Predicting antidepressant persistence by

patient and prescriber characteristics:

a Belgian medical claim database study AN TAMSIN & DIONA D’HONDT

PROMOTOR: PROF. DR. FRANK DE SMET

COPROMOTOR: PROF. DR. KOEN DEMYTTENAERE

Introduction

Aim of the study

Material and methods

Results

Discussion

Conclusion

Introduction

Belgium is a leading European country in terms of antidepressant use (AD)(1)

DDD doubled the last twenty years (40 to 77 DDD / 100 residents / day)(2) despite numerous

campaigns

National (3) and international guidelines: adequate treatment =

minimum 6 months following the resolution of symptoms (after four to six weeks)

prevents relapse and recurrence

Shorter treatment duration is not uncommon / Adherence to initial AD medication

decreases over months (4–6)

Inadequate treatment has psychopathological and psychosocial consequences, decreases work productivity and quality of life (9)

Aim of the study

Analyse which characteristics of

Patients

Prescribers

may predict the duration of antidepressant (AD) therapy

Material and methods

Data extractions and analyses

R&D Department of the National Alliance of Christian Sickness Funds (CM)

Study design

Nationwide retrospective cross-sectional study

Administrative claim database of CM:

(reimbursed procedure codes)

records for reimbursed, dispensed prescriptions

sociodemographic characteristics

clinical diagnoses were not available

M & M: selection of antidepressants

Anatomical Therapeutic Chemical (ATC): all SSRIs (except for sertraline), all SNRIs (except for venlafaxine), all TCAs, bupropion, agomelatine, mianserineand mirtazapine.

Not included: venlafaxine, sertraline, trazodone, dosages too low to be therapeutically of value in the treatment of depression

ADs delivered between 01.01.2005 and 31.12.2015

Information AD:

Total amount of reimbursed and dispensed packages

Number of packages per reimbursement

Price of a reimbursement

CNK code of package

M & M: estimation length of episode

Days prescribed =

1 package = 98 days

4 dispensed packages:

01/10/2009

20/01/2010

(grace period 13 days = ok)

10/04/2010

(overlap until 15/04 = not

counted)

01/01/2013

Total amount of days = 3 x 98

= 144 days

Length of episode =

139 days

10/04/2010 + 98 days =

17/07/2010

minus

01/10/2009

Flexible doses: the lowest daily dose was used

-Grace period: 30 days-Switching between different ADs = a continuous AD consumption

Material and methods

Episode selection and exclusion

Treatment periods ongoing on 01.01.2010

Exclusion:

(Episodes of) patients who were (at start of the treatment episode):

< 18 or > 65 years

nursing home residents

unknown or offshore address

During the episode: died or changed their membership to another insurance fund (per trimester)

Episodes started before 2005

Material and methods

Patient characteristics

age

gender

unemployment and disability

major coverage allowance

hospitalization during the episode

geographical categorization

first treatment episode in the study period

Prescriber characteristics

age

gender

medical specialty

number of consultations performed by a

physician during the first year of the study

period (i.e., 2005)

number of ADs prescribed days in 2005

Material and methods

Statistical methods

Multivariate ordinary least-squares regression with clustering at prescriber’s level

was performed using the above mentioned variables.

Exclusion censored data: 1432 patients

Results

Overall

180 003 reimbursements

50% presented only one package

Median refund cost of €23.26

After estimation of LoE

Minimum 1, maximum 56, median 3 treatment episodes

Results

After selection (treatment ongoing on 01.01.2010)

96 584 treatment periods

LoE

Ranged from 13 to 3828 days

Median 341 days

Mean 608 days

50% of patients were treated with ADs for almost one year

31.57% of patients had a length of treatment episode shorter than 180 days

Patient characteristics

96 584 patients

Mean age 47 years - median age 48 years

67% female

85% first treatment episode during the 10 year study

period

Non disability, employment, major coverage,

hospitalization during episode

Center, residential

Results

Results

Characteristics of (most prevalent) prescriber

one prescriber is responsible for prescribing: 50%

14443 unique prescribers

1 to 142 patients per prescriber

psychiatrist most prevalent prescriber: 28%

70% is male

mean and median year of birth = 1959

Results

Results

Discussion

Length of episode

Median 341 days

Mean 608 days

Patients with long-term treatment are more present than patients with

a short-term treatment

15% already had an earlier treatment episodes ↔ only first time users

31,75% discontinued treatment < 6 months = similar to most other

studies

Prescriber’s intention to treat with short courses: off-label, non-mental

health indications or sub-threshold disorders and minor depressive disorders (10) shorter LoE

Discussion

Length of episode

Dispensed daily dose: surrogate of PDD ↔ DDD

Unable to check the prescribed dose

Lowest daily dose in case of flexible dosages ↔ highest daily dose

Grace period of 30 days

Shorter might imply misclassification of consecutive episodes as new episodes

Longer grace period would have overestimated 6-month persistence (11)

Discussion

Patient characteristics

Gender

Population female (67%) = other studies

Being male reduced the LoE with 20 days ↔ indifference in literature

Age

For each year a patient gets older, the LoE increased with 4 days = other studies

Hospitalization

Hospitalization expanded LoE = other study however they used another definition and did not reach statistical significance (45.7% versus 54.7%, respectively, p = 0.053) (12).

Discussion

Patient characteristics

First time treatment

First time treatment shortened LoE = other studies (13) : 1/3 first-time users did not purchase an AD <6 months following first prescription (14). Persistence rates after an initial AD dropped to 20-30% at month 6 (15,16).

Socioeconomic status

# days unemployment or disability, presence of major coverage allowance ↔ presence of unemployment and disability

major coverage allowance or unemployed < 6 months expanded LoE = more discontinuation among unemployed (14) ↔ unemployment no significant correlation (17)

LoE 68 days shorter during the first six months of disability

Discussion

Prescriber characteristics

Specialty

Psychiatrist in 28% ↔ lower in France (8.6%) (18), Netherlands (9.5%) (19), USA (15%)(4)) or higher USA 35% (20)

Psychiatrist expand LoE = other studies (4,12,17,21) except for 2 studies proof association (20,22)

Age

Younger physician larger episode ↔ two studies no association (14,22)

Gender

No association between gender and AD persistence = other studies (14,22)

Discussion

Prescriber characteristics

Shorter LoE with higher general amount of AD prescribed days of the prescriber

= Hansen et al. (14)

Positive correlation workload and the LoE ↔ Hansen et al. no statistically

significant correlation despite same definition (14)

Strengths and limitations

Strengths

First to analyze duration of AD treatment in a large population (41%)

representative for Belgian population

Medical claims databases are common used and has several advantages

Huge sample size(23)

Patients and doctors unaware information bias avoided (14)

Strengths and limitations

Limitations

Observational study : causality of the correlations reported?

Dispensing data:

underestimation of the prescription data

intention to (comply with treatment) ?

Other variables (concomitant medications, comorbid illnesses, immigration background or

educational level (47)?

Exclusion venlafaxine and sertraline

Relationship between characteristics and whether the length of this treatment period is

adequate or not is beyond the aim of this study

Future research

Studies confirming or disclaiming the suggested explanations for the

correlations found in this and other studies are needed.

Investigating the correlation between characteristics and inadequate

treatment duration:

too short(< 180 days according to guidelines)

very long LoE (e.g., 75th percentile of LoE)

target campaigns for AD use in specific subpopulations and for specific

prescribers

Conclusion

Confirmation of earlier studied associations between persistence on AD and patient/prescriber characteristics

Following factors extend the LoE

Female, older patient

AD prescribed by psychiatrist, by physician with lower prescribing behavior

Additional findings

Following factors extend the LoE

being hospitalized, low socioeconomic status

young prescribers, higher workload physician

Following factors shortened LoE

first episode

Future research

References

1. Lewer D, O’Reilly C, Mojtabai R, et al. Antidepressant use in 27 European countries: Associations with sociodemographic, cultural and economic factors. Br J Psychiatry. 2015;207(3):221–226.

2. Vansnick L. «IPhEB-Monthly» Data februari 2016. Vol. mei. 2016. 3. Declercq T, Habraken H, Van Den Ameele H, et al. Domus medica-richtlijn depressie bij volwassenen. Huisarts Nu.

2017;45(1). 4. Pomerantz J, Finkelstein S, Berndt E, et al. Prescriber intent, off-label usage, and early discontinuation of antidepressants: A

retrospective physician survey and data analysis. J Clin Psychiatry. 2004;65(3):395–404. 5. Sansone R, Sansone L. Antidepressant adherence: Are patients taking their medications? Innov Clin Neurosci. 2012;9(5–

6):41–46. 6. Keyloun K, Hansen R, Hepp Z, et al. Erratum to: Adherence and Persistence Across Antidepressant Therapeutic Classes: A

Retrospective Claims Analysis Among Insured US Patients with Major Depressive Disorder (MDD). CNS Drugs. 2017;31(6):511. 7. Osterberg L, Blaschke T, Koop C. Adherence to Medication. N Engl J Med. 2005;353:487–497. 8. Rivero-Santana A, Perestelo-Perez L, Perez-Ramos J, et al. Sociodemographic and clinical predictors of compliance with

antidepressants for depressive disorders: Systematic review of observational studies. Patient Prefer Adherence. 2013;7:151–169.

9. Keller M, Boland R. Implications of failing to achieve successful long-term maintenance treatment of recurrent unipolar major depression. Biol Psychiatry. 1998;44(5):348–360.

10. Poluzzi E, Piccinni C, Sangiorgi E, et al. Trend in SSRI-SNRI antidepressants prescription over a 6-year period and predictors of poor adherence. Eur J Clin Pharmacol. 2013;69(12):2095–2101.

11. Bushnell G, Stürmer T, White A, et al. Predicting persistence to antidepressant treatment in administrative claims data: Considering the influence of refill delays and prior persistence on other medications. J Affect Disord. 2016;196:138–147.

12. Kogut S, Quilliam B, Marcoux R, et al. Persistence with Newly Initiated Antidepressant Medication in Rhode Island Medicaid: Analysis and Insights for Promoting Patient Adherence. R I Med J (2013). 2016;99(4):28–32.

References

13. Burton C, Anderson N, Wilde K, et al. Factors associated with duration of new antidepressant treatment: Analysis of a large primary care database. Br J Gen Pract. 2012;62(595):104–112.

14. Hansen D, Vach W, Rosholm J, et al. Early discontinuation of antidepressants in general practice: Association with patient and prescriber characteristics. Fam Pract. 2004;21(6):623–629.

15. Sawada N, Uchida H, Suzuki T, et al. Persistence and compliance to antidepressant treatment in patients with depression: a chart review. BMC Psychiatry. 2009;9:38.

16. Mullins C, Shaya F, Meng F, et al. Persistence, switching, and discontinuation rates among patients receiving sertraline, paroxetine, and citalopram. Pharmacotherapy. 2005;25(5):660–667.

17. Trifirò G, Tillati S, Spina E, et al. A nationwide prospective study on prescribing pattern of antidepressant drugs in Italian primary care. Eur J Clin Pharmacol. 2013;69(2):227– 236.

18. Sanglier T, Saragoussi D, Milea D, et al. Comparing antidepressant treatment patterns in older and younger adults: A claims database analysis. J Am Geriatr Soc. 2011;59(7):1197–1205.

19. Gardarsdottir H, Egberts T, Heerdink E. The association between patient-reported drug taking and gaps and overlaps in antidepressant drug dispensing. Ann Pharmacother. 2010;44(11):1755–1761.

20. Chen S, Hansen R, Gaynes B, et al. Guideline-concordant antidepressant use among patients with major depressive disorder. Gen Hosp Psychiatry. 2010;32(4):360–367.

21. Wu C, Shau W, Chan H, et al. Persistence of antidepressant treatment for depressive disorder in Taiwan. Gen Hosp Psychiatry. 2013;35(3):279–285.

22. Ayalon L, Gross R, Yaari A, et al. Disparities in antidepressant adherence in primary care: Report from Israel. Am J Manag Care. 2011;17(9):340–347.

23. Hung C. Factors predicting adherence to antidepressant treatment. Curr Opin Psychiatry. 2014;27(5):344–349.