title: Generic Olanzapine Substitution in Patients With Schizophrenia: Assessment of Serum Concentrations and Therapeutic Response After Switching.
abstract: BACKGROUND
  Several reports of loss of efficacy or adverse effects have been described after generic substitution of antipsychotics. To date, studies comparing serum drug levels in patients switched to generic antipsychotics in a standard clinical setting are lacking. The aim of this study was to investigate if switching to generic olanzapine in patients affected by schizophrenia is associated with differences in its serum concentrations and therapeutic response.
  
  
  METHODS
  Preswitching and postswitching serum olanzapine concentrations were compared in schizophrenic outpatients who were switched from a chronic treatment with branded olanzapine to the same dose of its generic alternative. The Positive and Negative Syndrome Scale was concurrently administered to assess modifications in schizophrenia symptom control.
  
  
  RESULTS
  A total of 25 patients (13 women and 12 men, mean age 41.2 ± 12.8 years) concluded the study. Mean olanzapine dose was 12.2 ± 5.4 mg/d. The mean olanzapine serum concentrations decreased from 27.7 ± 14.4 ng/mL during treatment with the branded formulation to 22.6 ± 12.3 ng/mL after switching to the generic formulation (P < 0.01). The log-transformed ratio of generic/brand-name olanzapine serum concentration at steady state was 0.81 (90% confidence interval: 0.72-0.91). The total Positive and Negative Syndrome Scale scores did not significantly change after switching from branded to generic formulation (49.6 ± 8.3 versus 48.6 ± 9.5, P = 0.777). No patient exhibited disease relapse or required dose adjustment after switching.
  
  
  CONCLUSIONS
  Significantly lower serum olanzapine concentrations were found after switching from branded to generic olanzapine. Although these modifications did not significantly impair schizophrenia symptoms control, it cannot be excluded that a longer exposure to lower olanzapine serum concentrations may result in relapse of schizophrenic symptoms. Generic substitution should be considered as an indication for therapeutic drug monitoring in psychiatry.
authors.affiliation: *Department of Clinical and Experimental Medicine; and †Section of Psychiatry, Department of Neurosciences, University of Messina, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Italiano
authors.forename: Antonio
authors.initials: A
authors.lastname: Bruno
authors.forename: Vincenza
authors.initials: V
authors.lastname: Santoro
authors.forename: Giulia
authors.initials: G
authors.lastname: Lanza
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Muscatello
authors.forename: Rocco
authors.initials: R
authors.lastname: Zoccali
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D057915:Drug Substitution; D016568:Drugs, Generic / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D016568:Drugs, Generic; D001569:Benzodiazepines; D000077152:Olanzapine