Adherence Compliance

p Concordance:
Difficulties following medical advice

Alex J Mitchell

Ack. Dr Shoka, Dr Shanka, Dr Selmes

 “Adherence”

The extent to which the patients

behaviour coincide with the clinical
prescription/advice [ Haynes et al 1979 ].

Whatt if medical
Wh di l advice
d i iis wrong,
inadequate or missing?

Sometimes, does the patient know best?

 At Risk
Population

Does not attend / delays asymptomatic screening (if offered)

Symptoms

Dela s or does not seek help (where available)

Delays

Adherence and attendance

Diagnosis
are linked
R l
Reluctant to accept di
diagnosis
i (if told)

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

Types of Medication difficulty
Ladder of Discontinuation

Full discontinuation
Is unmonitored

Full Discontinuation
4

Trial discontinuation
Is harmless
T i l Discontinuation
Trial Di ti ti
3

Missing odd doses has

no adverse effects

Partial non-adherence
2

Benefits are unclear

Or hazards are clear

Thoughts
g of stopping
pp g
1

Medication is costly
or a hassle or linked
with stigma

0 Concordant
 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
g some Medication As Prescribed with Issues

Stopped taking medication against medical advice

10%
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
Overview
Medication Course Started Initial Treatment
N
Refusal
Y

Course interrupted

Discontinuation Missed Doses Extra Doses

Conversion to discontinuation
Full
u non-adherence
o ad e e ce Partial
a t a non-adherence
o ad e e ce
 Medication Course Started Initial Treatment
N
Refusal
Y

Course interrupted

Discontinuation Missed Doses Extra Doses

Conversion to discontinuation
Full non-adherence Partial non-adherence

P ti t wished
Patient i h d tto stop
t ttaking
ki medication?
di ti ? P ti t wished
Patient i h d tto adjust
dj t medication
di ti d
dose?
?

Y Y
N N

intentional Non intentional Intentional Non-Intentional

External Internal External Internal

Explanation
 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
 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
Examples of Medication difficulty
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.
Compliance: Hypertension

50% 44%

40%
Very Regular
30% 25% Regular
20%
20% Irregular
Forgetful
10%
2%
0%

Mallion et al, J Hypertension, 1998

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.

Medication Problems in Mental Health
 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
 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

Days
s
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
Partial compliance increases with time
Compliant

80
70
75%
of Patients Partially C

60
50
40 Up
p to 25% 50%
30
20
10
%o

0
7-10 Days* 1 Year † 2 Years †

Time From Discharge

Keith & Kane. J Clin Psychiatry 64:11;
2003
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
non-adherence
adherence
Data shown are mean and range
Cramer & Rosenheck. Psychiatr Serv 1998;49:196–201
Predicting Medication difficulty
Why Do Patients Have Difficulty?

„ With medication?

„ With appointments?
i t t ?
Predictors of Difficulty with Medication

„ Medication not working (efficacy)

„ Medication harming (side effects)
„ Medication
M di ti stigma
ti
„ Medication costs
„ Medication availability
„ Medication has helped (now not needed)
Predictors of Difficulty with Appointments?

„ Clinician not helping (efficacy)

„ Clinician harming (criticism/hostile)
„ Appointment
A i t t stigma
ti
„ Appointment travel (costs)
„ Appointment availability
„ Clinician has helped (now not needed)
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
F
Feared
d adverse
d events
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
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.
services British Journal of Psychiatry
Psychiatry, 181,
181
33 –338.
Measuring Medication difficulty
Measurement of adherence

INDIRECT
Clinicians enquiry
Patient or relative report

DIRECT
Measurement of the medication
Measurement of a biological marker
Different Ratings
Ratings, Different Results

Two separate studies found that both patients* and clinicians†

overestimate compliance

Rated as Compliant
of Patients

100 94.7

80 67.5
60
Perrcentage o

38.1
40
20 10.3
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.
Consequences of Medication Difficulty
Poor Compliance Affects Rehospitalisation
Rates
Percentage of patients with a psychiatric admission
40

35

30

25

20
P
Percent
t 15

10

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.

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
I t
Intermittent
itt t therapy
th
15
Pietzcker, et al.
35
20
S h l et al.
Schooler, l
32

0 10 20 30 40 50 60
Rates of Relapse (%)
Kane et al, 1996. N Engl J Med;334:34-41.
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

Helping with Medication difficulty
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’tt force medication as “one

Don one size fits all”
all
„ 2 Strategy-specific
Strategy specific interventions
Adjust medication timing and dosage for least
intrusion
Minimise adverse effects
Maximise effectiveness
Provide support, encouragement and follow-
up
„ 3 Reminders
Consider adherence aids such as pill boxes
and alarms
Consider reminders via mail, email or
telephone
p
Home visits, family support, encouragment
„ 4 Evaluating
g adherence
Ask about problems with medication
Ask specifically
p y about missed doses
Ask about thoughts of discontinuation
With the patient’s consent, consider direct
methods: pill counting, measuring serum

Liaise with GP & pharmacists re prescriptions

Off alternatives
Offer lt ti
Extras
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.
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

Oral medication Tips

[ Churchill et al] proposed the following

i
improvement t strategies
t t i ;
Keeping the regime simple.
Providing explicit written information
information.
Involving patients in decision making.
Encourageg p patient pparticipation
p in their own care.
Implementing drug regimes gradually.
Tailoring to daily rituals.
Providing warm positive feedback.
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
p communication between the
therapist and the patient.
Contd - 2

Further interventions studied include ;

Providing more information [ both written and oral
material and programmed learning ].
Compliance therapy.
Manual tele follow up.
S
Special
i l reminder
i d pill
ill packing.
ki
Appointment and prescription refill reminders.
L
Leverage and
d rewards.
d
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
d i i making.
decision ki
Conclusion

In a systematic review [ McDonald et al 2005 ] of

RCT off interventions
RCTs i t ti to
t assist
i t patient
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
closelyy byy familyy oriented therapies
p . The
education oriented therapies on their own were
generally unsuccessful in improving the
adherence.
adherence
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.