A predictor model of treatment resistance in schizophrenia using data from electronic health records

Abstract

Objectives: To develop a prognostic tool of treatment resistant schizophrenia (TRS) in a large and diverse clinical cohort, with comprehensive coverage of patients using mental health services in four London boroughs.

Methods: We used the Least Absolute Shrinkage and Selection Operator (LASSO) for time-to-event data, to develop a risk prediction model from the first antipsychotic prescription to the development of TRS, using data from electronic health records.

Results: We reviewed the clinical records of 1,515 patients with a schizophrenia spectrum disorder and observed that 253 (17%) developed TRS. The Cox LASSO survival model produced an internally validated Harrel's C index of 0.60. A Kaplan-Meier curve indicated that the hazard of developing TRS remained constant over the observation period. Predictors of TRS were: having more inpatient days in the three months before and after the first antipsychotic, more community face-to-face clinical contact in the three months before the first antipsychotic, minor cognitive problems, and younger age at the time of the first antipsychotic.

Conclusions: Routinely collected information, readily available at the start of treatment, gives some indication of TRS but is unlikely to be adequate alone. These results provide further evidence that earlier onset is a risk factor for TRS.

Fig 1. Antipsychotic coding process timeline for coding outcome data.

Fig 2. Kaplan-Meier curve of the survival probability for treatment resistant schizophrenia.

Fig 3. Nomogram for Cox Lasso regression to calculate individual normalized prognostic indexes (PI, given by the linear predictor line) for treatment resistant schizophrenia.

Coefficients are based on the Lasso Cox model.—To predict the rate of survival using the nomogram, one can take the example of a 30-year-old patient, with Schizophrenia, having 34 inpatient days recorded at 3 months before the 1st antipsychotic (AP) date, 50 inpatient days recorded 3 months after 1st AP date, 15 community face-to-face days recorded 3 months before 1st AP date, having a minor problem requiring no action and having mood disorders as comorbidity, has a total point score of 78 + 33 + 28 + 6 + 18 + 10 + 0 = 173. This corresponds to a normalized prognostic index of 0.57 (linear predictor line) for TRS, meaning that the patient has a probability to become TRS at 1 year falling in the range 4.14%-7.66%, at 2 years falling in the range 7.62%-13.89%, at 5 years in the range 16.45%-28.74% and at 10 years in the range 26.57%-44.13% (see S3 Table).