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Introduction: Treatment Resistance in Psychiatry

Introduction: Treatment Resistance in Psychiatry


Treatment resistance is addressed in the latest edition of the Comprehensive Textbook of Psychiatry as follows: “Some patients fail to respond to repeated trials of medication. No single factor can explain the ineffectiveness of the various interventions in these cases. Strategies in these cases include the use of drug combinations, high-dose therapy, and use of unconventional drugs. Limited evidence is available on the comparative success rates associated with any given strategy.”1 This Special Report on treatment resistance provides expert guidance on how to treat patients who are still unresponsive after multiple unsuccessful attempts at intervention for some common mental disorders. ADHD, PTSD, panic disorder, and bipolar disorder are especially difficult to treat successfully, for a number of reasons.

In psychiatry, we are where ulcer treatment was a decade ago.

The quote above casts light on the dilemma psychiatrists face in everyday clinical practice. One is our lack of understanding of the underlying anatomical and biochemical abnormalities of any mental disorder, including the ones discussed in this report. You can even question whether treatment resistance is a valid concept when applied to psychiatric disorders. It’s reminiscent of a time not so long ago when peptic ulcer disease was considered resistant if the ulcers didn’t respond to the commonly used treatments—antacids, bland diets, and psychoanalysis (it was considered a psychosomatic disorder). The reason these interventions were largely ineffective is now understood: Helicobacter pylori caused most cases. Antibiotics are now the standard of care. In psychiatry, we are where ulcer treatment was a decade ago.

Currently, successful clinical outcomes are frequently the result of trial-and-error interventions, informed by limited and often anecdotal evidence. The fact is, none of the disorders covered in this report have a pharmacological treatment proven to be fully effective more often than not in most patients. One possibility is that there are multiple abnormalities in the CNS that account for the observed behavioral, emotional, and cognitive symptoms that we identify as a single disorder. The history of biological psychiatry has been marked with non-replicated claims that certain “markers” could predict treatment response.

There are also non-pharmacological causes of treatment resistance. These include noncompliance, medication intolerance, and inadequate dosage or duration of treatment. The most glaring cause of treatment failure in panic disorder that I observe is the use of benzodiazepines as needed when attacks occur. If the goal is to prevent the attacks, they should be taken on a regular schedule. In that way, the anticipatory anxiety and phobic avoidance can be slowly resolved. In ADHD, treatment often fails because the effects of even long-acting drugs tend to wear off by late afternoon. In the case of bipolar disorder, patients often discontinue their medication, deliberately or irresponsibly, and quickly lose insight into their emerging change of mood.

It is often said that psychopharmacology involves the art of using medications appropriately as well as the intrinsic effectiveness of the medications themselves. Hopefully, the information contained in this report will help clinicians improve treatment outcomes in some of the most challenging patients we encounter.


Dr. Sussman is an adult psychiatrist, NYU Langone Preston Robert Tisch Center for Men’s Health, New York, NY. Dr. Sussman reports no conflicts of interest concerning the subject matter of this Special Report.


1. Sadock BJ, Sadock VA, Ruiz P. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. 10th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2017. 

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