Adherence and Persistence Across Antidepressant Therapeutic Classes: A Retrospective Claims Analysis Among Insured US Patients with Major Depressive Disorder (MDD)

Abstract

Background: Adherence and persistence to therapy, or how well a patient follows provider directions on frequency and time to discontinuation of prescribed medications, is associated with positive health outcomes, including decreased healthcare costs and patient mortality. A clear literature gap exists assessing adherence and persistence to antidepressants (ADs) in the major depressive disorder (MDD) population at clinically relevant time points and at the therapeutic class level.

Objective: This study assessed adherence and persistence to specific ADs, therapeutic classes, and AD therapy overall at multiple time points among US individuals from commercial, Medicare supplemental, and Medicaid insurance plans.

Methods: Patients with MDD without AD or MDD claims in the prior 6 months who initiated therapy in 2003-2014 with a selective serotonin reuptake inhibitor (SSRI), serotonin and norepinephrine reuptake inhibitor (SNRI), tricyclic AD (TCA), monoamine oxidase inhibitor (MAOI), or other AD were identified using MarketScan^® databases. These databases contain information on diagnoses, billing codes, and dates of service. Adherence (proportion of days covered) and persistence (days until a 30-day gap in therapy) were calculated to AD medication, AD therapeutic class, and AD therapy overall over the first 3, 6, 9, and 12 months from the index prescription date. Multivariable logistic regression estimated the adjusted odds ratios (ORs) of adherence to initial AD medication comparing AD therapeutic classes.

Results: For 527,907 patients, adherence to initial AD medication decreased over 3, 6, 9, and 12 months (41, 31, 24, and 21%, respectively). Similar patterns were observed for adherence to initial AD therapeutic class, AD therapy overall, and all three persistence calculations. The odds of adherence to SNRIs versus SSRIs were 20-27% greater at 3, 6, 9, and 12 months (ORs 1.20, 1.23, 1.25, 1.27, respectively; p-values all <0.0001). Similar or significantly lower odds of adherence were demonstrated for other classes versus SSRIs at 3, 6, 9, and 12 months [ORs for other ADs 0.80, 0.77, 0.74, 0.72, respectively (p-values all <0.0001); ORs for TCAs 0.46, 0.45, 0.47, 0.49, respectively (p-values all <0.0001); ORs for MAOIs 1.13, 1.0, 0.77, 0.69, respectively (p-values all >0.05)].

Conclusion: We found low adherence and persistence to ADs in the MDD population. Within the limitations of the insurance claims data we analysed, our results suggest that adherence may differ based on therapeutic class, as patients initiating SNRI therapy appeared to have a higher likelihood of adherence versus SSRIs over the year assessed, while the odds of adherence appeared similar or lower for other classes versus SSRIs. Further prospective research is needed to confirm these findings and determine additional drivers of these apparent differences by AD therapeutic class.

Fig. 1

Patient selection flowchart. ^aOne inpatient or one outpatient diagnosis with a confirmatory outpatient or inpatient diagnosis within 60 days. ^bThis 6-month period did not include the 60-day period immediately preceding the IDD. ^cIf the IPD was before the IDD, continuous enrollment eligibility was re-evaluated for 6 months prior to the IPD. If the IPD was after the IDD, eligibility was re-evaluated for 12 months post IPD, as defined in the exclusion criteria. ^dAs defined in exclusion criteria. AA adjunctive agent, AD antidepressant, IDD index diagnosis date, IPD index prescription date, MDD major depressive disorder

Fig. 2

Index prescription date identification (a) and identification of relevant prescription claims to calculate adherence and persistence (b). ^aIPD was the first claim for an AD prescription that occurred within 60 days before or after a qualifying MDD diagnosis date. ^bContinuous enrollment assessed principally from the IDD and was then re-assessed from the IPD. b Consider a patient who receives citalopram (first and second prescription; yellow), escitalopram (third prescription; red), and then desvenlafaxine (fourth prescription; blue). Prescription claims relevant to calculations are identified by calculation type: (1) to initial AD medication (yellow prescription claims only), (2) to initial therapeutic class (yellow and red prescription claims only), and (3) to AD therapy overall (yellow, red, and blue prescription claims). AD antidepressant, IDD index diagnosis date, IPD index prescription date, MDD major depressive disorder

Fig. 3

Distribution of index prescriptions by year and initial therapeutic class. AD antidepressant, MAOI monoamine oxidase inhibitor, SNRI serotonin and norepinephrine reuptake inhibitor, SSRI selective serotonin reuptake inhibitor, TCA tricyclic antidepressant

Fig. 4

Adherence (a) and persistence (b) by calculation type over the first 3, 6, 9, and 12 months after index prescription date. AD antidepressant. *p < 0.0001 vs. adherence to 3 months (McNemar’s paired χ ² test of equality of proportions)

Fig. 5

Proportion adherent (a) and persistent (b) to initial antidepressant medication at the first 3, 6, 9, and 12 months after index prescription date, by therapeutic class. AD antidepressant, MAOI monoamine oxidase inhibitor, SNRI serotonin and norepinephrine reuptake inhibitor, SSRI selective serotonin reuptake inhibitor, TCA tricyclic antidepressant. *p < 0.01, **p < 0.0001 vs. adherence to 3 months (McNemar’s paired χ² test of equality of proportions)

Fig. 6

Time to discontinuation of initial antidepressant medication by therapeutic class. AD antidepressant, MAOI monoamine oxidase inhibitor, SNRI serotonin and norepinephrine reuptake inhibitor, SSRI selective serotonin reuptake inhibitor, TCA tricyclic antidepressant. p < 0.0001 comparing therapeutic classes (log-rank test)

Fig. 7

Adjusted odds of adherence at 6 months versus initial selective serotonin reuptake inhibitor therapy^a,b. *p < 0.0001 vs. initial selective serotonin reuptake inhibitor therapy. ^aResults (odds ratios of adherence and 95% confidence intervals) were similar for the 3-, 9-, and 12-month time frames. Results for monoamine oxidase inhibitors were non-significant at all timeframes and were not shown here because of small sample size (n = 85, odds ratio = 1.00, 95% confidence interval 0.64–1.56). ^bCovariates included baseline demographic covariates: age, sex, source of insurance claim, region in which medical care was received, and type of health plan. Clinical covariates were major depressive disorder diagnosis code, Charlson Comorbidity Index, presence of a comorbid anxiety disorder, and presence of a comorbid chronic non-cancer pain disorder. AD antidepressant, SNRI serotonin and norepinephrine reuptake inhibitor, TCA tricyclic antidepressant