Background: Antidepressant monotherapy is effective in achieving treatment remission in only approximately one third of patients with depression, and even switching to a second antidepressant brings the cumulative remission rate to only 50%-55%. This has led to an interest in augmentation therapy for the management of treatment-resistant depression.
Objectives: To assess (a) selective serotonin reuptake inhibitor/selective norepinephrine reuptake inhibitor (SSRI/SNRI) adherence when augmented with second-generation atypical antipsychotics (SGAs) or L-methylfolate using a modified application of the Healthcare Effectiveness Data and Information Set (HEDIS) acute medication management (AMM) measures at the time of augmentation, and (b) the depression-specific and total health care cost, comparing the 2 forms of augmentation therapy in the treatment of depressive disorder.
Methods: Patients with a diagnosis of depression and a pharmacy claim for an SSRI/SNRI between January 1, 2006, and December 31, 2009 (index date), and receiving concomitant augmentation therapy with either an SGA or L-methylfolate (augmentation date), were identified in the MarketScan database and followed for 231 days (follow-up). Patients were excluded for having any pharmacy claim for an antidepressant or SGA 90 days pre-index; having an L-methylfolate claim 6 months pre-index; age < 18 years on the index date; or a diagnosis of pregnancy, dementia, psychotic-related mental disorders, Alzheimer's disease, or Parkinson's disease in the 12-month pre-index period. Propensity score matching (3:1 ratio, atypical antipsychotic to L-methylfolate) was used to select the final study cohorts, using covariates of age, gender, comorbidities, index SSRI/SNRI, and index SSRI/SNRI dose. Adherence to antidepressant therapy was measured from the augmentation date and included a modified application of the HEDIS (mHEDIS) AMM acute and chronic phase measures as well as the 6-month medication possession ratio. Health care utilization and cost were measured for the 6-month postaugmentation period and included both total as well as depression-related utilization/cost. Comparisons between the closely matched SGA and L-methylfolate-augmented cohorts were made using chi-square tests for binary measures and t-tests for continuous measures.
Results: Following propensity score matching, 4,053 SGA and 1,351 L-methylfolate patients were found to have augmentation of the index SSRI/SNRI within 12 months of the index date. The comparison groups were well matched on age, gender, comorbidities, and the type and dose of the SSRI/SNRI being augmented. The most common antidepressants augmented in both groups were escitalopram, duloxetine, and venlafaxine. Mean (standard deviation [SD]) time from index to augmentation was 73.5 [96.7] days for SGA and 105.9 [108.7] days for L-methylfolate (P < 0.001). The most common SGAs utilized for augmentation were quetiapine, aripiprazole, and risperidone. L-methylfolate was primarily dosed at 7.5 mg/day. The mHEDIS AMM acute phase measure was met by 68.7% of the SGA cohort and 78.7% of the L-methylfolate cohort (P < 0.001). The mHEDIS continuation phase measure was met by 50.3% of the SGA cohort and 62.1% of the L-methylfolate cohort (P < 0.001) following augmentation. Medical utilization (inpatient, emergency department, and outpatient) was significantly higher for the SGA group, while total prescription utilization was significantly higher in the L-methylfolate group. Mean [SD] total 6-month postaugmentation costs for the SGA group was $8,499 [$13,585] and $7,371 [$12,404] for the L-methylfolate group (P = 0.005), and 6-month depression-related costs were $2,688 [$4,201] for the SGA group and $1,613 [$2,315] for the L-methylfolate group (P < 0.001).
Conclusions: Patients who augmented SSRI/SNRI therapy with SGA or L-methylfolate achieved mHEDIS AMM acute phase and continuation phase adherence scores of 69%-79% and 50%-62%, respectively. These modified scores exceeded the 2012 national median benchmarks for unmodified HEDIS AMM measures for commercial health plans. In this study, augmentation with L-methylfolate was associated with significantly higher adherence measures compared with augmentation with SGA. In addition, health care utilization and total health care costs, as well as depression-related costs, were significantly lower in the L-methylfolate augmentation group compared with augmentation with SGA.