The 'game-changing' treatment for schizophrenia
US poised to approve KarXT as new antipsychotic treatment for disorder, which could offer reduced side-effects
The US Food and Drug Administration (FDA) is poised to regulate a "potential first-in-class antipsychotic", known as KarXT, said Medscape.
About one in 300 people worldwide are affected by schizophrenia, but for decades treatment options have been both static and limited. If the FDA approves the twice-daily pill on Thursday, as it is "widely expected" to do, it will be "the first truly novel treatment" for schizophrenia in more than 70 years, said the Financial Times. The decision on the experimental treatment could "pave the way for its rollout in global markets".
What is schizophrenia?
Schizophrenia is a "long-term mental health condition" which causes a wide range of symptoms, according to the NHS. Often described as "a type of psychosis", its effects mean the patient may not be able to "distinguish their own thoughts and ideas from reality". Symptoms usually emerge in adolescence and can include hallucinations, delusions and social isolation.
Subscribe to The Week
Escape your echo chamber. Get the facts behind the news, plus analysis from multiple perspectives.
Sign up for The Week's Free Newsletters
From our morning news briefing to a weekly Good News Newsletter, get the best of The Week delivered directly to your inbox.
From our morning news briefing to a weekly Good News Newsletter, get the best of The Week delivered directly to your inbox.
The disorder is thought to result from "genetic predisposition", and can be exacerbated by environmental factors such as stress or drug use, said the FT. The worst flare-ups can cause "psychotic breakdowns that last for weeks".
Schizophrenia does not generally cause people to be violent, but sufferers are highly stigmatised and "frequently pushed to the fringes of society". They are also "vastly overrepresented" in the unemployed, homeless and prison populations in the US. Steve Paul, a neuroscientist who developed the precursor to KarXT, has called the disease the "cancer of psychiatry" because of the sheer damage it does to sufferers, including potentially reducing their life expectancy by almost 30 years compared to the average.
What are the treatment options?
Schizophrenia is usually treated with a combination of cognitive behavioural therapy, community support and antipsychotic medication. The development of antipsychotics in the 1950s was a "milestone" in schizophrenia management, said The Lancet. The hypothesis was that schizophrenia was caused by hyperactive dopamine, so medications that blocked dopamine such as chlorpromazine and, later, clozapine, were "groundbreaking".
But these treatments come with "extensive side-effects", from listlessness to movement disorders and heart disease. That contributes to "underprescribing" by doctors, as well as reluctance of patients to keep taking them. Non-adherence rates are incredibly high: about 75% of patients are thought to discontinue treatment. About a third of people with schizophrenia are resistant to conventional antipsychotic treatment.
The current "pharmaceutical arsenal is limited". Clinical trials for new medications are expensive and, in the case of psychiatric drugs, are difficult to assess due to "strong placebo effects". The result? A "steady loss of enthusiasm and investment" in new treatments.
How does KarXT differ?
KarXT essentially combines an experimental drug for Alzheimer's (xanomeline) with another drug (trospium) which suppresses side-effects associated with antipsychotics.
Developed by Karuna Therapeutics, now part of Bristol Myers Squibb (BMS), it works by targeting receptors in the brain that modulate dopamine release, rather than blocking it directly.
Results of its latest trial, published in January, showed that it significantly reduced acute psychotic symptoms. "You get the high levels of efficacy that you anticipated with the [antipsychotics], however, you don't get the consequence that comes with it," Carlos Dortrait, SVP and general manager of US immunology and neuroscience at BMS, told BioSpace.
"I'm very optimistic and hopeful that [KarXT] will be a breakthrough medication," said Jeffrey Conn, scientific co-founder of Karuna Therapeutics and now professor emeritus of pharmacology at Vanderbilt University, Tennessee.
Are there any downsides?
KarXT "does not have a spotless profile", said BioSpace. There are potential cardiovascular risks, including hypertension, and the long-term efficacy is still unclear. Trials so far have been short-term, and participants were predominantly African American males. Pricing is also a challenge: KarXT could cost up to $20,000 a year, which may limit access.
Factors such as poverty, housing and social stigma also play a significant role in outcomes for people with schizophrenia.
"How much can new therapeutics solve this crisis when you have an underfunded mental health system with an inadequate workforce and a chaotic melange of services?" said Ken Duckworth, chief medical officer of the non-profit organisation National Alliance on Mental Illness. "It's a piece of the puzzle but it's not a panacea."
Sign up for Today's Best Articles in your inbox
A free daily email with the biggest news stories of the day – and the best features from TheWeek.com
Harriet Marsden is a writer for The Week, mostly covering UK and global news and politics. Before joining the site, she was a freelance journalist for seven years, specialising in social affairs, gender equality and culture. She worked for The Guardian, The Times and The Independent, and regularly contributed articles to The Sunday Times, The Telegraph, The New Statesman, Tortoise Media and Metro, as well as appearing on BBC Radio London, Times Radio and “Woman’s Hour”. She has a master’s in international journalism from City University, London, and was awarded the "journalist-at-large" fellowship by the Local Trust charity in 2021.
-
'Underneath the noise, however, there’s an existential crisis'
Instant Opinion Opinion, comment and editorials of the day
By Justin Klawans, The Week US Published
-
2024: the year of distrust in science
In the Spotlight Science and politics do not seem to mix
By Devika Rao, The Week US Published
-
The Nutcracker: English National Ballet's reboot restores 'festive sparkle'
The Week Recommends Long-overdue revamp of Tchaikovsky's ballet is 'fun, cohesive and astoundingly pretty'
By Irenie Forshaw, The Week UK Published
-
The future of fluoridated water is up for debate
The Explainer The oral benefits are watery
By Devika Rao, The Week US Published
-
The hidden cost of lead exposure on American mental health
Under The Radar Millions of mental health diagnoses have been linked to childhood lead exposure in new study
By Theara Coleman, The Week US Published
-
Will the murder of a health insurance CEO cause an industry reckoning?
Today's Big Question UnitedHealthcare CEO Brian Thompson was shot and killed in what police believe was a targeted attack
By Justin Klawans, The Week US Published
-
Bird flu one mutuation from human threat, study finds
Speed Read A Scripps Research Institute study found one genetic tweak of the virus could enable its spread among people
By Peter Weber, The Week US Published
-
Polycystic ovary syndrome: what it is, how it's treated and why it's often misunderstood
The Explainer PCOS affects millions, but there is still no cure outside of treating symptoms separately
By Theara Coleman, The Week US Published
-
The growing list of conditions weight-loss drugs could help with
The Explainer Ozempic and similar drugs have been linked to possibly helping diseases beyond diabetes and obesity. Are they miracle drugs?
By Theara Coleman, The Week US Published
-
Dark chocolate tied to lower diabetes risk
Speed Read The findings were based on the diets of about 192,000 US adults over 34 years
By Peter Weber, The Week US Published
-
The great departure: Texas OB-GYNs are leaving the Lone Star State
Under the radar The state is suffering an exodus of health care professionals, creating more maternity care deserts
By Theara Coleman, The Week US Published