Early Diagnosis Can Improve Outcomes in Treatment-Resistant Schizophrenia

Different clinical and neurobiologic pathways may be involved in treatment-resistant schizophrenia as it is not a homogeneous subgroup within the schizophrenia spectrum.
The following article is part of live conference coverage from the 2017 Psych Congress in New Orleans, Louisiana. Visit MPR‘s conference section for continuous coverage live from Psych Congress 2017.

NEW ORLEANS — Early diagnosis of treatment-resistant schizophrenia (TRS) can significantly improve outcomes for patients, according to research presented at the 2017 Psych Congress poster session.1

A team of researchers led by John M. Kane, MD, professor and chairman of the Department of Psychiatry at the Hofstra Northwell School of Medicine, Hempstead, New York, summarized the results of a June 2017 roundtable that sought to clarify the definition of TRS and identify current treatment options. 

Schizophrenia affects nearly 1% of the US population, and an estimated 21 million individuals are affected worldwide.2 Approximately 30% of patients diagnosed with schizophrenia have TRS. The definition of treatment resistance varies among various guidelines in place by the American Psychiatric Association (APA),3 the National Institute for Health and Care Excellence (NICE),4 the World Federation of Societies of Biological Psychiatry (WIFSBP),5 and Treatment Response and Resistance in Psychosis (TRRIP) Working Group.6 Following review of the numerous guidelines reported, the consensus of the roundtable panel members for a definition of TRS was treatment failure on any 2 antipsychotic agents administered at an adequate dosage (ie, equivalent to chlorpromazine 600 mg/d)6 and duration.

The panel members also identified a set of factors that clinicians should evaluate when considering TRS: inadequate adherence to the treatment regimen; pharmacokinetics associated with the agent; comorbid conditions; and patient care setting.

Comparison of TRS with treatment-responsive schizophrenia identifies numerous clinical, genetic, neurobiologic, or neurocognitive differences between the two types.  Characteristics indicative of TRS include reduced gray matter in the brain, earlier age of onset of schizophrenia, and lower verbal memory scores. 

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The roundtable participants suggested that if a patient’s positive symptoms are not responsive to 2 antipsychotic drugs after a minimum treatment of 12 weeks, clinicians should consider alternative pharmacologic treatments, including clozapine. However, clozapine treatment remains controversial. While earlier treatment with clozapine has been associated with improved outcomes, studies have shown that a relatively low number of patients (≤6%) receive the treatment.7 Studies suggest that psychosocial and electroconvulsive therapies, and repetitive transcranial magnetic stimulation may represent effective adjunctive treatments to pharmacotherapies for patients with TRS.8-11

In certain situations, including when a patient is at high risk for suicide, a treatment duration of 2 weeks may be sufficient before including additional clinical measures (eg, clozapine). All treatment choices should result from a shared decision-making process among the treatment team, the patient, and patient’s family.

Earlier identification of TRS should therefore allow for more informed treatment decisions by the clinicians, patients, and caregivers to reduce the overall burden of schizophrenia.


All of the study’s researchers have received financial support from Lundbeck Inc.

Visit MPR‘s conference section for continuous coverage live from Psych Congress 2017.


1. Kane JM, Agid O, Baldwin ML, et al. Clinical guidance on the identification and management of treatment-resistant schizophrenia. Poster presentation at: Psych Congress; September 16-19, 2017; New Orleans, LA.

2. National Institute of Mental Health.  Schizophrenia.  Available at: https://www.nimh.nih.gov/health/statistics/prevalence/schizophrenia.shtml. Accessed September 19, 2017.

3. Lehman AF, Lieberman JA, Dixon LB. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161(2 Suppl):1-56.

4. NICE. Psychosis and Schizophrenia in Adults: Treatment and Management (Clinical Guideline 178). London: Royal College of Psychiatrists; 2014.

5. Hasan A, Falkai P, Wobrock T. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012;13(5):318-378.

6. Howes OD, McCutcheon R, Agid O, et al. Treatment-resistant schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group consensus guidelines on diagnosis and terminologyAm J Psychiatry. 2017;174(3):216-229.

7. Manuel JI, Essock SM, Wu Y, Pangilinan M, Stroup S. Factors associated with initiation on clozapine and on other antipsychotics among Medicaid enrolleesPsychiatr Serv. 2012;63(11):1146-1149.

8. Wykes T, Steel C, Everitt B, Tarrier N. Cognitive behavior therapy for schizophrenia: effect sizes, clinical models, and methodological rigor. Schizophr Bull. 2008;34(3):523-537.

9. Slotema CW, Bloma JD, Lutterveld R, Hoek HW, Sommerb EC. Review of the efficacy of transcranial magnetic stimulation for auditory verbal hallucinations. Biol Psychiatry. 2014;76(2):101-110.

10. Petrides G, Malur C, Braga RJ. Electroconvulsive therapy augmentation in clozapine-resistant schizophrenia: a prospective, randomized study. Am J Psychiatry. 2015;172(1):52-58.

11. Zheng W, Cao X-L, Ungvari GS. Electroconvulsive therapy added to non-clozapine antipsychotic medication for treatment resistant schizophrenia: meta-analysis of randomized controlled trials. PloS ONE. 2016;11(6)e0156510.

This article originally appeared on Psychiatry Advisor