The Current State of the Art and the Not Too Distant Future

Psychiatric TimesVol 39, Issue 1

Put treatment resistance in perspective with Sheldon H. Preskorn, MD.




The authors of the 3 articles in this Special Report have done a commendable job. Not only will you, the reader, benefit from reading these discussions, but, ultimately, so will your patients.

A few comments may help to put the issue of treatment resistance in perspective:

1. In these articles, the term treatment resistance is describing the illness the patient has rather than the patient being resistant. The importance of this distinction cannot be overstated. Caveat: There are patients who may decline treatment, but that is a different topic for a different time.

2. Patients do not fail treatments. Instead, treatments fail patients. This distinction also cannot be overstated.1

3. Pharmacotherapy and psychotherapy are complimentary rather than antagonistic modalities. When explaining the relationship, I use the analogies of computer science in terms of hardware and software in computer science and/or orthopedic procedures (eg, casts) and physical therapy to explain the interrelationship between pharmacotherapy and psychotherapy.2 Psychotherapy, like physical therapy, may be the only treatment the patient needs; however, it is rarely the case that a patient only needs pharmacotherapy without some form of psychotherapy, even if it is limited to supportive, educational psychotherapy.

4. There are 4 levels to diagnostic sophistication arranged like a pyramid.3 The first level is symptomatic diagnosis, which is what patients say when they present to a health care provider (HCP) (eg, “I have a headache.”). Moving up in the pyramid, the second level is syndromic, which is a cluster of symptoms and/or signs (ie, physical findings), and the HCP may say to the patient : “You have a migraine headache.”). The third level up is pathophysiology, which is based on laboratory findings, such as elevated levels of norepinephrine in the bloodstream that causes the headache. The fourth level and top of the pyramid is pathoetiology, which is the cause of the patient problem. In our example, a tumor, a pheochromocytoma, could be causing the high levels of norepinephrine which increased the patient blood pressure resulting in the headache.

As one can see, the higher the level of the diagnosis, the greater the understanding of the problem, what is causing the problem, and how to most effectively treat it. The lowest 2 levels of our pyramid are descriptive diagnoses, whereas the higher 2 levels are explanatory.

Presently, most psychiatric diagnoses are syndromic but we are moving to higher levels of understanding. That is good news for patients with treatment resistant psychiatric illnesses.4

Dr Preskorn is professor in the Department of Psychiatry and Behavioral Sciences at the Kansas University School of Medicine-Wichita. Over his 42-year academic medical career he has worked with more than 140 pharmaceutical, biotechnology, device, and diagnostics companies to bring their products to the market. He has been a principal investigator at the site level on all antipsychotic and antidepressants medications approved in the United States over a 25-year period of time. He has received grants/research support from or has served as a consultant, on the advisory board, or on the speaker’s bureau for Alkermes, BioXcel, Eisai, Janssen, Lyndard, Otsuka, Sunovion, and Usona Institute. All clinical trial and study contracts were with and payments made to The University of Kansas Medical Center Research Institute, a research institute affiliated with The University of Kansas School of Medicine-Wichita.


1. Preskorn SH. Patients don’t fail treatments, treatments fail patients. J Prac Psych and Behav Hlth. 1997;3(3):165-168.

2. Preskorn SH, Baker B. The overlap of DSM-IV syndromes: potential implications for the practice of polypsychopharmacology, psychiatric drug development and the human genome project. J Psychiatr Pract. 2002;8(3):170-177.

3. Preskorn SH. Psychopharmacology and psychotherapy: what’s the connection. J Psychiatr Pract. 2006;12(1):41-45.

4. Preskorn, SH. Drevets, WC. Neuroscience basis of clinical depression: implications for future antidepressant drug development. J Psychiatr Pract. 2009;15(2):125-132. ❒

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