The evolution of treatment resistance: Biologic implications

Herbert Y. Meltzer*, Myung Lee, Philip Cola

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


The evolution of resistance of positive symptoms to antipsychotic therapy may represent a valuable means of subtyping schizophrenia. In contrast, resistance of negative symptoms and cognitive function to antipsychotic agents seems to be present from the first episode of psychotic symptoms and does not evolve over time to the same extent. If these findings are validated, this clearly points toward differences in the etiology of these compOnents of schizophrenia. Data from a cohort of 223 patients with unsatisfactory responses to classical antipsychotic therapy are evaluated, at least 60% of whom responded to subsequent treatment with clozapine. Comparisons were made between the subgroups of patients with primary and delayed onset treatment resistance. Both subgroups responded to clozapine therapy, although better response was evident for patients with delayed resistance. The withdrawal of clozapine from patients who had previously been respOnsive to classical antipsychotic therapy was capable of inducing treatment resistance.

Original languageEnglish (US)
Pages (from-to)5S-11S
JournalJournal of clinical psychopharmacology
Issue number2 SUPPL. 1
StatePublished - Apr 1998

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)


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