title: Results of a naturalistic study of treatment options: switching atypical antipsychotic drugs or augmenting with valproate.
abstract: BACKGROUND
  Combination therapy with atypical antipsychotic agents has not been well studied. Duration of persistence with a prescribed treatment regimen can be used to estimate overall treatment success.
  
  
  OBJECTIVE
  The aim of this study was to determine whether valproate augmentation improved treatment efficacy (ie, persistence with the prescribed regimen) and efficacy (ie, reduction of antipsychotic dose) with atypical antipsychotic drugs for older and younger patients, using a retrospective database analysis.
  
  
  METHODS
  Prescription refill data for atypical antipsychotics during calendar-year 2001 from a national pharmacy chain was used for longitudinal analyses. The database was used to identify patients aged 15 to 64 years and > or =65 years taking risperidone, quetiapine, or olanzapine (but not valproate). Patients who switched to another atypical antipsychotic (group A) or added valproate (group B) were followed after the index prescription to determine the duration of persistence with the treatment regimen and dose changes.
  
  
  RESULTS
  We identified 10,262 patients who were prescribed an atypical antipsychotic, of whom 1022 patients switched to an alternative atypical and 1651 added valproate to the index atypical. The addition of valproate provided significantly longer duration of treatment regimen (mean, 155-159 days) than switching from any atypical antipsychotic drug (mean, 127-130 days) for patients aged 15 to 64 years or > or =65 years (all P<0.001). Atypical antipsychotic doses did not change significantly from baseline to final prescription in groups A or B. The final mean (SD) dose of valproate added to risperidone (389.1 [130.7] mg/d) was significantly lower than valproate added to quetiapine (424.6 [117.1] mg/d; P=0.002) or olanzapine (411.6 [122.8] mg/d; P=0.007).
  
  
  CONCLUSIONS
  In this naturalistic study, the addition of valproate to an atypical antipsychotic increased the duration of treatment compared with switching among atypical antipsychotics. Valproate augmentation may be a good treatment strategy for patients whose atypical antipsychotic monotherapy is inadequate.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, USA. Joyce.Cramer@Yale.edu
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Cramer
authors.forename: Michael
authors.initials: M
authors.lastname: Sernyak
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D018692:Antimanic Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D003987:Dibenzothiazepines / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy*; D008875:Middle Aged; D000077152:Olanzapine; D000069348:Quetiapine Fumarate; D012189:Retrospective Studies; D018967:Risperidone / Q000627:therapeutic use; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D014635:Valproic Acid; D018967:Risperidone; D000077152:Olanzapine