title: Medication Adherence and Persistence in Patients with Severe Major Depressive Disorder with Psychotic Features: Antidepressant and Second-Generation Antipsychotic Therapy Versus Antidepressant Monotherapy.
abstract: BACKGROUND
  Major depressive disorder with psychotic features, or psychotic depression, is a severe mental health disorder often associated with a worse depression-related symptom profile when compared with major depressive disorder without psychotic features. While combination pharmacotherapy with an antidepressant and an antipsychotic is recommended as first-line therapy, antidepressant monotherapy has been found to be useful and efficacious in psychotic depression.
  
  
  OBJECTIVE
  To assess the rates of antidepressant adherence and antidepressant persistence in Texas Medicaid patients with psychotic depression who used antidepressant plus second-generation antipsychotic (AD/SGA) therapy or antidepressant (AD) monotherapy.
  
  
  METHODS
  Using Texas Medicaid prescription and medical claims data from September 2007 to December 2012, adult patients aged 18-63 years were included if they had no confounding psychiatric disorders, no antidepressant claims during a 6-month pre-index period, and at least 1 diagnosis for severe major depressive disorder with psychotic features (ICD-9-CM codes 296.24 and 296.34). The first claim date for an antidepressant served as the index date. All patients were required to have at least 2 antidepressant claims, and those in the AD/SGA cohort were required to have 2 or more claims for an SGA. Study covariates included age, gender, race/ethnicity, residence, Charlson Comorbidity Index (CCI) score, and tobacco use/dependence. Statistical analyses included descriptive statistics, univariate analyses, logistic regression, and Cox proportional hazards regression.
  
  
  RESULTS
  A total of 926 patients met study criteria (AD cohort = 510; AD/SGA cohort = 416). The overall sample had a mean [±SD] age of 40.5 [±13.2] years and was primarily female (66.8%) and non-Caucasian (74.8%). When compared with the AD cohort, patients in the AD/SGA cohort had a 52.3% higher likelihood of being adherent to antidepressant therapy based on proportion of days covered (PDC; OR = 1.523; 95% CI = 1.129-2.053; P = 0.006). Similarly, antidepressant adherence was 42.0% higher for the AD/SGA cohort based on medication possession ratio (MPR; OR = 1.420; 95% CI = 1.062-1.898; P = 0.018). Younger patients, African Americans, and tobacco users/dependents had significantly worse likelihoods of antidepressant medication adherence based on PDC and MPR. The risk of antidepressant nonpersistence was 23.2% lower for patients in the AD/SGA cohort (HR = 0.768; 95% CI = 0.659-0.896; P = 0.001), compared with those in the AD cohort. Antidepressant nonpersistence was significantly higher in younger patients, African Americans, Hispanics, and tobacco users/dependents.
  
  
  CONCLUSIONS
  Better antidepressant adherence and persistence outcomes were associated with combination pharmacotherapy with an AD and an SGA antipsychotic. This study provides real-world estimates that support the current first-line treatment recommendations for psychotic depression; however, it should be noted that the majority of study patients used AD therapy only. Future research in psychotic depression is needed.
  
  
  BACKGROUND
  Kim-Romo received funding to conduct this study from the PhRMA Foundation Pre-Doctoral Fellowship in Health Outcomes. Rascati, Richards, Ford, Wilson, and Beretvas declare no conflict of interest in relation to this manuscript. Kim-Romo and Rascati collaborated on the study design, data analysis, study interpretation, and writing of this manuscript. Richards, Ford, Wilson, and Beretvas provided critical evaluation of the study design, analysis, and interpretation, as well as edited this manuscript.
authors.affiliation: 1 Health Outcomes & Pharmacy Practice, College of Pharmacy, The University of Texas at Austin.
authors.forename: Dawn N
authors.initials: DN
authors.lastname: Kim-Romo
authors.affiliation: 1 Health Outcomes & Pharmacy Practice, College of Pharmacy, The University of Texas at Austin.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Rascati
authors.affiliation: 2 Center for Pharmacoeconomic Studies, College of Pharmacy.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Richards
authors.affiliation: 1 Health Outcomes & Pharmacy Practice, College of Pharmacy, The University of Texas at Austin.
authors.forename: Kentya C
authors.initials: KC
authors.lastname: Ford
authors.affiliation: 1 Health Outcomes & Pharmacy Practice, College of Pharmacy, The University of Texas at Austin.
authors.forename: James P
authors.initials: JP
authors.lastname: Wilson
authors.affiliation: 3 Research and Graduate Studies, College of Education, The University of Texas at Austin.
authors.forename: Susan N
authors.initials: SN
authors.lastname: Beretvas
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D038801:International Classification of Diseases; D016015:Logistic Models; D008297:Male; D008484:Medicaid; D012189:Retrospective Studies; D014481:United States; D016903:Drug Monitoring
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents