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Working group develops criteria for treatment-resistant schizophrenia diagnosis, terminology

The Treatment Response and Resistance in Psychosis working group recently published recommendations for diagnostic and terminology criteria for treatment-resistant schizophrenia.

“Lack of uniformity in the definition of treatment resistance also has an impact on clinical guidelines that seek to distill the evidence from studies. Not surprisingly, given the variation in criteria used in the studies, treatment guidelines use vague definitions that are open to a wide range of interpretations, potentially leading to inconsistent clinical management and treatment delays,” Oliver D. Howes, MRCPsych, PhD, of King’s College London, and colleagues wrote.

To address this issue, the Treatment Response and Resistance in Psychosis (TRRIP) working group was formed to standardize the definition of treatment resistance, aid study design and simplify study result comparisons.

Researchers conducted a systematic review of randomized clinical trials of antipsychotics for treatment-resistant schizophrenia (n = 42) to establish definitions and consensus operationalized criteria.

Half of the included studies did not provide operationalized criteria. Among remaining studies, criteria significantly varied, particularly for symptom severity, prior treatment duration and antipsychotic dosage thresholds.

The group identified minimum and optimal requirements for symptom assessment, severity, duration, subjective distress functioning; adequate treatment duration, dosage, number of antipsychotics, current adherence; symptom domain; time course; and ultra-treatment resistant. Minimum requirements for treatment-resistant schizophrenia included:

• interview with standardized rating scale, the Positive and Negative Syndrome Scale for Schizophrenia, Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms or Scale for the Assessment of Positive Symptoms;
• at least moderate symptom severity;
• duration of at least 12 weeks;
• at least moderate functional impairment indicated by a validated scale, such as the Social and Occupational Functioning Assessment Scale;
• information from patient/carer reports, staff and case notes, pill counts and dispensing charts for past-response assessment;
• treatment duration of at least 6 weeks at a therapeutic dosage, with record of minimum and mean duration for each treatment episode;
• dosage equivalent to at least 600 mg of chlorpromazine per day;
• at least two past adequate treatment episodes with different antipsychotics;
• at least 80% of current prescribed doses taken;
• positive, negative and cognitive symptom domains;
• within one year of treatment onset constitutes early onset; 1 to 5 years after treatment onset constitutes medium-term onset; and more than 5 years constitutes late onset; and
• to be considered ultra-treatment resistant to clozapine, individuals must meet above criteria for resistance plus fail to respond to adequate clozapine treatment.

“Treatment-resistant schizophrenia is a major clinical problem, and clinical guidelines throughout the world recommend specific treatments for affected individuals,” the researchers wrote. “We have developed operationalized criteria to address this issue based on a process of wide consultation and refinement, involving expert researchers and clinicians, scientists from the pharmaceutical industry, and other specialists who are active in the field. It is intended that these criteria provide benchmarks to aid study design and reporting, as well as research on the neurobiology of more homogeneously defined subgroups and the development of novel treatment strategies.” – by Amanda Oldt

Disclosure: Howes reports receiving investigator-initiated research funding from or participating in advisory or speaker meetings organized by AstraZeneca, Autifony, Bristol-Myers Squibb, Eli Lilly, Heptares, Janssen, Lundbeck, Leyden-Delta, Otsuka, Servier, Sunovion, Rand, and Roche. Please see the study for a full list of relevant financial disclosures.