Treatment resistance is a myth!

But what about the 50% of patients with TRS or refractory schizophrenia who do not respond to clozapine?⁹ They do not have TRS, either, but represent different schizophrenia biotypes that may respond to other medications with different mechanisms of action, such as lamotrigine,¹⁰ which is a glutamate modulator; pimavanserin,¹¹ which is an inverse agonist of the serotonin 5HT-2A receptor; allopurinol,^12,13 an adenosine modulator; or estrogen,¹⁴ a neurosteroid. Future research will continue to unravel the many biotypes of the highly heterogeneous schizophrenia syndrome that are “nondopaminergic” and do not respond to the standard class of dopamine antagonists (previously called neuroleptics and now known as antipsychotics).¹⁵ Future treatments for schizophrenia may depart from modulating various neurotransmitter receptors to targeting entirely different neurobiologic processes, such as correcting mitochondria pathology, inhibiting microglia activation, repairing white matter, reversing apoptosis pathways, inducing neuroplasticity, arresting oxidative stress and inflammation, and other neuroprotective mechanisms.

The rapid growth of biomarkers in psychiatry¹⁶ will usher in an era of precision psychiatry¹⁷ that will eliminate the term “treatment resistance.” Our psychiatric practice will then benefit from “canceling” this demoralizing and clinically unjustified term that has needlessly fostered therapeutic nihilism among psychiatric physicians.