A Breakthrough in Schizophrenia Treatment

Schizophrenia is a debilitating mental illness that affects people across all regions, cultures, and socioeconomic backgrounds. With an estimated 24 million cases globally, according to the World Health Organization, the disorder places a significant burden not only on individuals and their families but also on healthcare systems worldwide. 

Despite its prevalence—affecting more people than Parkinson’s disease or multiple sclerosis—treatment options have remained largely unchanged for decades. Further, too many patients face a cycle of relapse due to medication side effects and poor adherence.

For international health correspondents, schizophrenia represents a pressing global issue. The condition disproportionately affects vulnerable populations, contributes to homelessness, and often intersects with public health challenges such as inadequate access to psychiatric care, social stigma, and economic instability. In lower-income countries, where mental health services are often scarce, patients can go untreated for years, if not a lifetime.

 Now, for the first time in 70 years, a new treatment offers hope for more effective and accessible schizophrenia care. This breakthrough could reshape mental health treatment not just in high-income countries but also in regions where psychiatric resources are limited.

Existing treatments for schizophrenia, which are mostly unchanged since the 1950s, focus on dopamine receptors, and while these help reduce psychotic symptoms, they too often cause severe side effects. These include Parkinson’s-like movement disorders, weight gain, and increased vulnerability to diabetes and heart disease. 

The good news: For the first time in 70 years, there’s a new approach to treating schizophrenia. The drug Cobenfy uses the traditional dopamine-targeting approach but also employs two compounds that in combination improve symptom control while reducing side effects.

Dr. Sam Clark, neuroscientist and CEO of Terran Biosciences, says that Cobenfy uses xanomeline (a compound developed in the 1990s, that improved schizophrenia symptoms. However, the nausea and diarrhea that accompanied it were severe enough to cause the developers to abandon it) and trospium chloride (a compound that blocks receptors in the gut but does not cross into the brain; In other words, it didn’t cause nausea or diarrhea, and it didn’t affect the brain). In combination, the two compounds are able to prevent the stomach issues while taking advantage of xanomeline’s ability to improve schizophrenia symptoms. However, a drawback is that the current version requires twice-daily dosing. This tends to make it harder for patients to follow their regimen. 

In response, researchers at Terran Biosciences are working on a once-daily formulation and also a long-acting injectable. A promising avenue for reducing the frequency of doses is using prodrugs. A prodrug is a medication that is inactive or less active when taken but converts into an active drug inside the body.

The advantage of a prodrug is it can be designed to release the active drug slowly, reducing the need for frequent dosing. This is especially useful for conditions requiring long-term medication adherence, as in the case of schizophrenia.

Developing a new medication typically takes over a decade, requiring extensive trials and safety studies. However, in the United States,  the 505(b)(2) regulatory pathway speeds up the approval process for prodrugs by allowing companies to use existing safety data. Instead of starting from scratch, researchers can conduct fewer studies, reducing approval time to about five years.

 At Terran Biosciences, Dr. Clark has pioneered a rapid drug development program that uses small, expert teams focused on solving specific problems efficiently. Depending on which obstacle they’re trying to overcome in bringing a medication to market, a team might have three to possibly ten world experts that work to find a solution to the particular problem. The teams work six days a week, and the days the different teams work are staggered so that in effect, research work is going on seven days a week.

“We’ve conducted over 2,500 experiments and analyzed 1,500 prodrugs to identify the best candidates for human trials,” says Clark. Their work resulted in a 4,000-page patent submission, one of the largest ever filed, reflecting their extensive research.

 The research into preventing serious side effects and having once a day or long term injectables is critical because too patients with schizophrenia struggle to take their medication consistently. This leads to relapse and worsening symptoms.

Non-adherence is a major factor contributing to homelessness—studies estimate that more than 20% of the global homeless population suffers from psychotic illness, with schizophrenia making up the majority of cases.

“Early and consistent treatment is critical,” Clark emphasizes. “Schizophrenia causes structural brain changes, and untreated psychosis can accelerate cognitive decline. Patients who receive treatment early and stick to their medication tend to have better long-term outcomes.”

For patients, families, and healthcare providers, these innovations represent a transformative shift in schizophrenia treatment. With better drug options, more people could maintain stability, avoid relapses, and live healthier, more independent lives. The world may witness that what was once an untreatable and debilitating disorder may soon become a manageable condition, ushering in globally, a new era of improved mental health care.