The Wheel Of Compliance

Dr Ahmed Shoka Consultant Psychiatrist

Schizophrenia
Strikes one in a hundred And affects many more.

Conformity
Leon Mann, it meansyielding to group pressures.It has three distinct areas of meaning: 1- Behaviour 2-Attitudes 3- Personality traits 3 sub-types :1- Normative; comprises compliance(seeming to agree) and true conformity(actually agreeing), 2- Informational; copying a behaviour or attitude in order to be accepted as a member, 3-Ingratiational; do what ever the other will approve in order to gain acceptance, i.e. fear of being rejected.

Obedience
It is a special form of compliance It is compliance where we generally do not want to comply It also implies that someone is in power or authority over us giving us specific orders, requests or suggestions that require us to respond in some way. It is like conformity, may be beneficial or destructive.

Compliance
Definition: The extent to which a persons behaviour (in terms of taking medications, following diets or executing lifestyle changes) coincides with medical or health advice Terminology: Compliance Alliance Fidelity Adherence Concordance

Partial Compliance
= not taking medication as prescribed

- missing doses - drug holidays - lower dose vs Rx -

Spectrum of Compliance
Non-satisfactory compliance
Noncompliance

Acceptable compliance Partial compliance

0%

Adherence to prescribed treatment

100%

Defining levels of compliance

Level of compliance
Compliant Partially compliant Noncompliant

Average of experts preferred definitions

Patient misses < 25% of medication Patient misses 25%65% of medication Patient misses > 65% of medication

Kane et al, 2003. J Clin Psychiatry; 64, Suppl 12 .

Up to 80% of patients with psychotic disorders fail to comply with their medication regimen at some point during the course of their treatment.

Adherence in general clinical practice is poor

Antipsychotics (324 months) (24 studies)
Antidepressants (1.512 months) (10 studies) Non-psychiatric (0.2510 months) (12 studies) 0 20 40 60 Adherence (%) 80 100

Wide range of estimates across studies may reflect difficulty of assessing covert non-adherence
Data shown are mean and range Cramer & Rosenheck. Psychiatr Serv 1998;49:196201

Compliance in Chronic Medical Illnesses

Rates of compliance were only 25% for patients with diabetes 67% for those with rheumatoid arthritis 53% for those with hypertension

In schizophrenia, it is estimated that up to 50% of out-patients and 20% of in-patients are not compliant with prescribed medication.

Reported extent of compliance

Level of compliance
Compliant (misses <20% of medication) Partially compliant (misses 20-80% of medication) Noncompliant (misses >80% of medication)

Experts estimate of compliance levels in their patients

43% 38% 19%

Kane et al, 2003. J Clin Psychiatry; 64, Suppl 12 .

Adherence is best understood in dimensional rather than categorical terms.

Most Schizophrenia Patients Experience Interruptions in Therapy

Poor insight into illness Reminder of illness Forget (refuse?) to take medication Side effects Perceived poor quality of life (QoL) Loss of motivation Lack of psycho-education

Noncompliant

Compliant

Partially compliant

Oehl. Acta Psychiatr Scand. 2000;102(suppl 407):83-86.

Several factors influence compliance of patient with schizophrenia

The person
Age/gender Social status Cultural & family values Experiences of illness & treatment Support network & milieu Personality Insight/denial Intelligence Views of illness/role of med.

The treatment
Therapeutic alliance Treatment setting/inform. Effectiveness

Complexity/supervision
Side effects/satisfaction(EPS, NIDS, weight..) Stigma

The illness The Physician

Beliefs / recommendations Dosing, follow up Education, attitude Substance use Delusional beliefs (paran., grand.,) Positive aspects of illness experience

Depression / anxiety / cogn. imp.

Duration

Compliance is to gained by clinician.

Degree of difficulty to produce adherence sufficient for therapeutic effect

Weight Reduction Schizophrenia Exercise Flossing Hypertension Diabetes (insulin depot) Diabetes (oral) Depression Rheumatoid Arthritis Asthma Strep Throat Birth Control Pills Headache 20 Easy 40 60 80 100 Difficult

Keith & Kane J Clin Psychiatry, 2003; 64: 1308-1315

Partial compliance in schizophrenia begins early and prevalence increases over time
% of Patients Partially Compliant

80 70 60 50 40 30 20 10 0 7-10 Days* 1 Year

75%
Up to 25%

50%

2 Years

Time From Discharge

Keith & Kane. J Clin Psychiatry 64:11; 2003

Compliance challenges affect almost ALL patients*

Continuous Medication ANY Days Without Medication

100 80

Mean Number of Days Without Medication

350 300 250

5.2% 94.8%

7.1% 92.9%

Patients (%)

Days

60 40 20 0

200 150 100 50 0

110.2 125.0

Atypical n = 349

Conventional n = 326

Atypical n = 349

Conventional n = 326

Mahmoud et al, 2004. Clin Drug Invest:24(5):1

Medication Compliance: Atypical vs Typical

100

Prescription Refill Rate

80

P = 0.05

P = NS

% Adherent Fills 40
20 0

60

57.4

49.9

54.9

50.1

Atypical

Typical

Atypical

Typical

6 months
Prescription refill rate = (# adherent fills / total # of fills ) x 100

12 months
Dolder et al. Am J Psychiatry. 2002;159:103-108.

Positive effects of atypicals:the evidence

Symptom
Ve+ symptoms Ve- symptoms Affective symptoms Aggression Cognition

Quality of evidence
Definitive Definitive,primary Ve-?? Strong & Growing Emerging Strong & Growing

Measurement of (non)-compliance
Simple methods are not accurate and accurate methods are not simple Simple
Anamnesis Pill counts Prescription counts

Not simple
Drug/metabolite concentration MEMS (medication event monitoring system)

Accurate assessment of compliance is difficult for patients with schizophrenia and clinicians
Two separate studies found that both patients* and clinicians overestimate compliance
Percentage of Patients Rated as Compliant

100 80 60 40 20 0 Pill Count Patient

Criteria:

94.7

67.5 38.1 10.3

MEMS Cap

Clinician

*Criterion: took all pills. >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.

Compliance

The Compliance Cycle

Disclosure of diagnosis Psycho-education Create therapeutic alliance to ensure cooperation Proper community follow up Adjust and negotiate Relapse prevention and crisis intervention CT; once non compliant is not always non compliant

Compliance is difficult to measure accurately

Compliance measures are not readily utilized and/or available to most clinicians
Pill counts/blood tests
Unreliable (pill dumping, white coat compliance) Cumbersome, inconvenient

Physicians rely on patient reports

Patients overestimate compliance/do not comply for numerous reasons

Lack of insight Irregular routines Side effects Substance abuse Symptom exacerbation

Predictors of non-compliance
% variance explained

30 25 20 15 10 5 0 Poor insight Positive symptoms Diagnosis EPS, length of illness, social class etc

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

Why Is Compliance To antipsychotic Medication Important?

Continuous treatment is associated with best

outcome
Non-compliance is associated with sub-

optimal outcome and relapse

Stopping medication is the most important

predictor of relapse
Relapse is associated with significant

morbidity
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Impact Of Partial Compliance

Impact on illness
Full Recovery
Incomplete recovery Negative Symptoms Positive Symptoms Relapse Optimal Demoralization Loss of confidence Loss of job Family discord

Rehospitalization
Relapse Danger to self/others

Days

Weeks

Months

Duration of missed doses

Keith & Kane J Clin Psychiatry, 2003; 64: 1308-1315

Continuous vs intermittent maintenance: 1 year relapse rates

Carpenter, et al. Herz, et al. Jolley, et al. Pietzcker, et al. Schooler, et al.
7 30 15 35 20 32 10 29 33 55

Continuous therapy Intermittent therapy

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 15 10 5 0 Compliant Non-compliant
Novak-Grubic & Tavcar P. Eur Psychiatry 2002;17:148-54

Relapse Well

Partial compliance is a serious obstacle to optimal outcome

Partial compliance affects the majority of patients with schizophrenia regardless of treatment Partial compliance cannot be accurately assessed Impact of partial compliance Clinical worsening in symptoms Rehospitalisation and relapse Increased risk of suicide Increased costs

Strategies to help maintain compliance

Psycho-education of patients, families and carers

Diagnosis/illness treatment possible side effects link between non-compliance- relapse-consequence of relapse

Specialised clinics and regular contact between patients caregivers

Effective medication with few side effects Use of Long-acting injectable formulations.

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The GAIN Acceptance Approach

Goal: discuss personal life & treatment goals with patient Action: With patient & family assess and consider actions necessary to achieve goals Initiate: New treatment plan Nurture: Maintain the treatment plan and patients motivation for change

Interventions To Enhance Adherence-1

Behavioural techniques: *Simplify regime *Depot medication *Behavoioural prompts *Reinforcement strategies *Rehearsal *Monitoring and diary keeping

Interventions To Enhance Adherence-2

Cognitive techniques: *Diary keeping to develop a realistic appraisal of progress *Identifying and challenging negative automatic thoughts (NATs) *Identifying action plans for high-risk situations *Reframing and modifying underlying beliefs

Patients Who Might Benefit From a Long-Acting Injectable Atypical Antipsychotic

Patients with a recent onset of schizophrenia who require long-term treatment Partially compliant patients Patients with substance use disorders Aggressive or violent patients Patients who experience or are at risk for several or severe side effects with another antipsychotic

Factors to consider in clinical decisions

Oral Antipsychotics
Unknown compliance prevents evaluation of medication effectiveness
Change medication? Increase dose? Augment?

Atypical vs. typical

No consistent significant differences exist between compliance with oral atypical or oral conventional Use of atypical antipsychotics associated with improved outcome Known adherence allows evaluation of medication effectiveness Missed dose can trigger intervention

Long-Acting Injectables

Long-acting therapy demonstrates favorable pharmacokinetics

Confidence in medication availability
Predictable, stable, and sustained plasma levels Lower peak plasma levels, less fluctuation No first-pass metabolism A missed injection (noncompliance) is immediately known

Advantages for patients

Freedom from daily pill-taking regimen Consistent contact with treatment team

Patients Prefer Long-Acting Antipsychotics

90 80 70 60 50 40 30 20 10 0
Patient Preference by Formulation
80 62 59 53
58%

63 56

Patients preferring conventional depot Patients preferring conventional oral

Patients (%)

33 23 3 20 9

0
Desai 1999 (n = 143)

Patients preferring oral atypical

Hoencamp Pereira Eastwood Jacobsson Wistedt 1995 1997 1997 1980 1995 (n = 81) (n = 107) (n = 100) (n = 43) (n = 73)

Netherlands

UK

UK

Sweden

Sweden

UK

Walburn et al. Br J Psychiatry. 2001;179:300-307.

Changing the Scenario in Schizophrenia ...Changing the Paradigm of Treatment

Efficacy in POSITIVE, NEGATIVE and AFFECTIVE symptoms

Low EPS Very low TD Low metabolic risk

Long Acting Formulation:

ADHERENCE Constant coverage

Early warning signs of partial compliance may be confused by some clinicians with non-response to treatment and may result in switching these patients to alternative oral antipsychotic medication, adding adjunctive medication,or,even worse, relapse or hospitalisation.

Strategies to improve patient compliance with antipsychotic medication are warranted in order to give patients the greatest opportunity for success, even for patients receiving the newer oral atypical agents.

The need for earlier recognition, intervention, and future prevention of partial compliance by clinicians is essential to successful treatment of our patients with schizophrenia.

Thank you