Overcoming Challenges in Schizophrenia Treatment

In Part 2 of this video, Heather Flint, senior digital managing editor, Psych Congress Network, sits down with Psych Congress Steering Committee Member Craig Chepke, MD, FAPA, Medical Director, Excel Psychiatric Associates, Huntersville, NC, to continue a discussion on schizophrenia. Dr Chepke discusses challenges in treating patients with schizophrenia, and shares insights on potential treatments.

In the previous Part 1, Dr Chepke discussed psychiatric comorbidities in schizophrenia, adverse events in medication, and the potential for future treatments.

Read the Transcript:

Heather Flint:  What do you feel are the biggest challenges in treating patients with schizophrenia? Outside of TAAR1, are there other emerging treatments that may help combat these challenges?

Dr Chepke:  Many challenges, obviously. One big one is that the treatments that we have in terms of antipsychotics, they can do fairly well for most patients. Only about 30% of patients are resistant to the treatment with antipsychotics, but that's in terms of the positive symptoms.

The 70% of patients might get a good response from positive symptoms from current antipsychotics, but none of the current antipsychotics do reach out from negative symptoms. The cognitive symptoms as well.

Those two clusters of symptoms are equally as important, if not, more important than the positive symptoms, schizophrenia. Such a huge challenge that only one out of the three symptom clusters is being well-addressed at all in any percentage of patients with schizophrenia.

The negative and cognitive symptoms are often more debilitating in the long term and cause more quality of life difficulties for the person and for the family, and the community than the positive symptoms do. Positive symptoms are what get you hospitalized, but negative symptoms and cognitive symptoms often cause the long-term disability is the way that I'll put it.

That's a huge challenge. The comorbidities, not being able to address those well, and non-adherence. That often is unintentional. I can't blame people if they have debilitating side effects from a medication that only partially addresses their symptoms. It's not a great talking proposition for them to take it every day of their life.

It's challenging to treat from a number of mentions. That's why it's great to look to the horizon of maybe we can get something better. Other than TAAR1, there are a couple of other mechanisms. I'll say the most promising one other than TAAR1 is muscarinic agonism.

Anticholinergic medications we've used for many years for different purposes. It's known to be a very anticognitive in nature can lead to an increased prevalence of dementia in people who are in anticholinergics. However, cholinergic agonists could be potential source of hope.

However, they have a lot of adverse reactions peripherally that make it uncomfortable and hard for patients to tolerate. There is one company that has paired a muscarinic agonist with a peripheral muscarinic antagonist. It doesn't cross blood-brain barrier.

You don't get the cognitive adverse reactions and some of the other adverse reactions. Peripherally, the rest of the body, the procholinergic and anticholinergic cancel out on average. The peripheral side effects are much reduced.

That's promising because in the brain you get the cholinergic agonism and that has shown preclinically and some early clinical trials of Phase 2. They are starting a Phase 3 program. It does show antipsychotic effect. Also, potentially, some procognitive effects as well.

That is another promising avenue that could bear some fruit in the next few years.

Heather Flint:  Are there any other final thoughts or information that you want to share with our network building off of your session talking about TAAR1, schizophrenia?

Dr Chepke:  I'm going to turn and look straight to the audience. The main thing I want to share with you is that do not give up on your patients with schizophrenia. Do not lower your expectations. If we as clinicians lower our expectations of what our patients can achieve and what their chance of recovery are, then how are they ever going to believe in themselves?

We need to keep fighting for our patients for schizophrenia, raise our expectations, and try to get them the best quality of life that we can and just not give up, and trying to achieve recovery for them.

Heather Flint:  Thank you so much, Dr. Chepke. We are very excited that you chose to join us today.

Dr Chepke:  My pleasure, Heather. Thanks.