The document discusses medication adherence in the elderly. It describes a case of a 68-year-old man hospitalized for depression who was admitted to the ICU due to suspected digoxin intoxication from non-adherence. The document then summarizes research showing that medication non-adherence is a major driver of increased healthcare costs and hospital admissions. It discusses the three phases of adherence - initiation, execution, and persistence - and challenges in measuring execution.

1. Drug exposure and adherence in the elderly March 16 th 2010 Dr. E.R. Heerdink

2. Case Male, 68, hospitalized for serious depression with psychotic symptoms History of psychotic depression, atrial fibrillation, myocardial infarction (2002), arthritis digoxin: 0.25 mg od, acenocoumarol nortriptyline 25 mg qid, sotalol 40 mg bid amiodarone 200 mg od, enalapril 10 mg od furosemide 40 mg bid, oxazepam 10 mg tid methotrexate 7.5 mg/week, olanzapine 2.5 mg od

3. Case 2 weeks after admission, acute transfer to ICU due to suspected digoxin intoxication Digoxin: 3.6 microg/l (was: 2.5) Nortryptiline: 250 microg/l (was:84) INR: 8.5 (was: 1.5) Non-adherence -> “hospital induced intoxication”

4. Source: Manhattan Research 2004 data Disease Prevalence Reported rate of non-compliance

5. Medication non-adherence drives up healthcare costs Failure to take medication as prescribed: Causes 10% of total hospital admissions Causes 33% of CHF hospital admissions Causes 75% of Schizophrenia admissions Causes 68% of NNRTI resistant/mutated HIV virus Results in $100 billion/year in unnecessary hospital costs Causes 22% of nursing home admissions Costs the U.S. economy $300 billion/year (N Engl. J Med 8/4/05, National Pharmaceutical Council, Archives of Internal Medicine, NCPIE, American Public Health Association, AIDS 2006 20:223-232 )

6. Rebound effects When the compensating effect fades more slowly than the pharmacological effect Benzodiazepines SSRIs

7. Meijer et al Br J Psychiatry 2001

8. Rebound effects When the compensating effect fades more slowly than the pharmacological effect Benzodiazepines SSRIs Repeated first-dose effects Toxicity in first dose of a medication antihypertensives

9. “ Adherence <50%”

16. Infobesity

17. Review of statin adherence studies

20. initiation discontinuation EXECUTION of the drug regimen Three phases in adherence: Persistence (days) dichotomous dichotomous continuous

21. Initiation 10% of all prescriptions is never filled (NIVEL 2000) 30% of all antidepressant users do not fill a second precription (Van Geffen et al 2007)

22. Initiation phase 965 patients with a first prescription for a treatment with an antidepressant: 4.2% (42) do not pick up the antidepressant 23.7% (229) picks up only 1 prescription

23. Characteristics of non-starters Van Geffen et al Br J Gen Pract (2009) OR * 95% CI Non-specific indication 2.67 1.82-3.91 Non-western immigrants 4.80 2.05-11.3 >60 years of age 1.81 1.18-2.78 Precollege education level 1.40 0.83-2.36 Poor/moderate self-rated health 1.11 0.76-1.63 Paroxetine 0.78 0.53-1.13

24. Reasons for not starting therapy 57 patients with a single prescription 17 non-starters (29,8%) Fear of side effects (8) Aversion towards medication use (3) Pregnancy (2) Feeling better (2) Fear of addiction (1) Practical reasons (1) 40 (70,2%) stopped within 14 days Side effect (25) Aversion towards medication use (7) Feeling better (6) Medication ineffective (1) disagree with diagnosis (1) Ann Pharmacother 2008; 42:218-25

25. initiation discontinuation EXECUTION of the drug regimen Three phases in adherence: Persistence (days) dichotomous dichotomous continuous

26. Separate quality of execution and persistence

27. Ann Pharmacother 2006

29.  time Adherence rate = 80% time Adherence rate = 80%

30. Returned medications 4.8 % of all prescriptions are returned to the pharmacy 2 weeks 51 pharmacies Prescriptions Different drugs Dosing units 6,217 9,879 375,859

32. Perfect refill patterns  perfect adherence Erratic refill patterns  non-adherence

33. Separate quality of execution and persistence Quality of execution influences persistence

34. Wijk BLG van, Klungel OH, Heerdink ER, Boer A de Initial non-compliance with antihypertensive monotherapy is followed by complete discontinuation of antihypertensive therapy “ Poor refill compliance in first 90 days determines persistence” Pharmacoepidemiology and Drug Safety (2008)

35. time Discontinuation is often preceded by a period of dwindling execution

36. Separate quality of execution and persistence Quality of execution influences persistence Intervals between dosing determine consequences of poor execution

37. Vrijens/Urquhart Basic Clin Pharmacol Toxicol 2005

38. We can measure quality of execution to predict discontinuation to assess the effect of timing errors

39. initiation discontinuation EXECUTION of the drug regimen Three phases in adherence: Persistence (days) dichotomous dichotomous continuous

40. Beyond databases

41. Accepting Ambivalent Indifferent Skeptical Necessity Concerns High High Low Low Menckeberg et al 2008

42. Medication adherence is an important problem, especially in the elderly Initiation. Execution. Persistence Databases are great to assess persistence. Execution, not so much.

43. email: e.r.heerdink@uu.nl slides: slideshare.net/robheerdink twitter: @robheerdink