanding of and transparency about how models make these assertions and prioritize sources in the process could help build further public trust.

On the agentic layer, we need ways to evaluate whether AI agents faithfully represent their users. An agent must never have an agenda of its own or misrepresent its user’s views—a technically daunting requirement in domains where users may have not explicitly stated any preferences. But faithful representation also cannot become an accessory to motivated reasoning. An agent that refuses to present uncomfortable information, that shields its user from ever questioning prior beliefs or fails to adjust to a change of heart, is not acting in the person’s best interest.

Finally, on the institutional level, policymakers should hurry to harness AI’s potential to make governance more responsive and legitimate. Several states and localities are already using AI-mediated platforms to conduct democratic deliberation at scale, building on research showing that AI mediators can help citizens find common ground. As agents become increasingly common participants in public input processes—and there is already evidence that bots are skewing those processes—identity verification for both humans and their agentic proxies must be built in from the start.

What is needed is a new generation of democratic infrastructure, technological and institutional, built for the world that is actually here. Failing to design for democratic outcomes, in a domain this consequential, means designing for something else. And the history of unaccountable power does not leave much room for optimism about what that something else tends to be.

Andrew Sorota and Josh Hendler lead work on AI and democracy at the Office of Eric Schmidt.

Opinion: The ‘brain drain’ narrative about health professionals misses half of the story

About 10 years after a breast surgeon we interviewed returned to Dubai to practice, a colleague stopped her in a hospital corridor to tell her: “It’s great — since you came back I no longer see those advanced cases of breast cancer.”

She had not stopped to notice. “You get on the wheel,” she told us in an interview for our research. When you return to your home country after training abroad, you run your clinics, train your nurses, drive out to women’s groups in the hinterlands to give talks, design educational videos that explain breast self-examination without showing a breast, because that is what the censors will pass. You argue to have the word “breast” printed on your medical license; the authorities prefer “chest.” You establish a support group, then a drop-in center, likely the only cancer drop-in center in the Middle East. Somewhere in the middle of all that, you alter what late-stage breast cancer looks like in your country.

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Neural Correlates of Suicidal Behavior in Youth

Conditions: Suicidal Ideation; Suicide Attempt; Suicidal Behavior; Depression / Major Depressive Disorder; Hopelessness; Neurobiological

Interventions: Behavioral: CAMS

Sponsors: The Cleveland Clinic; MQ Mental Health Research

Not yet recruiting

The PREVENT Resilience Study

Conditions: Psychological Trauma

Interventions: Device: Transcranial Magnetic Stimulation (TMS); Other: TMS Sham

Sponsors: Emory University; National Institute of Mental Health (NIMH)

Not yet recruiting