Expert Group Proposes Consensus Criteria for Determining Treatment-Resistant Schizophrenia

An international group of experts has proposed consensus criteria for determining when schizophrenia is “treatment resistant.” The criteria are described in a report appearing in AJP in Advance today.

More standardized criteria in clinical trials could aid in the development of better treatments for patients with refractory schizophrenia, according to the authors of the paper. 

The criteria were formed by the Treatment Response and Resistance in Psychosis (TRRIP) working group, an international group of more than 50 experts on schizophrenia and treatment resistance. The group performed a systematic review of definitions of treatment-resistant schizophrenia used in randomized antipsychotic clinical trials. They found wide variation in criteria that were used to define treatment resistance, particularly in the domains of symptom severity, prior treatment duration, and antipsychotic dosage thresholds; only two studies used the same criteria.

To address this variation, the working group developed “consensus criteria” specifying minimum and optimal criteria for each domain. A few of the domains and their optimal criteria for determining treatment resistance include the following: 

• Symptom severity and change: Treatment-resistant patients’ symptoms should be at least moderately severe, as defined on a standardized rating scale such as the Positive and Negative Syndrome Scale. They should experience less than 20% symptom reduction, also using a standardized rating scale, during a prospective trial or observation of six or more weeks.
• Functioning: Treatment-resistant patients should be determined to have at least moderate functional impairment, measured using a validated scale such as the Social and Occupational Functioning Scale.
• Past treatment: Treatment-resistant patients should have experienced at least two past unsuccessful treatment episodes with different antipsychotic drugs, of at least six weeks duration at a therapeutic dosage for both trials.
• Dosage: Treatment-resistant patients should have received a therapeutic dose in previous medication trials equivalent to at least 600 mg of chlorpromazine per day. 

“The management of treatment resistance remains a real clinical challenge,” John Kane, M.D. (pictured above), a co-chair of the working group, told Psychiatric News. “I think we need to focus a lot more of our research energy on how we can better serve those patients who don’t respond adequately to the medications we have. A key goal [of the proposed criteria] is to help advance efforts to provide help to these patients by conducting more and better designed research in those people who are treatment resistant.”

For related information, see the Psychiatric News article “Clozapine Use Varies From State to State.”

(Image: Courtesy of John Kane, M.D.)