Evaluating antidepressant treatment prior to adding second-line therapies among patients with treatment-resistant depression

Amany K. Hassan, Kevin C. Farmer, Nancy C. Brahm, Barbara R. Neas

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background Patients with depression can be mistakenly labeled as treatment-resistant if they fail to receive an adequate first-line antidepressant trial. Adding second-line agents to the treatment regimens can create an additional burden on both the patients and the healthcare system. Objectives To determine if depressed patients receive an adequate antidepressant trial prior to starting second-line therapy and to investigate the association between the type of second-line treatment and severity of illness or depression among unipolar versus bipolar patients. Setting Oklahoma Medicaid claims data between 2006 and 2011. Methods Subjects were depression-diagnosed adult patients with at least two prescriptions of antidepressants followed by a second-line agent. Patients were categorized into one of three groups: an atypical antipsychotic, other augmentation agents (lithium, buspirone, and triiodothyronine), or adding antidepressants, based on the type of second-line therapy. An adequate trial was defined per the American Psychiatric Association guidelines. Factors associated with the type of treatment were tested using multinomial logistic regression models stratified by type of depression (unipolar vs. bipolar patients). Main outcome measure Variables used to measure receiving an adequate antidepressant trial included: trial duration, adherence, dose adequacy, and number of distinct antidepressant trials. Results A total of 3910 patients were included in the analysis. Most subjects reached the recommended antidepressant dose. However, 28 % of patients had an antidepressant trial duration <4 weeks and only 60 % tried at least two antidepressant regimens prior to adding second-line therapy. Approximately 50 % of the subjects were non-adherent across all groups. Severity of illness and receipt of an adequate antidepressant trial were not predictors of the type of second-line treatment. Conclusion Many patients do not receive an adequate antidepressant trial before starting a second-line agent. The type of second-line treatment was independent of severity of depression. These findings support policies that require reviewing the recommended dose and duration of the first-line antidepressant before adding second-line agents. Healthcare providers need to review the patient’s history and reconsider the evidence for prescribing second-line agents.

Original languageEnglish
Pages (from-to)429-437
Number of pages9
JournalInternational Journal of Clinical Pharmacy
Issue number2
StatePublished - 1 Apr 2016


  • Adherence
  • Antidepressants
  • Antipsychotics
  • Second-line treatment
  • Treatment-resistant depression
  • United States


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