Antipsychotic treatment response worsens in relapses following response in first episode schizophrenia

Treatment-resistant schizophrenia (TRS) is increasingly being recognized as a focus area in psychiatric research. A poster by Hiroyoshi Takeuchi et al., Toronto, Canada, presented at SIRS 2018 compared trajectories of antipsychotic medication responses before and after relapse following initial response in a large sample of patients with first episode schizophrenia (FES) or schizoaffective disorder to determine whether relapse contributes to treatment resistance.

Data from patients with schizophrenia (n=126) and schizoaffective disorder (n=4) were collected during routine clinical care and were analyzed retrospectively. Patients included in the study were those with FES or schizoaffective disorder who met the following ordered criteria:

  • referral to the First-Episode Psychosis Program between 2003 and 2013
  • were prescribed treatment with an oral second-generation antipsychotic according to a standardized treatment algorithm post-first relapse
  • achieved positive symptom remission
  • had a subsequent relapse (i.e., second episode) in association with non-adherencea
  • had been retreated with a second-generation antipsychotic post-second relapse

All patients were prescribed the same antipsychotic medication over the course of 12 weeks in both episodes

All patients were prescribed the same antipsychotic medication over the course of 12 weeks following both psychotic episodes. Those responding sub-optimallyb were thereafter offered an antipsychotic medication with a different mode of action.

Antipsychotic treatment response was assessed using changes in the Brief Psychiatric Rating Scale (BPRS) total and positive symptom scores. It also included the number of patients who achieved positive symptom remission and 20% and 50% positive symptom response.

Antipsychotic medication doses in the second episode were significantly higher than those in the first episode (p=0.03)


A total of 130 patients were included in the analyses, 96.9% of whom had been diagnosed with schizophrenia. Their mean age was 22.1 ± 3.1 years. The majority of patients were male (86.9%), Caucasian (67.7%) and unmarried (96.2%). The mean duration between the first and second psychotic episodes was 19.3 ± 9.7 months.

Antipsychotic treatment response is reduced or delayed should relapse occur following effective treatment of FES

Over a 59-week period, the change in positive symptom remission rates were statistically significantly greater in the first episode compared to the second (>0.01) during the early weeks of treatment. Additionally, 20% and 50% response rates were attained more quickly in those with first compared to second episode psychosis.  The rate of attainment of 50% response rates over the course of the study was statistically significantly lower in second compared to first episode patients over the 59-week period.

Together these findings suggest that antipsychotic medication treatment response is reduced or delayed should relapse occur following effective treatment of FES.

adefinition of adherence was not provided

bdefinition of what comprised sub-optimal response was not provided

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