Tuesday, October 20, 2020

Study Identifies Predictors of Treatment-Resistant Schizophrenia, Clozapine-Resistant Schizophrenia

A study out of Hong Kong that tracked patients with first-episode psychosis over a 12-year period points to several characteristics of patients that may predict those most likely to develop treatment-resistant schizophrenia. As described in the report in Schizophrenia Bulletin, such characteristics include age, duration of untreated symptoms, and social function.

“Specific interventions including relapse prevention and early initiation of clozapine during the early course of illness may reduce the rate of [treatment-resistant schizophrenia] and improve patient outcomes,” wrote Sherry Kit Wa Chan, M.B.B.S., of the University of Hong Kong and colleagues.

Using a hospital database in Hong Kong, the researchers identified 617 patients with a diagnosis of first-episode schizophrenia-spectrum disorders enrolled in early intervention services. These patients were matched by sex, diagnosis, and age with 617 patients with first-episode psychosis who had received standard care services. Outcomes in these patients were tracked for 12 years.

Patients were considered to have treatment-resistant schizophrenia if they met the following criteria: scored ≥4 on any Positive and Negative Syndrome Scale for Schizophrenia (PANSS) positive symptom item for at least 12 weeks with a moderate functioning impairment (Social and Occupational Functioning Assessment Scale <60) and had a history of at least two trials of antipsychotics above a chlorpromazine equivalent dose of at least 600 mg/d for at least six weeks. Patients were considered to have clozapine-resistant treatment-resistant schizophrenia if they had taken clozapine (350 mg/d) for at least six weeks and continued to score ≥4 on the Clinical Global Impressions Schizophrenia scale and had any PANSS positive symptom item scored ≥4 for at least 12 weeks.

Of the 1,234 patients with first-episode schizophrenia-spectrum disorders followed for 12 years, 13% had been prescribed clozapine, and 15% had treatment-resistant schizophrenia.

An analysis of data on 450 patients—including 157 with treatment-resistant schizophrenia and 293 without treatment-resistant schizophrenia—revealed several differences between these two groups: “Patients with younger age of onset, poorer premorbid social adjustment during adulthood, longer duration of first episode, a greater number of relapses, and a higher level of [daily defined dose] of antipsychotic medication in the first 24 months had an increased risk of developing TRS [treatment-resistant schizophrenia] earlier,” the authors reported.

“Among the TRS patients prescribed clozapine, 25% were clozapine resistant (CR-TRS). The CR-TRS patients had a poorer premorbid social adjustment in late adolescence and longer delay of clozapine initiation compared with non-CR-TRS. CR-TRS had poorer clinical and functional outcomes at 12-year follow-up. Significantly more non-TRS patients died from suicide compared with patients prescribed with clozapine.”

The researchers noted that although the development of treatment-resistant schizophrenia was similar in patients who had received early intervention services and standard care, patients in early intervention services were started on clozapine sooner than those patients in standard care.

For related information, see the Psychiatric News article “More Studies on Duration of Untreated Psychosis Needed.”

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