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The American Journal of Managed Care December 2013
Implementing Effective Care Management in the Patient-Centered Medical Home
Catherine A. Taliani, BS; Patricia L. Bricker, MBA; Alan M. Adelman, MD, MS; Peter F. Cronholm, MD, MSCE, FAAFP; and Robert A. Gabbay, MD, PhD
Cost Utility of Hub-and-Spoke Telestroke Networks From Societal Perspective
Bart M. Demaerschalk, MD, MSc; Jeffrey A. Switzer, DO; Jipan Xie, MD, PhD; Liangyi Fan, BA; Kathleen F. Villa, MS; and Eric Q. Wu, PhD
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Generic Initiation and Antidepressant Therapy Adherence Under Medicare Part D
Yuhua Bao, PhD; Andrew M. Ryan, PhD; Huibo Shao, MS; Harold Alan Pincus, MD; and Julie M. Donohue, PhD
Impact of Electronic Prescribing on Medication Use in Ambulatory Care
Ashley R. Bergeron, MPH; Jennifer R. Webb, MA; Marina Serper, MD; Alex D. Federman, MD, MPH; William H. Shrank, MD, MSHS; Allison L. Russell, BA; and Michael S. Wolf, PhD, MPH
Medication Utilization and Adherence in a Health Savings Account-Eligible Plan
Paul Fronstin, PhD; Martin-J. Sepulveda, MD; and M. Christopher Roebuck, PhD, MBA
Characteristics of Low-Severity Emergency Department Use Among CHIP Enrollees
Justin Blackburn, PhD; David J. Becker, PhD; Bisakha Sen, PhD; Michael A. Morrisey, PhD; Cathy Caldwell, MPH; and Nir Menachemi, PhD, MPH
Collection of Data on Race/Ethnicity and Language Proficiency of Providers
David R. Nerenz, PhD; Rita Carreón, BS; and German Veselovskiy, MS
Dietary Diversity Predicts Type of Medical Expenditure in Elders
Yuan-Ting Lo, PhD; Mark L. Wahlqvist, MD; Yu-Hung Chang, PhD; Senyeong Kao, PhD; and Meei-Shyuan Lee, DPH

Generic Initiation and Antidepressant Therapy Adherence Under Medicare Part D

Yuhua Bao, PhD; Andrew M. Ryan, PhD; Huibo Shao, MS; Harold Alan Pincus, MD; and Julie M. Donohue, PhD
This study shows that generic initiation improves adherence to antidepressant therapy among Medicare patients and mitigates the negative effects of the Part D coverage gap.
In all analyses, we controlled for patient demographics (age, sex, race/ethnicity), measures of patient disease burden (indicators of  9 comorbid chronic condition categories based on the Chronic Condition Data Warehouse definition21 and the natural log of total  prescription drug spending in 2007), and the specialty of the clinician associated with the index clinical encounter that established  the new depression diagnosis (primary care, mental health specialty, or other medical specialty).


Of the 16,778 patients in our study sample, 65% received LIS in 2007 compared with a national average of 36%,16 reflecting the  substantially lower socioeconomic status of patients with depression (Table 1). Close to 50% of LIS patients were entitled to  Medicare because of disability rather than old age compared with 11% among the non-LIS sample. The LIS sample was less likely  to be white and had a greater number of comorbid conditions. Total prescription drug costs in 2007 for the 2 cohorts receiving LIS  were 2 to 3 times higher than those for the non-LIS cohorts with the same entitlement status. Patients receiving LIS were also more likely to have received their depression diagnosis from a mental health specialist and less likely to have received it from a primary care clinician. Of the non-LIS patients, 30% of the aged transitioned into the coverage gap during the 180-day follow-up compared with 25% of the disabled


The rate of generic initiation ranged from 62% to 68% across the 4 patient cohorts. Of all patients with generic initiation, 11.6% switched to a branded antidepressant within  180 days, while 30.6% of patients with an initial branded antidepressant switched to generics, indicating strong persistence of generic (or branded) choice throughout treatment episode and significance of the initial drug choice. Mean out-of-pocket cost for a 30-day supply of antidepressants was substantially lower for generic versus branded antidepressant initiations: for LIS patients, it was $1.00 if generic compared with $3.71 if branded; for non-LIS patients, it was $6.78 if generic compared with $35.78 if branded.

Antidepressant Disruption

Rate of disruption in antidepressant therapy ranged from 29.3% (95% confidence interval [CI], 28.1%-30.4%) among the LIS, aged patients to 39.3% (95% CI, 35.6%-43.1%)  among the non-LIS, disabled patients (Table 1). Figures 1A and 1B show unadjusted Kaplan-Meier survival curves by patient disability status and generic status of first antidepressant for LIS and non-LIS patients, respectively. Both  fi gures show a sharp increase in disruption (decline in the survival curves) at 30 days after antidepressant initiation. Among the LIS patients (Figure 1A), a greater proportion of disabled patients with generic initiation had a disruption in   antidepressant therapy at 30 days; their survival curve was below those of the other 3 groups for the rest of the follow-up. Among the  non-LIS patients (Figure 1B), survival curves for all 4 groups traced each other closely until around the 120th day, when disabled  patients who initiated therapy with a branded antidepressant started to experience a greater risk of disruption.

Tests of the proportional hazard assumption indicated no evidence of violation of the assumption in any of the Cox models we  estimated. Results (Table 2) show that generic initiation was associated with a lower hazard of treatment disruption across all 4  cohorts. Among LIS patients, the hazard ratio (HR) for generic initiation was 0.88 (95% CI, 0.79-0.98; P = .020) for the aged and  0.84 (95% CI, 0.75- 0.93; P = .001) for the disabled. For the non-LIS patients, HRs for generic initiation were lower: 0.78 (95% CI,  0.70- 0.87; P <.001) among the aged and 0.71 (95% CI, 0.53-0.96; P = .025) among the disabled. The HR associated with the coverage gap was 2.05 (95% CI, 1.18-3.55; P = .010) among the non-LIS, disabled patients. The HRs for the interaction between generic initiation and the coverage gap were below 1 in both analyses but not statistically significant.

Monthly Antidepressant Possession

As depicted in Figures 2A and 2B, all 4 cohorts experienced sharp declines in monthly possession from the first to the second  month. The non-LIS, disabled patients with a branded initiation began to experience a sharper decline in possession in the fourth month, leading to 2 to 4 fewer days of possession in month 6 compared with the other 3 cohorts (Figure 2B).

Based on the mixed-effects models (Table 3), generic initiation was associated with a small but statistically significant increase in monthly possession in all 4 cohorts: 0.6 days (95%  CI, 0.2-1.0; P = .003) for the LIS, aged patients and 0.7 days (95% CI, 0.3-1.1; P <.001) for the LIS, disabled patients; 0.9 days (95% CI, 0.5-1.4; P <.001) for the non-LIS, aged patients and 2.1 days (95% CI,  0.7-3.4; P <.001) for the non-LIS, disabled patients. For the non-LIS, aged patients, experiencing the coverage gap was not  significantly associated with reductions in monthly possession except for the third month in the coverage gap (1.1 fewer days, 95%  CI, –2.2 to 0.0; P = .045). For the disabled, however, the coverage gap had a significant effect while patients were experiencing the second complete month (–4.1 days, 95% CI, –6.6 to –1.7; P = .001) and third complete month (–4.1 days, 95% CI, –7.2 to –1.0; = .001) in the coverage gap. Generic initiation was associated with an additional increase in monthly possession among non-LIS patients experiencing the coverage gap. For example, for disabled patients, generic initiation was associated with an additional 4.1  days (95% CI, 0.4-7.8; P = .032) of possession when patients were experiencing the second month in the coverage gap.

Sensitivity analyses that included non-LIS patients who were experiencing the coverage gap at antidepressant initiation and those  who later transitioned into catastrophic coverage yielded consistent results regarding the effect of generic initiation for both  outcomes, although effects of the coverage gap on adherence were slightly weaker in this larger sample. Sensitivity analysis that  was limited to SSRI initiations only estimated comparable effect sizes for generic initiation with larger CIs.


Across 4 cohorts of fee-for-service Medicare beneficiaries newly diagnosed with depression and treated with antidepressants in  2007, we found that initiating the therapy with a generic antidepressant was consistently associated with increased medication  adherence. This effect was stronger among the 2 non-LIS cohorts and strongest among the non- LIS, disabled cohort. Generic initiation increased the likelihood of monthly antidepressant possession while non-LIS patients were experiencing the Part D  coverage gap. 

Previous studies have linked out-of-pocket cost differentials between generic and branded medications to substantially increased adherence among patients starting with a generic medication for several chronic medical conditions.9 Our results suggest that beneficial effects of generic use apply to antidepressant therapy as well. However, such benefits may vary across patient populations. For example, a recent study of commercially insured patients did not find generic initiation to be associated with a greater likelihood of refill of the initially prescribed antidepressant.22 The consistent benefits of generic initiation found in our study,  regardless of LIS status, may reflect the lower socioeconomic status of depressed Medicare beneficiaries and their greater sensitivity to cost differentials between generic and branded drugs. Our findings thus lend strong support for generic initiation as a

means to improve antidepressant adherence among Medicare patients.

Our findings also suggest that while the Part D coverage gap may be detrimental to antidepressant adherence, the benefits of generic initiation may mitigate the negative effects. Disabled patients not receiving LIS may be especially vulnerable to increased out-of-pocket cost during the coverage gap,  and they appear to benefit most from the protective effect of generic initiation.

About half of the disruption in antidepressant therapy across all patient cohorts occurred at 30 days after initiation, which, for most  patients, also marked the end of the first prescription. Myriad factors may underlie the dramatic decline in adherence by the end of  the first month. Benefi ciaries may discontinue medication due to lack of response, side effects, and/or a lack of continued  medication management (dose titration, medication switch, or augmentation). Physicians may not have adequately educated  patients on antidepressant treatment when prescribing the medication and/or may not have followed up with sufficient intensity. Medication management accompanied by systematic clinical assessment may be important to further improve adherence.23

In our unadjusted analysis of the LIS cohorts, disabled patients with generic initiation were shown to have worse adherence compared with disabled patients with branded initiation, which was inconsistent with findings of the adjusted analysis. Disabled  atients receiving LIS were particularly vulnerable to socioeconomic disadvantages that were positively associated with generic  initiation, but at the same time, negatively associated with adherence. In an unadjusted analysis, confounding by these factors may  have outweighed the effect of generic initiation.

One limitation of our study is that we are unable to measure all of the clinical characteristics of patients that may influence choice of  branded versus generic antidepressant. For example, clinicians may have selectively prescribed branded antidepressants to  patients whom they perceived as having a greater risk of nonadherence if started on older generic drugs. However, we do not believe  this is likely to bias our estimates, for several reasons. First, recent evidence shows very similar efficacy and side effect profiles  among secondgeneration antidepressants (including the branded drugs seen in this study).24 For a given patient who is treatment  naïve, clinicians have little basis for predicting whether one antidepressant would be more effective or tolerable than another, especially among the second-generation classes.25 Thus, clinician choice of branded versus generic initiation based on clinical   characteristics may be quite limited. Second, previous studies have consistently shown that provider preferences are a much  stronger determinant of medication choice than are patient clinical needs; generic initiation status may largely reflect prescriber and  patient familiarity with the drug chosen and affordability to the patient.26-28 

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