The 'game-changing' treatment for schizophrenia

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.

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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."