Compliance Therapy in Severe

Mental Illness

Prof Anthony David

Institute of Psychiatry,

King‟s College London, & Maudsley Hospital London UK, SE5 8AF

anthony.david@kcl.ac.uk

Adherence in general clinical practice is poor

Cramer & Rosenheck. Psychiatr Serv 1998;49:196–201

Adherence (%)

Wide range of estimates across studies may reflect

difficulty of assessing covert non-adherence

0 20 40 60 80 100

Antipsychotics

(3–24 months)

(24 studies)

Antidepressants

(1.5–12 months)

(10 studies)

Non-psychiatric

(0.25–10 months)

(12 studies)

Data shown are mean and range

Relapse rates of multi-episode antipsychotic-responsive patients*

Pro

po

rtio

n o

f p

ati

en

ts

su

rviv

ing

wit

ho

ut

rela

pse (

%) 100

80

60

40

20

0

0 6 12 18 24

Best case

Real world

Time after discharge (months) *Assumes constant optimal antipsychotic dose relapse rate of 3.5% per month, constant medication

non-adherence rate of 7.6% per month, and constant non-adherence relapse rate of 11% per month

Weiden PJ, Olfson M. Schizophr Bull 1995;21:419–27

Ability to re-label

symptomsCompliance

Awareness of

illness

The 3 Components of Insight

David AS. Br J Psychiatry. 1990;156:798-808.

Relapse in 1st episode patients over

1 year: according to compliance

0

5

10

15

20

25

30

35

Compliant Non-compliant

Relapse

Well

Novak-Grubic & Tavcar P. Eur Psychiatry 2002;17:148-54

Predictors of non-compliance:

First-episode schizophrenia

0

5

10

15

20

25

30

Poor insight Positive

symptoms

Diagnosis EPS, length of

illness, social

class etc

% v

ari

an

ce e

xp

lain

ed

Novak-Grubic & Tavcar P. Eur Psychiatry 2002;17:148-54

Risk Factors for Nonadherence in Schizophrenia

Insight/ Attitude toward medication

Poor alliance with therapist/ Less OP contact

Poor aftercare environment

Substance abuse

Previous nonadherence

Duration of symptoms

Cognitive impairment

Regimen complexity /Route

Family involvement

Symptom severity

Mood symptoms

Dosage

Age/ Gender/ Ethnicity/ Education level

Consistently associated with

adherence

Not Consistently assoc. with

adherence/inadequate data

Lacro, et al. J Clin Psychiat. 2002;63:892-909.

Concordance model Compliance model

From Compliance to Concordance

Adapted from R. Gray et al, 2004

Three phases of CT:

1. Eliciting the patient‟s stance towards

treatment;

2. Exploration of ambivalence;

3. Working towards treatment

maintenance.

RCT of Compliance Therapy Effect on Insight

70

60

50

40

30

20

10

0 Pre- 0 6 12 18 therapy

Compliance therapy

Non-specific counseling controls

Time Post-therapy (Months)

Insig

ht (S

AI-

E %

)

Kemp R, et al. Br J Psychiatry. 1998;172:413–419.

Effect of „Compliance Therapy‟ versus

non-specific counselling on adherence

1.0

0.8

0.6

0.4

0.2

0

0 100 200 300 400 500 600 Time to re-admission (days)

Re-a

dm

issio

n

Adherence (compliance) therapy

Non-specific counselling controls

Kemp R et al. Br J Psychiatry 1998;172:413–9 Maudsley Hosp study – acute in-patients

Impact of compliance therapy training on

trainee psychiatrists‟ confidence in their skills

1

2

3

4

5

6

7

After BeforeVery

confident

Not

confident

Surguladze S, et al. Psychiatr Bull 2002;26:12–5

Empathise Plan care Set limits Persuade Understand Collaboration

Impact of consultants‟ views of importance of clinical skills

0

1

2

3

4

5

6

7

Authoritative advice Listening empathically

Before

After

Very

important

Not

important

Surguladze, Timms & David (2001) Psychiatric Bull

Referred by clinicians as

meeting criteria, n=1218

Total Excluded n= 809

Not IGC schizophrenia n=52

Not meeting other inclusion

criteria n=249

Refused to participate n=366

Other reasons n=142

Adherence therapy

n=204

Completed therapy

n=182

Did not complete

therapy

n=22

1 year follow-up

n=178

Not followed up

n=26

Health Education

n=205

Completed therapy

n=173

Did not complete

therapy

n=32

1 year follow-up

n=194

Not followed-up

n=11

Randomised n=409

KING'SCollege

LONDONFoundedI829

QUATRO STUDY Gray, et al (2006)

Adherence Therapy: “QUATRO”* Study

2

3

4

5

Health Education Adherence Therapy

Kem

p C

om

pli

an

ce S

cale

Before

After

*Multicentre EU study of OP maintenance Rx

Health Educ. (Control), n=171

Adherence Ther., n=156 Gray, et al (2006) Brit J Psychiat, 189:508-14

No significant effect of Adherence Therapy

QUATRO Study

• No significant effect of Adherence Therapy

– ?Subgroups may be identified who benefit more

– Baseline levels of adherence were fair -

?ceiling effect

– Patients enrolling for clinical trial are „compliant‟

– Intervention may have more effect post acute

relapse (cf Kemp et al) rather than in maintenance

phase

Factors that affect treatment adherence

Increase

• Acceptance of illness

• Perception of severity/ susceptibility

• Level of support

• Family stability

• Positive therapeutic alliance

• Formulation/delivery

Decrease

• Side effects

• Poor symptom control

• Complex regimen

• Substance abuse

• Impaired judgement

• Poor doctor–patient relationship

• Poor communication

Depot conventionals versus oral conventionals: meta-analysis of RCTs

Relapse rates: summary

Adams CE, et al. Br J Psychiatry 2001;179:290–9

To

tal n

=846 (

RR

0.9

6)

(0.8

0–1.1

4)

36%

35%

Depot (n=146/420)

Oral (n=153/428)

0 20 40 60 80 100

Rates of relapse (%)

46%

19%

Depot versus oral conventionals: meta-analysis of RCTs

Adams CE et al. Br J Psychiatry 2001;179:290–9

Global improvement

Patients (%)

0 20 40 60 80 100

To

tal n

=127 R

R 0

.68

(CI=

0.5

4–0.8

6)

RR = risk ratio

CI = confidence interval

Oral (n=12/62)

Depot (n=30/65)

Risk of Rehospitalisation by

medication – best results with depot*

Tiihonen et al (2006) BMJ 333: 224-230

*Adjusted for sex, year, length of follow-up,

duration of 1st admission.

Depot or oral? Patient preference according to current formulation

0

10

20

30

40

50

60

70

80

90

100

%

On Depot (n=76) On Oral (n=146)

Prefers depot

Prefers oral

No preference

Patel et al (2009) Journal of Psychopharmacol, 23: 789–796

• More CMHT patients on depot

felt people try to force them to

take medication

• 30% vs 2%, p<0.001

People try to force them

depot oral0

20

40

60

80

100

%

• More CMHT patients on oral

felt no-one tried to force them

to take medication

• 90% vs 65%, p=0.01

No-one forces them

depot oral0

20

40

60

80

100

%

Coercion: depot vs oral

Patel, et al. (2009) J Psychophamacol in press.

CTOs: How do we use them?

Conditions

-Attendance at Appts

-Medication adherence

-Residence specified

N (%)

178 (91.3)

177 (90.8)

103 (52.8)

Antipsychotics @ initiation

-Oral

-Depots

-Clozapine

46 (23.7)

105 (53.8)

23 (11.8)

(n=195) Patel et al (2011) Ther Adv Psychopharmacol 1:37-45

FIAT: Financial

incentives to

improve adherence

to antipsychotic

maintenance

medication in non-

adherent patients

- a cluster randomised

controlled trial

BMC Psychiatry Study protocol

Stefan Priebe, Alexandra Burton, Deborah Ashby, Richard Ashcroft, Tom Burns, Anthony David, Sandra Eldridge, Mike Firn, Martin Knapp and Rose McCabe.

Will be reporting this year….

http://www.biomedcentral.com/1471-244X/9/61

Trial Registration: Current controlled trials ISRCTN77769281.

Conclusions

• Partial adherence is a major problem in

medicine, but especially schizophrenia; it is the

major cause of relapse

• Pharmacological and Psycho-social approaches

may improve adherence and insight:

• CBT Approaches – based on collaboration

• Formulation e.g. depots (?associated with coercion)

• Compulsion

• Incentives?

On disagreements with players, the late maverick English football manager Brian Clough said: “I ask him which way he thinks it should be done, we get down to it, we talk about it for 20 minutes, and then we decide I was right”.