Diagnostic Psychiatry: Beyond Treatment-Resistant Psychiatric Illnesses

sad girl sitting on couch
sad girl sitting on couch
This article looks at how the vision of diagnostic medicine can be utilized in psychiatry as Diagnostic Psychiatry, according to Lama Muhammad, MD.

Alarmingly, recent studies show that the proportion of all mental health visits to office-based physicians that involved a Not Otherwise Specified (NOS) diagnosis increased significantly along with polypharmacy.1 This raises a common problem in the ambulatory care practice.

Medicine is the art of making excellent differential diagnoses. The art of making an excellent differential diagnosis in medicine resembles the art of Kintsugi. Kintsugi is a Japanese method for repairing broken ceramics with a special lacquer mixed with gold. This can make a broken ceramic piece more precious, valuable, and stronger after repairing. 2 This vision of diagnostic medicine can be utilized in psychiatry as “Diagnostic Psychiatry.” Specific diagnosis and/or precise differential diagnoses lead to better medication choices, therefore improving prognosis. This will eventually lead to fewer treatment-resistant cases as well as lower polypharmacy rates.

Background/Literature Review

The economic burden of major depressive disorder is estimated to be around 200 billion dollars per year.3 However, the impact and burden of treatment-resistant disorders go far beyond the economic cost and the international public health crisis. It is associated with increased morbidity through polypharmacy, side effects of medications, and drug interactions, as well as mortality through suicidality. Yet, research about the diagnoses’ dilemmas and the support of the differential diagnoses’ art lags behind the growing need.4

Despite all the increase in the treatment-resistant disorders research especially for depression, it is clear that something is missing in the definition of treatment-resistant psychiatric disorder. Moreover, relapse data after third-line medications, augmentation therapy, or even electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) procedures can strongly argue against focusing first on the management of such cases.

Lama Muhammad, MD

There are fundamental rates of long-term unresolved morbidity in treated MDD patients, which might be one of the main causes leading to treatment-resistant nature and relapse.5

In multiple psychiatric disorders the common definition of “treatment-resistant disorder” is an inadequate response to at least 2 medications, with adequate doses and appropriate treatment times. Apparently, this definition has focused on pharmacotherapy and missed the fundamental need to capture the vital differential diagnoses dilemmas.6 Diagnostic psychiatry uncovers the roots of the problem before jumping to the management. This art of diagnostic medicine starts with precise differential diagnoses, takes into consideration the medical co-morbidities, and the hidden causes of psychiatric symptoms.

Understanding the problem well enough leads to perceived solutions. While documentation and sitting in front of computers is taking hours from the providers’ time and can lead to burnout7, more efforts are required to enhance accurate diagnoses.

Psychiatrists should give enough time for the diagnostic interview and order neuro and/or physical exams if needed, in addition to ordering appropriate laboratory tests and neuroimaging. For example, in some cases, polypharmacy cannot be avoided, but we can practice rational instead of indiscriminate polypharmacy.8 Diagnostic psychiatry can help in this process by enhancing logical clinical reasoning thinking by getting to the roots of the mental health problem and uncovering possible occult comorbidity or correcting the diagnosis.

Diagnostic Psychiatry Clinic

Opening a diagnostic psychiatry clinic (Table 1) that deals with the co-morbid complex consults from other specialties and gives a second opinion for psychiatric “treatment-resistant cases” which will directly help the academic clinical excellence mission. Moreover, such a clinic will help trainees learning how to handle complex cases by learning more about the art of diagnostic psychiatry.9

While the common approach in treatment-resistant cases is to change the medication, the approach in diagnostic psychiatry is to have difficult to treat disorders or polypharmacy go through the following process:

  1. Reconsider the diagnosis.
  2. Uncover any medical reason for the psychiatric symptoms.
  3. Determine if a new diagnosis has emerged since the original consultation.

(Table 1)

VariableTraditional PsychiatryDiagnostic Psychiatry
Main GoalManage mental illnesses-Diagnosis clarification.
-Second opinion for treatment resistant psychiatric disorders cases.-Medically complicated cases.
Interview focusPsychopathologyPhysical and neuro exam when needed. 
Differential DiagnosesPsychiatric illnessesPsychiatric and medical illnesses.
OrdersLabs and imaging are unlikelyLabs and imaging are common
TreatmentsPsychiatric medications and short-term psychotherapies.Psychiatric medications, in addition to medications that target the medical illness.
VisitsLong term1-3 visits
Target patientsPatients with mental illness-Patient with treatment resistant psychiatric illness. 
-Patient with comorbid complicated medical diagnosis
Interview durationFirst time visits 1 hour for attendings.
1.5 hours for residents. 
Follow up visits: 30 min
First time visits: 1.5 hours for attendings.
2 hours for residents. 
Follow up visits: 45 min

Aims for Diagnostic Psychiatry Outpatient Clinics

  • Improving patients’ experience of care.
  • Improving the health of populations.
  • Reducing morbidities and mortalities.
  • Improving providers’ experience.
  • Teaching trainees how to handle “treatment resistant disorders” and medically complicated cases.
  • Reduced cost of treatment resistant and medically complicated cases.
  • Efforts for recruitment.

Diagnostic Psychiatry Clinic Stakeholders

  1. Patients: With medically complicated cases and with “treatment resistant” disorders
  2. Providers: Psychiatric providers and providers from other specialties.
  3. Trainees: Residents (psych, combined family- psych, family medicine, neurology, internal medicine, rheumatology, dermatology), nurse practitioner students.
  4. Employers 
  5. Payers

Exclusion Criteria in a Diagnostic Psychiatry Clinic

  1. Patients under 18 years old.
  2. Patients with delirium and/or with acute medical illness. (These patients should be sent to the Emergency Department (ED)).
  3. Active SI/HI. (Send to the ED.)
  4. Gravely disabled patients. (Send to the ED.)
  5. Patients with active severe substance use problems. (First refer to an addiction disorder clinic.)
  6. Patients with major neurocognitive disorder (Refer to a geriatric psychiatric clinic.)
  7. Pregnancy (Refer to a women’s clinic.)
  8. Patients with chronic history of primary psychotic disorder and/or on chronic injectable antipsychotics.
  9. Patients with anti-social personality disorder.


The recent increase of rates of psychiatric medications polypharmacy and “treatment-resistant disorders” in parallel with the rise of unspecified psychiatric diagnoses raise concerns about the thoroughness of psychiatric differential diagnoses and the fundamental need for diagnostic psychiatry as a forgotten field.

The novel project of opening a diagnostic psychiatry outpatient clinic fulfills the clinical, academic, and research missions of academic facilities. Moreover, the needs in the community justify the start of such outpatient clinic.


  1. Rajakannan T, Safer DJ, Burcu M, Magno Zito J. National trends in psychiatric not otherwise specified (NOS) diagnosis and medication use among adults in outpatient treatment. Psychiatr Serv. Published online November 16, 2015. doi:10.1176/appi.ps.201500045
  1. Buetow S, Wallis K. The beauty in perfect imperfection. J Med Humanit. 2017;40(3):389-394. doi:10.1007/s10912-017-9500-2
  1. Quantifying the Cost of Depression. Center for Workplace Mental Health. American Psychiatric Association Foundation. http://www.workplacementalhealth.org/Mental-Health-Topics/Depression/Quantifying-the-Cost-of-Depression. Published January 2016. Accessed February 19, 2021.
  1. McIntyre RS, Filteau, MJ, Martin L, et al. Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord. 2014;156:1–7. doi:10.1016/j.jad.2013.10.043
  1.  Forte A, Baldessarini RJ, Tondo L, Vázquez GH, Pompili M, Girardi P. Long-term morbidity in bipolar-I, bipolar-II, and major depressive disorders. J Affect Disord. 2015;178:71-78. doi:10.1016/j.jad.2015.02.011
  1.  Demyttenaere K. What is treatment resistance in psychiatry? A “difficult to treat” concept. World Psychiatry. 2019;18(3):354-355. doi:10.1002/wps.20677
  1. Patel RS, Bachu R, Adikey A, Malik M, Shah M. Factors related to physician burnout and its consequences: A review. Behav Sci (Basel). 2018;8(11):98. doi:10.3390/bs8110098
  1. Kukreja S, Kalra G, Shah N, Shrivastava A. Polypharmacy in psychiatry: A review. Mens Sana Monogr. 2013;11(1):82-99. doi:10.4103/0973-1229.104497
  1. Sibbald M, de Bruin ABH, Cavalcanti RB, van Meerienboer, JJG. Do you have to re-examine to reconsider your diagnosis? Checklists and cardiac exam. BMJ Qual Saf. 20132;22(4):333-8. doi:10.1136/bmjqs-2012-001537