This is an academic talk on the evidence base behind adherence (difficulty taking) prescribed medication. I gave this as a small talk from the local NHS trust in 2007.

1. Adherence Compliance Concordance:
p
Difficulties following medical advice
Alex J Mitchell
Ack. Dr Shoka, Dr Shanka, Dr Selmes

2. “Adherence”
The extent to which the patients
behaviour coincide with the clinical
prescription/advice [ Haynes et al 1979 ].
What
Wh t if medical advice i wrong,
di l d i is
inadequate or missing?
Sometimes, does the patient know best?

3. At Risk
Population
Does not attend / delays asymptomatic screening (if offered)
Symptoms
Delays
Dela s or does not seek help (where available)
Adherence and attendance
Diagnosis
are linked
R l
Reluctant to accept di
diagnosis (if told)
i
Early
Treatment
Reluctant to start treatment (if offered)
Follow Up
Does not attend further appointments (if offered)
Continuation
Treatment
Does not follow course as prescribed

4. Types of Medication difficulty

5. Ladder of Discontinuation
Full discontinuation
Is unmonitored
Full Discontinuation
4
Trial discontinuation
Is harmless
Trial Di
T i l Discontinuation
ti ti
3
Missing odd doses has
no adverse effects
Partial non-adherence
2
Benefits are unclear
Or hazards are clear
Thoughts of stopping
g pp g
1
Medication is costly
or a hassle or linked
with stigma
0 Concordant

6. Poor Compliance is Normal (Barber et al)
N Barber et al Patients’ problems with new medication for chronic Patients’ conditions.
Qual Saf Health Care 2004;13:172–175.
Taking All Medication As Prescribed
& Problem Free & with sufficient information 10%
Taking some Medication As Prescribed & Problem Free
Taking some Medication As Prescribed with Issues
g
Stopped taking medication against medical advice
10%

7. Types of Adherence Problems
Initial vs follow up
Refusal vs discontinuation
Non-attendance vs drop out
Partial vs Full vs Over
Partial attender, takes some medication,
takes too much medication

8. Overview
Medication Course Started Initial Treatment
N
Refusal
Y
Course interrupted
Discontinuation Missed Doses Extra Doses
Conversion to discontinuation
Full non-adherence
u o ad e e ce Partial non-adherence
a t a o ad e e ce

9. Medication Course Started Initial Treatment
N
Refusal
Y
Course interrupted
Discontinuation Missed Doses Extra Doses
Conversion to discontinuation
Full non-adherence Partial non-adherence
Patient i h d to t
P ti t wished t stop t ki
taking medication?
di ti ? P ti t wished t adjust medication d
Patient i h d to dj t di ti dose?
?
Y Y
N N
intentional Non intentional Intentional Non-Intentional
External Internal External Internal
Explanation

10. Medication Course Started Initial Treatment
N
Refusal
Y
Course interrupted
Discontinuation Missed Doses Extra Doses
Full non-adherence Partial non-adherence
Patient wished to adjust medication dose?
Patient wished to stop taking medication?
Y Y
N N
intentional Non intentional Intentional Non-Intentional
With medical advice?* External Internal External Internal
With medical advice?*
Barrier Lapse or Slip Barrier Lapse or Slip
Y
N Y N
Collaborative Self Directed
Self-Directed Collaborative Self Directed
Self-Directed
Based on adequate information? Based on adequate information?
N Y N Y
High Risk of Harm Low Risk of Harm High Risk of Harm Low Risk of Harm
* Advice implies consultation and discussion of risk and benefits not necessary sanction to act

11. Medication Course Started Initial Treatment
N
Refusal
Y
Course interrupted
Discontinuation Missed Doses Extra Doses
Conversion to discontinuation
Full non-adherence Partial non-adherence
Patient wished to adjust medication dose?
Patient wished to stop taking medication?
Y Y
N N
intentional Non intentional Intentional Non-Intentional
With medical advice?* External Internal External Internal
With medical advice?*
Barrier Lapse or Slip Barrier Lapse or Slip
Y
N Y N
Collaborative Self Directed
Self-Directed Collaborative Self Directed
Self-Directed
Based on adequate information? Based on adequate information?
N Y N Y
High Risk of Harm Low Risk of Harm High Risk of Harm Low Risk of Harm
* Advice implies consultation and discussion of risk and benefits not necessary sanction to act

12. Examples of Medication difficulty

13. Compliance: Rheumatoid Arthritis
45
40.3
40 3
40 35.7
35
Consistently
30 Compliant
23.8
25 Consistently Non-
%
20 compliant
15 Other - ?partial
compliance
10
5
0
•556 pts with RA followed for 3 years
•Compliance assessed annually by interview
Viller F et al. J Rheumatol. 1999;26:2114-2122.

14. Compliance: Hypertension
50% 44%
40%
Very Regular
30% 25% Regular
20%
20% Irregular
Forgetful
10%
2%
0%
Mallion et al, J Hypertension, 1998

15. The problem of poor compliance
Patients not 90
adhering by 80
disease area
Arthritis
(%)
55 Epilepsy
Hypertension
40 40 Diabetes
35
Asthma
Contraception
p
Whitney HAK et al. Annals of Pharmacotherapy 1993.

16. Medication Problems in Mental Health

17. Percentage of Patients Discontinuing Antipsychotics in
18month CATIE Trial
80
74
70
60
50
40
29.9
30
23.7
20
14.9
14 9
10 5.5
0
Other Intolerability Lack of Efficacy Patient Decision Total
Discontinuations

18. Compliance challenges affect almost ALL
patients*
Continuous Medication
ANY Days Without Medication Mean Number of Days
Without Medication
100 5.2% 7.1%
94.8% 350
92.9%
80 300
250
60
nts
s
Days
200
Patien
(%))
40 150 110.2
125.0
100
20
50
0 0
Atypical Conventional Atypical Conventional
n = 349 n = 326 n = 349 n = 326
Mahmoud et al, 2004. Clin Drug
Invest:24(5):1

19. Partial compliance increases with time
% of Patients Partially Compliant
80
70
75%
C
60
50
40 Up to 25%
p 50%
30
20
10
o
0
7-10 Days* 1 Year † 2 Years †
Time From Discharge
Keith & Kane. J Clin Psychiatry 64:11;
2003

20. Adherence in general clinical practice is poor
Antipsychotics
(3–24 months)
(24 studies)
Antidepressants
p
(1.5–12 months)
(10 studies)
Non-psychiatric
(0.25–10 months)
(12 studies)
0 20 40 60 80 100
Adherence (%)
Wide range of estimates across studies may reflect
difficulty of assessing covert non adherence
non-adherence
Data shown are mean and range
Cramer & Rosenheck. Psychiatr Serv 1998;49:196–201

21. Predicting Medication difficulty

22. Why Do Patients Have Difficulty?
With medication?
With appointments?
i t t ?

23. Predictors of Difficulty with Medication
Medication not working (efficacy)
Medication harming (side effects)
M di ti stigma
Medication ti
Medication costs
Medication availability
Medication has helped (now not needed)

24. Predictors of Difficulty with Appointments?
Clinician not helping (efficacy)
Clinician harming (criticism/hostile)
Appointment stigma
A i t t ti
Appointment travel (costs)
Appointment availability
Clinician has helped (now not needed)

25. Perceived Benefits of Care Perceived Costs of Care Barriers to Care Doctor-Patient Factors
Lack of transportation Therapeutic alliance
Previous bad experiences
Reduced symptoms
Financial inequalities Perceived helpfulness
Feared adverse events
F d d t
Prevention of complications
Infrequent appointments Communication style
Financial costs
Enhanced therapeutic relationship
Inconvenient appointments Adequacy of explanation
Dislike of medical model
Improved Health Related QoL
Inconvenience
Stigmatization Adequacy of monitoring
Self-Medication Behaviour Attendance Behaviour
Ideal Concordance Disengagement (drop-out)
Good Concordance Low Attendance
Partial Concordance Partial Attendance
Desire to continue
Low Concordance medical care Good Attendance
Desire to stop
+ Encouragement
Discontinuation medical care Ideal Attendance
+ Distracters
Cues to Act
Illness Factors
Non-intentional Intentional Reminders
Insight into current symptoms
Flexible booking / Open access
Perceived risk of future decline May Not be Disclosed Likely to be Disclosed
Delivery or collection of medication
Previous treatment responsiveness Reasons incoherent Reasons coherent
Encouragement / support by others
Likelihood of treatment benefits No alternatives Alternatives discussed
considered

26. Adherence and Satisfaction
Audience: what is the relationship?
Higher rated treatment success => drop-out
drop out
Low rated clinician => drop-out
Rossi, A., Amaddeo, F., Bisoffi, G., et al (2002) Dropping out of
care: inappropriate terminations of contact with community based
psychiatric services. British Journal of Psychiatry 181
services Psychiatry, 181,
33 –338.

27. Measuring Medication difficulty

28. Measurement of adherence
INDIRECT
Clinicians enquiry
Patient or relative report
DIRECT
Measurement of the medication
Measurement of a biological marker

30. Different Ratings Different Results
Ratings,
Two separate studies found that both patients* and clinicians†
overestimate compliance
Rated as Compliant
rcentage of Patients
100 94.7
80 67.5
60
o
38.1
40
20 10.3
Per
0
Pill Count Patient MEMS Cap Clinician
*Criterion: ”took all pills.”
†Criteria:
>70% of days (MEMS cap); score >4 on clinician rating scale.
*Lam YWF et al. Poster presented at: Biennial Meeting of ICOSR; March 29 – April 2, 2003;
Colorado Springs, Colorado.
†Byerly M et al. Poster presented at: Annual Meeting of APA; May 17-22, 2003; San Francisco, California.

31. Consequences of Medication Difficulty

32. Poor Compliance Affects Rehospitalisation
Rates
Percentage of patients with a psychiatric admission
40
35
30
25
20
P
Percent
t 15
10
5
0
10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 110% 120% 130%
Medication Possession Ratio
Valenstein M, et al. Medical Care. 2002;40:630-639.

33. Continuous vs intermittent maintenance: 1
year relapse rates
33
Carpenter, et al.
55
10
Herz, et al.
29
Continuous therapy
7
Jolley, et al.
30
Intermittent therapy
I t itt t th
15
Pietzcker, et al.
35
20
Schooler,
S h l et al.
l
32
0 10 20 30 40 50 60
Rates of Relapse (%)
Kane et al, 1996. N Engl J Med;334:34-41.

34. Relapse in 1st episode patients over
1 year: according to compliance
35
30
25
20 Relapse
15 Well
10
5
0
Compliant Non-compliant
Novak-Grubic & Tavcar P. Eur Psychiatry 2002;17:148-54

35. Helping with Medication difficulty

36. 4 Steps
1 Basic communication
Establish a therapeutic relationship and trust
Identify the patient’s concerns
Take into account the patient’s preferences
Explain the benefits and hazards of treatment options
Involve patients in decisions
Don t
Don’t force medication as “one size fits all”
one all

37. 2 Strategy-specific interventions
Strategy specific
Adjust medication timing and dosage for least
intrusion
Minimise adverse effects
Maximise effectiveness
Provide support, encouragement and follow-
up

38. 3 Reminders
Consider adherence aids such as pill boxes
and alarms
Consider reminders via mail, email or
telephone
p
Home visits, family support, encouragment

39. 4 Evaluating adherence
g
Ask about problems with medication
Ask specifically about missed doses
p y
Ask about thoughts of discontinuation
With the patient’s consent, consider direct
methods: pill counting, measuring serum
Liaise with GP & pharmacists re prescriptions
Offer lt
Off alternatives
ti

40. Extras

41. Potential to Improve Relapse Rates
With Depot vs Oral Antipsychotics
Difference in
Relapse Rates
Number of Study Relapsed (%) (oral minus
Study subjects duration Oral Depot depot) (%)
Crawford and Forest
29 40 weeks
k 27 0 27
(1974)
del Guidice et al (1975) 82 1 year 91 43
48
Rifkin et al (1977) 51 1 year 11 9 2
Falloon et al (1978) 41 1 year 24 40 -16
Hogarty et al (1979) 105 2 years 65 40 24
Schooler et al (1979) 214 1 year 33 24 9
— +
Mantel-Haenszel: P < 0.0002.
Davis JM et al. Drugs. 1994;47:741-773.

42. Degree of difficulty to produce adherence sufficient
for therapeutic effect
Weight Reduction
Schizophrenia
Exercise
Flossing
g
Hypertension
Diabetes (insulin depot)
Diabetes (oral)
Depression
Rheumatoid Arthritis
Asthma
Strep Throat
Birth Control Pills
Headache
20 40 60 80 100
Easy Difficult
Keith & Kane J Clin Psychiatry, 2003; 64: 1308-1315

43. Oral medication Tips
[ Churchill et al] proposed the following
improvement strategies ;
i t t t i
Keeping the regime simple.
Providing explicit written information
information.
Involving patients in decision making.
Encourage p
g patient p participation in their own care.
p
Implementing drug regimes gradually.
Tailoring to daily rituals.
Providing warm positive feedback.

44. Interventions to improve adherence
Osterberg et al 2005 grouped intervention in
to four categories;
Patient education
education.
Improved dosing schedules of medication.
Increasing clinic hours.
Improved communication between the
p
therapist and the patient.

45. Contd - 2
Further interventions studied include ;
Providing more information [ both written and oral
material and programmed learning ].
Compliance therapy.
Manual tele follow up.
Special reminder pill packing.
S i l i d ill ki
Appointment and prescription refill reminders.
Leverage and rewards.
L d d

46. Contd - 6
Other interventions ;
In a systematic review [ Bennett & Glaziou 2003 ]
which included 26 RCTs of computer generated
medication reminders or feedbacks provided to
the pts / health care providers concluded that the
reminders are effective than feedback in
improving adherence
adherence.
Mugford et al showed that information was most
effective when presented close to the time of
decision
d i i making.ki

47. Conclusion
In a systematic review [ McDonald et al 2005 ] of
RCTs f i t
RCT of interventions to assist patient
ti t i t ti t
adherence to meds concluded in psychiatric
disorders the overall combination interventions
and compliance counselling for pts appeared to
be effective for improving adherence followed
closely by family oriented therapies . The
y y y p
education oriented therapies on their own were
generally unsuccessful in improving the
adherence.
adherence

48. Conclusion
Evidence for any single intervention to
improve adherence is weak however a
combination of educational, cognitive and
behavioural measures [ collaborative care
] have shown to improve the adherence to
medication with the psychiatric patients.
Further research is needed.