#Schizophrenia Drug

[xtruss]

Food and Drug Administration (FDA) Approves the First New Schizophrenia Drug in Decades

— By Alice Park | September 27, 2024

Steve Belkowitz (Bristol Myers Squibb)

No new treatments for schizophrenia have been approved in nearly three decades, but that changed on September 26, when the U.S. Food and Drug Administration (FDA) approved Cobenfy for the psychiatric disorder.

Developed by Karuna Therapeutics, which was subsequently acquired by Bristol Myers Squibb, the drug works in an entirely different way from existing medications for schizophrenia, which is building excitement and enthusiasm among doctors and patients alike.

How Scientists Developed The New Drug

While schizophrenia treatments primarily target the dopamine neurotransmitter system in the brain, Cobenfy goes after a different one, the cholinergic system, through muscarinic receptors. Decades ago, scientists at Eli Lilly had studied the muscarinic system as a possible treatment for Alzheimer’s disease, since manipulating it seemed to reduce some of the symptoms of Alzheimer’s-related psychosis that some patients develop. The company's researchers also serendipitously learned that a compound they developed to activate the system also improved symptoms of schizophrenia. But cells in many parts of the body—the brain, but also the bladder, gut, salivary glands, eyes, and heart—contain receptors for the muscarinic system, which meant it was challenging to selectively target just those in the brain and not elsewhere. Because the compound, called xanomeline, caused wide-ranging side effects, Lilly's researchers shelved further study on it.

Andrew Miller, co-founder of Karuna, became intrigued by this research and tried to figure out how to activate the muscarinic system in the brain while tamping it down elsewhere in the body. He and his team tested 7,000 compounds and eventually combined xanomeline with a drug that had been approved by the FDA in the 1970s for treating overactive bladder, to suppress muscarinic activity elsewhere in the body. "It's a pretty out-of-the-box approach," says Miller. The overactive bladder drug "has nothing to do with psychiatry," he said. Combining it with a serendipitous discovery of xanomeline "didn't fit the traditional model of innovative drug discovery." But it worked.

What Studies Have Found

In a study the company published last December in the journal Lancet, the researchers reported that the combination—now called Cobenfy but then called KarXT—helped to significantly reduce symptoms of schizophrenia such as hallucinations, delusions, paranoia, social withdrawal, and a loss of motivation compared to a placebo. Those data were part of the application that the company submitted to the FDA for approval.

Bristol Myers Squibb acquired Karuna in 2023 largely based on these encouraging results. “When we looked at the available neuroscience and neuropsychiatric assets out there, we didn’t want the next dopamine agonist or antagonist in the marketplace, which all of the physicians have [already] seen,” says Adam Lenkowsky, chief commercialization officer for Bristol Myers Squibb. “We wanted a truly revolutionary asset, one with a different mechanism: a first-in-class, best-in-category asset we think could transform the space.”

Samit Hirawat, chief medical officer at Bristol Myers Squibb, says that not only does Cobenfy address schizophrenia in an entirely new way, but its approach could be used for other neurological conditions as well. "The breadth of applicability of this medicine is what attracted us.”

Dr. Rishi Kakar, chief scientific officer at Segal Trials who led several studies on Cobenfy, says that “the uniqueness of the mechanism of action differentiated this medication from everything else we had so far, and truly caught my eye right off the bat.” Kakar—a psychiatrist who treats patients as well as conducts research—says that historically, only about 40% of people with schizophrenia respond to dopamine-based treatments, and the other 60% who may respond often stop taking their medications because of intolerable side effects, which can include uncontrolled muscle movements, dizziness, fainting, and weight gain.

The trials included patients who were hospitalized for acute schizophrenia and randomly assigned to receive Cobenfy—as a pill taken twice a day—or a placebo for five weeks. In order to reflect the real-world population of patients, some had been taking existing medications but stopped because of the side effects, or weren’t compliant. All patients went through a wash-out period of up to two weeks to ensure any measurements of their outcomes during the study were due solely to Cobenfy or placebo. Patients received escalating doses of the drug, and prescribing doctors were able to adjust dosages for their patients depending on their symptoms.

The studies documented a significant reduction in overall symptoms of schizophrenia in the patients receiving Cobenfy compared to placebo. “My viewpoint is that [this difference] can mean someone can potentially carry on a better life by having symptom control,” says Kakar.

What Else To Know About Cobenfy

The FDA approved Cobenfy as a monotherapy—meaning it is meant to be taken alone, without other medications—but more studies will be needed to see how the medication works in combination with existing treatments, and what the benefits and risks are of combining them. “I think many clinicians are going to try this as a first-time pharmacological option, because they will find that the reduction in symptoms is fairly robust,” says Kakar. “From what I saw, it has true value for the unmet need we have.” Lenkowsky says Bristol Myers Squibb is conducting a trial studying Cobenfy in combination with dopamine-based medications that will yield results in about a year.

In contrast to the existing dopamine-based treatments, the side effects of Cobenfy reported by the volunteers in the studies were mostly mild to moderate, involving nausea and gastrointestinal distress, and tended to lessen with time. The label also alerts patients that the drug is associated with urinary retention, increased heart rate and swelling in the face in rare cases; the medication is not recommended for people with a history of liver or kidney disorders.

Bristol Myers Squibb is continuing to study the drug for its longer term effects, as well as to understand and potentially guide doctors on how to adjust doses for patients as their symptoms change over time. The success in schizophrenia patients may lead to other uses of the drug in other conditions as well. “Neuropsychiatry is at the cusp of bringing an explosion of new medicines, and Cobenfy is the start of a pipeline of potential products,” says Hirawat. The company is currently studying the drug in Alzheimer’s-related psychosis, and next year plans to start late-stage trials investigating whether it can improve bipolar mania, Alzheimer’s-associated agitation, and Alzheimer’s-associated cognitive impairment. In 2027, the company hopes to begin trials in people with autism.

How Much Will Cobenfy Cost?

According to a Bristol Myers Squibb spokesperson, the wholesale cost for a month's supply will be $1,850. Depending on people's insurance coverage, that cost could be lower for individual patients. Bristol Myers Squibb estimates that 80% of people with schizophrenia in the U.S. have insurance coverage either through Medicare or Medicaid.

[schizopositivity]

If you see any videos online of a mentally ill person in public being filmed without their consent, please report it as harassment. Examples include: a video of someone talking to someone who isn't actually there, a video of someone having strange or erratic behaviors, a video of someone speaking gibberish or talking incoherently, etc.

This is a huge violation of the person in the videos privacy and extremely disrespectful. They could be having the worst day of their life. They could be homeless with no support system or access to care, with nowhere else to be but in public. They might not see that you are filming, and have no idea or control over who sees them in a vulnerable state. Please consider the feelings and safety of the people in these videos, they are already going through enough as it is, you don't need to add to their problems by filming, posting, or even just watching these videos.

No one is better than the mentally ill people in these videos. Everyone is capable of having a mental health crisis that leads to strange behavior in public. How would you feel if someone posted your worst moments online for people to laugh at? These are human beings that deserve the same amount of respect as anyone else in the world. Yes, even if they are homeless, or on drugs, or swearing, or dirty, or disturbing the peace of a public area. That is a human being no matter what.

As someone with schizophrenia, it's so disgusting how often I come across videos like that online (yes, even on Tumblr). A lot of these "strange" behaviors that are being filmed are literally just symptoms of mental illnesses like schizophrenia. The person cannot control what they are doing, and might not be aware that it is perceived as strange. It's also important to acknowledge that people with severe and persistent mental illnesses are at an increased risk of violence by others, homelessness, substance use disorders, being arrested, and being involuntarily committed into psychiatric facilities. Alienating us and reinforcing stigma against us can contribute to those risks. It's also worth noting that paranoia is a symptom of schizophrenia, and knowing that people are willing to film us in public to ridicule us at our vulnerable moments is extremely paranoia inducing. This can cause us to fear going out in public, which leads to isolation, which makes the symptoms of schizophrenia worse.

There is so much risk associated with the filming, posting and viewing of these videos. Plus it further dehumanizes a disenfranchised minority. Is it really worth it? Is the few seconds of "entertainment" really worth all this distress you are causing?

If you want to advocate for mentally ill people, or even just care at all, you must stop this from happening. Don't film people in public without their consent. Don't post videos of people in public without their consent. Don't like, share or comment on videos of people in public filmed without their consent, it just boosts it in the algorithm. Report any instances of this that you see, even if you think "this one's not that bad" or "the person doesn't seem distressed in this one" or "okay but this one is actually funny", no excuses, report it.

[girlwdresams]

[seizurestrong]

List of people that deserve better

Palestinians, trans lesbians, older gay men, fat people, bears, schizophrenics, people with cluster b disorders, children, people who are still scene/emo, people who get tummy aches often, disabled individuals, autistics, enbys, addicts, he/him lesbians, migraine havers, trans guys that aren’t on T, people that don’t drive, people who struggle to take care of themselves, those with anger issues, people who have made mistakes, you

[cartoonscientist]

this fake text is obviously a hipaa violation but I can’t believe how mean people were being about schizophrenic people in the comments?? my reaction was just “aw that’s nice that the therapist could recognize it as a roomba and ask them to turn it off, that’s considerate”

but also I guess in case I need to fully explain things: if this were real, which it’s not, its not like the patient is just straight up hearing roomba noises and attributing them to ghosts. schizophrenia can distort and mess with sensory input. so if you were to tell them “that’s just a vacuum cleaner, you can relax, you’re being weird”, that would be like someone telling you that the screams of the damned which are very audibly coming from your neighbor’s apartment are actually just a vacuum cleaner and you need to relax. and if you do believe them? cool. doesn’t change the fact that your neighbor is running a vacuum cleaner that sounds like mass murder while you’re trying to focus.

imagine the worst psychedelic trip you’ve heard about or experienced and just assume that a schizophrenic person is experiencing that if they piss you off by being “stupid”.

[harmonyisharpingonme]

Addiction is hard, but I can do this. There's so many reasons to be sober and so many joys in life that I can cherish without the use of drugs. I've been through so much, and for most of what I've been through, I was sober.

I got this. I can do this. I just have to make it through today, and when tomorrow rolls around, I have to make it through tomorrow. This attempt feels different. I feel like I finally want to change and grow. I feel like I finally have the tools I need to accomplish my sobriety goals.

I got this.

[dorianbrightmusic]

New Antipsychotic FDA Approval – Cobenfy

Cobenfy (xanomeline/trospium chloride) has just been approved for schizophrenia treatment in the US. This is huge. It's the first antipsychotic in decades to not target dopamine directly. It's got a much, much better side-effect profile, and it might work for negative and cognitive symptoms.

FOR MORE READING – news report/patient-centred plain language overview: See here.

FOR MORE READING – scientific evidence report: See here (note: the drug is referred to as 'KarXT' in this report).

I couldn't be happier right now. People with psychosis go through so, so much trying to find medications that are both useful and tolerable, and psychiatry has historically neglected psychotic people's needs so, so awfully. (Not to mention how little there is that actually helps with anything other than positive symptoms.) So I'm really, really hoping that with the proof that we can, in fact, make antipsychotics that aren't based on the same old pharmacological things we've tried before. Cobenfy is a muscarinic agonist/antagonist in fixed combination – and it also indirectly regulates dopamine and glutamate. And given that we know both dopamine and NMDA are probably involved in schizophrenia somehow – AND that treating things to do with either is hard – this is so, so, so exciting.

This isn't to say Cobenfy doesn't have side-effects (the most common ones being nausea, constipation, dyspepsia, vomiting, hypertension, dry mouth, and tachycardia. We also know that there is a small risk of extrapyramidal symptoms, and that prolactin-related side-effects do happen, unfortunately). We don't know much about how it affects folks in the long-term, or much about the long-term tardive dyskinesia risk. But even so, it's progress compared to some of the worse antipsychotic side-effects.

Moreover, there is a possibility it might be useful for negative and cognitive symptoms. Holy crap.

I'm really really really excited. I hope this is the start of a shift in psychiatry towards better standards of patient-centred care for psychosis. Y'all have deserved better for far too long – here's hoping this is the start of more ethical, effective treatment.

[neuroticboyfriend]

hey med taking and drug doing folks. don't take multiple CNS depressants at once, or combine them with other drugs that affect your vital signs. it can kill you - and will, if you don't pay attention to what you're taking and how it's affecting your body.

for example. I used to take seroquel XR, topiramate, and prazosin all at once. every night. while having sleep apnea and dysautonomia. i was used to sedation because i'd been on seroquel for years - but with that combo, it genuinely felt like my heart was gonna stop every time i took my meds, and i was too sedated to do anything about it once it started.

i did not realize that is. absolutely not a normal side effect and could kill me (because of trauma from gaslighting). so yeah. don't do it, trust your body, and always check for drug interactions - no matter where you got the meds/drugs from, you may not have been given accurate information. nothing is more important than your life.

[schizodelicpunk]

Vince/V

He/him

19

INFP

Psychotic and just generally crazy

I am not a good person, I'm a fucked up crazy street kid and I don't really care anymore.

content warnings

psychosis talked about in a glorifying light/as a gift

drugs

Yknow what, fuck it consolidating all blogs, you will see horny shit here too, block #nsft and #minors dni if you're bothered

Art in header is mine

[ineedsertralina]

rgL in the other Morld

[schizopositivity]

Why it's hard for schizophrenic people to get treatment and diagnosis for physical health problems:

• Having "schizophrenic" in our charts makes a lot of medical professionals automatically not believe us. Especially if it is a problem that they can't instantly see themselves. They may think we are either delusional or having some kind of tactile hallucinations. They could see it more as a "psychiatric problem" rather than the physical medical problem that it is.

• If you have flat or blunted affect, they may not believe you, especially if you are describing pain. They have the expectations that you would be screaming, crying, grimacing, etc. When you are straight faced and monotone and say "I am in extreme pain right now" they will likely not believe you. And this paired with medical professionals views of chronic pain just makes them not believe you even more.

• Alexithymia makes describing your symptoms very hard, and even harder to describe how the symptoms affect you. The medical professional goes off of what you tell them, if you are vague or don't have the words, they will not understand you or not believe what you are describing. Either way that will hinder your road to treatment and diagnosis.

• Having memory problems, or trouble keeping track of things can also hinder your care. If you can't remember, or even remember to write down how often a symptom occurs, how long it lasts, how it felt in the moment, and how it impacted your life at the time, they may once again not believe you. Diagnosis often requires some sort of timeline or prevalence of symptoms, and not keeping track of that could keep you from diagnosis.

• They may avoid prescribing pain killers (even if you need it) because the fact that schizophrenic people are more likely to abuse drugs than the general population. And while that fact is true, it doesn't mean that someone in extreme pain does not deserve the right to pain killers just as much as anyone else who needs them.

• Being part of a disenfranchised group while also being schizophrenic can have compounding affects on your physical health treatment. Being low-income, being a person of color, being assigned female at birth, being transgender, being intersex, any other disenfranchised group or any combination of these will impact how you are treated by the healthcare system.

• Fear of medical professionals, or fear of Dr.s offices can impact the quality of your visit. You may feel too frightened to tell them how you really feel, you may just completely avoid going into the building at all. This can happen to anyone but is especially common for schizophrenic people due to our paranoia, inability to advocate for ourselves, lack of self esteem, historical medical abuse or personal experiences with medical abuse. Plus we can have doubts about the quality of our care because of any of the other reasons listed above.

And all this occurs while we as schizophrenic people, are at higher risks of several physical health problems (you can read about it here):

[romanticfistfightz]

@smashstiel ceiling demon trap + torchwood boxset bc i love it so much its also from vinted <3 ^_^

also this is what my neighbours see cuz i spend time with my red light on all yhe time

[schizofreaknia]

can you tell how the mood episode is going?

[hole34]

when you’re sober and start remember shit and it freaks you out so bad like why do i have this much consciousness oh my god what the fuck is happening to me

[sathin]

List of my favorite movies about mental illness (or just worth watching)

Girl interrupted (1999) borderline personality disorder

To the bone (2017) anorexia

28 days (2000) alcohol, drugs, mental hospital

A beautiful mind (2001) schizophrenia

The basketball diaries (1995) drugs

Vertigo (1958) psychological thriller

Thirteen (2003) self harm

Skins (2007(7seasons)) teens problems

Insatiable (2018(2seasons)) binge eating

Trinkets (2019(2seasons)) stealing

Split (2016) many personalities

Bojack horseman (2014(6seasons)) alcohol, drugs, sex, depression

I’ll be updating soon

[vent-art-af]

Me and my best friend made these for each other since we’re both lithium girlie(guy)s and thought some of you might appreciate this 💊🫶