4 Signs Your Schizophrenia May Be Treatment Resistant

This podcast episode by Dr. Tracey Marks delves into the critical topic of treatment-resistant schizophrenia, defining it as the inadequate resolution of symptoms after taking at least two non-Clozapine antipsychotic medications at therapeutic doses for a sufficient duration. The episode highlights that approximately 30% of individuals with schizophrenia experience persistent psychotic symptoms despite medication. It identifies four key predictors for treatment resistance based on a 2019 study: an early age of onset (before age 20), being male, being born in autumn or winter, and poor premorbid functioning, which includes difficulties in school due to disorganized thoughts and prominent negative symptoms like social withdrawal or impoverished speech.

The discussion meticulously distinguishes between medication failure and medication intolerance, emphasizing that a medication stopped due to side effects (intolerance) does not count as a treatment failure. A crucial distinction is also made between negative symptoms, which represent an absence of normal functions (e.g., blank stare, impoverished speech), and positive symptoms, which add something not typically present (e.g., hallucinations, delusions). The podcast notes that negative symptoms are not exclusive to schizophrenia and can be observed in conditions like social anxiety and autism spectrum disorder, underscoring the complexity of psychiatric symptomology.

The episode then focuses on the management of treatment-resistant schizophrenia, positioning Clozapine as the most potent antipsychotic available, unparalleled in its ability to alleviate severe symptoms, including profound disorganized thoughts and 'word salad' (schizophasia). However, Dr. Marks thoroughly explains why Clozapine is not a first-line treatment, detailing its significant side effects such as massive weight gain and, more critically, neutropenia (a dangerously low neutrophil count). The rigorous monitoring protocol for Clozapine, involving frequent blood tests and registration in a monitoring system, is outlined, emphasizing the high maintenance required to manage its risks.

For individuals who cannot tolerate Clozapine or choose not to use it, the podcast explores alternative treatments. Electroconvulsive therapy (ECT) is presented as a long-standing option with the best track record for improving schizophrenia symptoms. Repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS) are mentioned as newer, more experimental, and in the case of DBS, invasive treatments that require further research to establish their effectiveness. The episode concludes by reinforcing the challenges and complexities involved in treating severe, persistent mental illness, highlighting the ongoing need for effective and tolerable therapeutic options.

About 30% of people with schizophrenia continue to have psychotic symptoms even on medication.

Treat resistant is when you don't have an adequate resolution of your symptoms after taking at least two antipsychotic medications that are not Clozapine.

The most robust predictor is an early age of onset.

Poor premorbid functioning... Some examples of poor functioning would be doing poorly in school, usually because of the disorganized thoughts... Another example... is having prominent negative symptoms.

They're called negative symptoms because they're an absence of something.

Clozapine is the strongest medicine that we have to treat schizophrenia. No other medicine has come close to the power that it wields in knocking out symptoms.

The serious side effect of Clozapine is a low neutrophil count called neutropenia.

I've seen a few people who were practically non-functional because of severe disorganized thoughts just clear up with Clozapine. It was amazing.

Word salad is speech that's so disorganized, you can't make any sense of it. Another term for it is schizophasia.

ECT has been around the longest and has the best track record for improving schizophrenia symptoms.