By Moryt Milo
After more than 70 years of antipsychotic medications that are mere iterations of earlier discoveries, a door may have cracked open to offer better options for individuals struggling with severe mental illness.
There is much more research to be done, said Dr. Jacob Ballon, who specializes in the treatment of individuals with psychotic disorders including schizophrenia and is Co-Director of the INSPIRE Clinic at Stanford. But he is excited about new medications coming down the pipeline that take a different approach to treating psychosis. Medications that could reduce side effects such as weight gain, metabolic symptoms, drowsiness, and involuntary movements.
Dr. Ballon describes himself as a holistic thinker, looking beyond each mechanism within the brain. He prefers to step back and look at the entire system through a broader lens.
“We lose sight of what is the big picture and start to view psychiatry as raising one receptor and decreasing another to get the answer,” he said. “That approach to psychopharmacology has never resonated with me, never really worked for me. It’s not how I think, except to say categorically there are mechanisms that are different than dopamine drugs.”
Today, all the medications on the market work through the dopamine D2 receptor. That’s about it, he said. Everything else is a variant of that.
It doesn’t mean the generics don’t have a role or that everyone should be on newer medications, especially if the person is doing well. But long-term there needs to be better medications without the current array of serious side effects such as weight gain and drowsiness. There are no medications on the market that don’t come with a risk of weight gain, Ballon said.
Some medications like Olanzapine, brand name Zyprexa, can cause excessive weight gain by as much as 100 pounds. This in turn causes health consequences later on. Extreme drowsiness—a person sleeping 12 to 14 hours per day—poses another problem. The person is unable to work, go to school, or have any kind of a social life.
“If you can’t do anything the medicine is helping you to do, then when that happens it’s a real problem,” he said.
It’s important to note that psychosis is a very generic thing, Ballon said, and yet, on an individual level we don’t know what is going on. New medications use different mechanisms that aren’t focusing on dopamine receptors. They could be the next generation of antipsychotics.
Ballon explains these new drugs simply. Let’s say a person has a severe headache and takes a Tylenol but the headache doesn’t go away. Then the person adds some ibuprofen. Each medication works differently but similar enough to be synergistic and the headache subsides.
This may be how a new crop of drugs works. It doesn’t focus on dopamine receptors but on different mechanisms like one called muscarinic agonism. This drug has antipsychotic properties that reduce psychosis. This novel approach does not cause weigh gain which leads to metabolic symptoms. The new drug, developed by Karuna Therapeutics under the name KarXT, is slated to receive FDA approval by year’s end. The drug has been in development for more than a decade and was recently acquired by pharmaceutical giant Bristol Myers Squibb for $14 billion.
Stanford will start trials soon after it comes to market. The trial will look at KarXT as an adjunct medicine with an antipsychotic. Those qualifying for the trial will be individuals whose symptoms are stable but not where they would like them to be.
Another drug called Emracladine, also a part of the muscarinic receptor group, was recently acquired by AbbVie, demonstrating the pharmaceutical sector is starting to put more time and money into novel approaches to treating schizophrenia.
Stanford has other trials, one pertains to tardive dyskinesia, a disorder that causes involuntary movements caused by antipsychotics. There is a class of drugs, vesicular monoamine transporter 2 (VMAT2) inhibitors, used for this disorder. The drug might also reduce the risk of psychosis and Stanford is pre-screening for candidates to participate in the trial.
“At the end of the day, the [dopamine] D2 receptors is giving the most bang for the buck,” Ballon said. But neuropsychiatry needs to take treatment to the next level. Ballon hopes some of these newer drugs working in tandem with what already exists can make that happen.
To watch Dr. Ballon’s NAMI presentation, click here. Learn more about Stanford’s INSPIRE Clinic and its clinical trials.
