Ogbonna Nkiru

ADHERENCE IN A NIGERIAN PSYCHIATRIC HOSPITAL

ODO HILLARY OKWY

PG/M.PHARM/08/48381

Ogbonna Nkiru

Digitally Signed by: Content manager’s

DN : CN = Webmaster’s name

O= University of Nigeri

OU = Innovation Centre

FACULTY OF PHARMACEUTICAL SCIENCES

DEPARTMENT OF CLINICAL PHARMACY AND

PHARMACY MANAGEMENT

DRUG UTILIZATION REVIEW AND MEDICATION

ADHERENCE IN A NIGERIAN PSYCHIATRIC HOSPITAL

: Content manager’s Name

r’s name

O= University of Nigeria, Nsukka

OU = Innovation Centre

FACULTY OF PHARMACEUTICAL SCIENCES

DEPARTMENT OF CLINICAL PHARMACY AND

DRUG UTILIZATION REVIEW AND MEDICATION

ADHERENCE IN A NIGERIAN PSYCHIATRIC HOSPITAL

ii

DRUG UTILIZATION REVIEW AND MEDICATION

ADHERENCE IN A NIGERIAN PSYCHIATRIC

HOSPITAL

BY

ODO HILLARY OKWY

PG/M.PHARM/08/48381

DEPARTMENT OF CLINICAL PHARMACY AND

PHARMACY MANAGEMENT,

FACULTY OF PHARMACEUTICAL SCIENCES

UNIVERSITY OF NIGERIA,

NSUKKA

JULY 2014

i

DRUGUTILIZATION REVIEW AND MEDICATION

ADHERENCE IN A NIGERIAN PSYCHIATRIC

HOSPITAL

BY

ODO HILLARY OKWY

PG/M.PHARM/08/48381

A PROJECT REPORT SUBMITTED TO THE SCHOOL

OF POSTGRADUATE STUDIES, UNIVERSITY OF

NIGERIA

NSUKKA IN PARTIAL FULFILMENT OF

THE REQUIREMENTS FOR THE AWARD OF

MASTER OF

CLINICAL PHARMACY (M. Pharm) DEGREE OF THE

DEPARTMENT OF CLINICAL PHARMACY AND

PHARMACY MANAGEMENT, FACULTY OF

PHARMACEUTICAL SCIENCES

JULY 2014

ii

CERTIFICATION

Odo HillaryOkwy, a postgraduate student in the Department of Clinical Pharmacy

and PharmacyManagement with Registration Number PG/M.PHARM/08/48381 has

satisfactorily completed the requirements for the Master of Pharmacy Degree in the

Department of Clinical Pharmacy and Pharmacy Management, Faculty of

Pharmaceutical Sciences, University of Nigeria, Nsukka. The research work

embodied in this project report is original and has not been submitted in part or full

for any other diploma or degree of this or any other University.

Head Of Department…………….… Date………………

Prof. JM Okonta

Supervisor………………………….. Date……………….

Prof. JM Okonta

iii

DEDICATION

This work is dedicated to AlmightyGod, who makes all things possible including

this work, and to all the mentally ill patients all over the world,especially those

without any fault of theirs that are afflicted by this malady.

iv

ACKNOWLEDGEMENT

I wish to express my profound gratitude to my supervisor, Prof JM Okonta for his

patience, tolerance and support throughout the course of this work. Thanks for

giving me this privilege to work under you.

I wish to appreciate the erstwhile Head of Department of Clinical Pharmacy and

Pharmacy Management, Prof (Mrs.) CV Ukwe, for her concerns and advice. God

bless you.

I recognize in a special way your immense contribution to the success of this work,

Maxwell Adibe PhD. For helping with the analysis of the result of this research,

thanks and God bless you. Your positive criticisms were valued, Pharmacists

Udeogaranya P.O and Ubaka C.M, they helped in shaping this work.

I remember a friend, a sister and a confidant- Ruth Mokobia, Pharm.D, your

sustained love and encouragement formed the impetus that drove the perseverance

throughout the course of this work. I cannot thank you enough. You will forever be

in my heart.

Thank you so much Pharm (Bar) P.O Esan, the Director of Pharmacy, Federal

Psychiatric Hospital Benin, for giving me access to all I required to make this work

a reality.

I also appreciate my other colleagues - Pharm (Dr) WJ Edefo, Pharmacists: Annette,

Adejoke, Onosetaleand Grace for your assistance.

And to you Ambrose – a brother like no other, and Ukamaka, my sweet sister for

being there for me, for your concerns and encouragement when I thought that going

forward was not possible and returning was a great difficulty, I love you.

Above all, my special thanks to AlmightyGod, the maker of heaven and earth for

the gift of life, strength and knowledge. I return all glory to You.

v

TABLE OF CONTENTS

TITLE PAGE ..............................................................................................................i

CERTIFICATION .................................................................................................... ii

DEDICATION ......................................................................................................... iii

ACKNOWLEDGEMENT .......................................................................................iv

TABLE OF CONTENTS .......................................................................................... v

LIST OF TABLES .................................................................................................. vii

LIST OF ABREVIATIONS .................................................................................. viii

ABSTRACT................................................................................................................ x

CHAPTER ONE ........................................................................................................ 1

INTRODUCTION ....................................................................................................... 1

1.0 BACKGROUND ................................................................................................ 1

1.1 STATEMENT OF THE PROBLEM / RESEARCH QUESTIONS .................. 4

1.2 JUSTIFICATION OF STUDY .......................................................................... 5

1.3 SIGNIFICANCE OF THE STUDY ................................................................... 6

1.4 LITERATURE REVIEW .................................................................................... 7

1.4.1 DEFINITION OF PSYCHIATRIC DISORDER ............................................... 7

1.4.2 PREVALENCE OF PSYCHIATRIC DISORDERS ........................................ 7

1.4.3 CLASSIFICATION OF PSYCHIATRIC DISORDERS ................................. 8

1.4.4 DRUG UTILIZATION (GENERAL CONSIDERATION) ............................ 12

1.4.5 DRUG UTILIZATION IN PSYCHIATRY ..................................................... 15

1.4.6 IMPROVING DRUG UTILIZATION ............................................................. 17

1.4.7 RATIONAL DRUG USE ................................................................................. 19

1.4.8 THE CONCEPT OF ATC CLASSIFICATION AND DDD ASSIGNMENT . 27

1.4.9 ADHERENCE .................................................................................................. 30

1.4.10 ADHERENCE IN THE ADULT AND ELDERLY ....................................... 31

1.4.11 ADHERENCE IN CHILDREN AND ADOLESCENTS.............................. 36

vi

1.4.12 ADHERENCE TO PSYCHOTROPIC DRUGS......................................... 37

1.4.13 IMPROVING ADHERENCE .................................................................... 39

1.5 OBJECTIVES OF THE STUDY ..................................................................... 43

CHAPTER TWO ..................................................................................................... 44

METHODS ................................................................................................................ 44

2.0 STUDY DESIGN ............................................................................................. 44

2.1 SETTING ......................................................................................................... 44

2.2 DATA COLLECTION ..................................................................................... 45

2.2.1 Drug Utilization Review .................................................................................. 45

2.2.2 Medication Adherence ..................................................................................... 46

2.3 DATA ANALYSIS ........................................................................................ 47

2.3.1 Analysis of Drug Utilization Data .................................................................... 47

2.3.2 Analysis of Adherence Data ............................................................................. 49

2.4 ETHICAL APPROVAL ................................................................................... 49

CHAPTER THREE ................................................................................................. 50

RESULTS .................................................................................................................. 50

3.0 DRUG UTILIZATION DATA PRESENTATION ......................................... 50

3.1 ADHERENCE DATA PRESENTATION ....................................................... 57

CHAPTER FOUR ................................................................................................... 63

DISCUSSION AND CONCLUSION ....................................................................... 63

4.1 DRUG UTILIZATION .................................................................................... 63

4.2 ADHERENCE .................................................................................................. 66

4.3 LIMITATIONS OF THE STUDY .................................................................. 69

4.4 CONCLUSION ................................................................................................ 70

REFERENCES ........................................................................................................ 71

APPENDIX ............................................................................................................... 83

vii

LIST OF TABLES

TABLE 2.0: Drug Utilization Indicators and their Formula 48 TABLE 3.0: Patient Demographics 50 TABLE 3.1: Prescribing pattern based on WHO indicators 51

TABLE 3.2: Drug Availability 52

TABLE 3.3: Pattern of Drug consumption at the OPD 54 TABLE 3.4: Utilization of psychotropic drugs expressed as %, DDD/1000/day, and number of population 56 TABLE 3.5: Patient Demographic Characteristics 58 TABLE 3.6: Descriptive statistics, frequencies and % of medication taking behavior 60 TABLE 3.7: Level of Patient Adherence 61 TABLE 3.8: Comparisons of Patients’ Demographic Characteristics

with poor medication adherence 62

viii

LIST OF ABREVIATIONS

APED Action Program on Essential Drugs

ATC Anatomic Therapeutic Chemical Classification

DDD Defined Daily Dose

DSM Diagnostic and Statistical Manual

DU Drug Utilization

DURG Drug Utilization Research Group

EDL Essential Drugs List

FPHU Federal Psychiatric Hospital Uselu

ICD-10 International Classification of Diseases, 10th

revision

INRUD International Network on Rational Use of

Drugs

MMAS Morisky’s Medication Adherence Scale

MBDs Mental and Behavioral Disorders

Mg Milligram

n number

OTC Over The Counter

POM Prescription Only Medicine

POPU Population

RDU Rational Drug Use

SSRI Selective Serotonin Reuptake Inhibitor

ix

STR Strength

TR Text Revision

U.S. United States

USFDA United States Food and Drug Agency

UNICEF United Nations International Children’s

Emergency Fund

WHO World Health Organization

x

ABSTRACT

Background: Drug utilization research facilitates the rational use of drugs and suggests

measures to improve prescribing habits. Irrational use of drugs is a global problem affecting

patient care. It results in increased mortality, morbidity, adverse drug events, and wastage of

economic resources.The success of medication treatment is dependent on a patient’s

adherence to the medication regimen and non-adherence amongst psychiatric patients is

associated with poor clinical outcomes and high resource utilization.

Objectives: The objectives of this study were to evaluate the pattern of drug utilization and

the level of patients’ adherence to psychotropic drugs in a Nigerian Psychiatric Hospital.

Methods: Based on the WHO core indicators of rational drug use, data was obtained

retrospectively from a review of 5400 outpatient prescriptions from September 2007 to

August 2012. Data evaluation was done using the WHO guideline for assessment of drug

use in health facilities. Furthermore, Morisky’s scale, (an eight-item validated

questionnaire) was employed to obtain information on adherence of patients to medications

from two hundred (200) outpatients. The results were analyzed using the Statistical Package

for the Social Sciences (SPSS).

Results: A total number of 5400 prescriptions were used in this study. The pattern of

prescription in the facility revealed that an average of 2.88 drugs was prescribed per

encounter, 94.38 % of the drugs were prescribed by their generic names, and 36.13% of the

prescriptions had injection prescribed. The percentage of encounters with antibiotics

prescribed was 2.6% while 99.4% of all the drugs encountered were prescribed from the

essential drugs list.

The drugs whose utilization accounted for about 90% of the entire drug use (DU90%)

include Haloperidol, Amitriptyline, Benzhexol, Trifluoperazine, Chlorpromazine and

Carbamazepine. Haloperidol was the most utilized drug in the setting with a DDD/ 1000

inhabitants /day of 5. In more than 70% of the prescriptions encountered, all the drugs

prescribed were available in the hospital pharmacy. With respect to patient adherence,

55.5% of patients were classified as having low adherence, 36% with moderate adherence

and 8.5% having high medication adherence level.

Conclusion: The drug utilization review at the psychiatric hospital, Uselu found that

polypharmacy was frequently practiced while haloperidol was the most utilized drug. About

70% of the prescribed drugs were available at the hospital pharmacy. Outpatients’

adherence to medications was very low while socio-demographic features of patients did not

affect adherence.

1

CHAPTER ONE

INTRODUCTION

1.0 BACKGROUND

Drug utilization research has been defined by the World Health Organization

(WHO) as “the marketing, distribution, prescription and use of drugs in a society

with a special emphasis on the resulting medical, social and economic

consequences’’.1 The principal aim of drug utilization research is to facilitate the

rational use of drugs in population and to suggest measures to improve prescribing

habit. Irrational use of drugs is a widespread global phenomenon cutting across all

levels of care. This results in increased mortality, morbidity, adverse drug reactions

and economic wastages. Medicines are pivotal to healthcare delivery and disease

prevention therefore, the availability and affordability of good quality drugs coupled

with their rational use is fundamental to effective healthcare delivery in any

country.2 However, irrational use of medicines are regular occurrences in many

countries especially developing ones due to irrational prescribing, dispensing and

administration of medications.2,3According to the World Health Organization, more

than half of all medicines are prescribed, dispensed or sold inappropriately and that

half of all patients fail to take them correctly4 giving rise to patients poor clinical

outcomes.

The manner of drug use by patients and the outcomes of therapy, however, depend

on the quality and level of commitment and professionalism displayed by health care

providers. To ensure rational prescribing and drug use, the prescriber should

endeavor to follow a standard process of prescribing in accordance with that of

standard treatment guidelines and the formulary of the health care institution.

2

Rational drug dispensing requires that system of drug procurement and supply be

performed on a professional and efficient manner. The requirements for rational

drug use are that the right drugs shall be used for the right indications in the right

dose and dosage form for the right duration. Rational drug use, as an essential

element of a national drug policy seeks to avoid the frequent problems of under or

over prescription, inappropriate prescribing and the use of new, expensive drugs

when equally effective, well tried, safe and cheaper alternatives are available.

The pioneers of drug utilization research understood that a correct interpretation of

data on drug utilization requires investigations at the patient level. It became clear

that we need to know the answers to the following questions: why drugs are

prescribed; who the prescribers are; for whom the prescribers prescribe; whether

patients take their medicines correctly; what the benefits and the risks of the drugs

are?Drug utilization is in the very focus of discussion from the economic, political

and healthcare view points. A comprehensive insight into drug utilization as an

economic and primarily a public health issue can only be acquired in the context of

overall health state of the respective population.5

On the other hand, adherence to medication regimen has been monitored since the

time of Hippocrates.6 It has become a focus of increasing concern in the treatment of

psychiatric disorders in recent years.7 Adherence to a medication regimen is

generally defined as the extent to which patients take medication as prescribed by

their health care providers.6 It includes data on dose taking (taking the prescribed

number of pills each day) and the timing of doses (taking pills within a prescribed

period).Non-adherence to treatment is the degree to which a patient does not carry

3

out the clinical recommendations of the treating physician.8 Non-adherence is a

significant problem in all patient populations from children9 to elderly.10

Adherence rates are typically higher among patients with acute conditions as

compared to those with chronic conditions.11This tends to worsen the longer a

patient continues on drug therapy.12 Adherence to medication regimens necessary

for therapeutic benefit is posing a major concern to health care professionals. The

promotion of out-patient therapy and responsible self-medication has led to placing

greater responsibility on the patients for their own health outcomes. Non-adherence

is a polyfaceted problem but a triadic model relating therapeutic relationship

between the patient and clinician, factors related to medications and factors related

to the patients and their illness help to explain the non-adherent behavior.13

Physicians contribute to the non-adherence by failing to prescribe simple regimens,

not explaining the benefits and side effects of medication, not considering patients

life style or medication cost involved and inadequately eliciting and rectifying the

myths and beliefs held by patients.13,14

According to Cramer et al15, typical reasons for not taking medications include:

forgetfulness, other priorities, decision to omit doses, lack of information and

emotional factors. Supervision by a clinical trustee in cases of absence of insight on

patient’s behalf is a significant factor for adherence as well.16Non-adherence also

has economic implications. Poor adherence to medication regimen accounts for

substantial worsening of disease, death and increased health care costs.17 Of all

medication related hospital admissions in the United States, 33 to 69 percent are due

to poor medication adherence with a resultant cost of approximately $100 billion a

year.18 In less developed part of the world, cost of treatment and medication

4

deserves greater attention as patients pay almost exclusively out-of-pocket in the

absence of well-developed public health care and insurance cover.

1.1 STATEMENT OF THE PROBLEM/RESEARCH QUESTIONS

The prevalence of psychiatric disorders in both developed and developing countries

has been documented to be very high and there is a large burden of unmet need for

care among people with serious disorders.19-22The drug utilization among this class

of patients has been largely described as inappropriate which results from irrational

prescribing, dispensing and administration of medications.23

The success of medication treatment is dependent on a patient’s adherence to the

medication regimen. Non-adherence among the psychiatric patients, which has been

identified in several studies, is responsible for the poor clinical outcomes and high

resource utilization seen in this patient population.34-38

The findings following several works done on this subject matter revealed irrational

drug utilization and poor patient adherence in psychiatric settings, therefore, the

following questions are then raised about Psychiatric Hospital, Uselu, Benin City:

1. What is the current drug utilization pattern at the Federal Psychiatric

Hospital, Uselu?

2. What is the level of drug availability at the hospital pharmacy?

3. What is the current level of adherence to psychotropic drugs by patients at

the Psychiatric Hospital, Uselu?

4. What are the factors responsible for non-adherence in this setting and how

can the factors be addressed?

5

1.2JUSTIFICATION OF STUDY

Drug utilization review assesses the patterns of drug use in a particular clinical

context and such evaluation can identify problems in drug use, reduce adverse drug

reactions, optimize drug therapy and minimize drug-related expenditures.61

This can be achieved by examining the quantitative and qualitative aspects of drug

utilization. These include the medical, social and psychological factors and

consequences of drug use in relation to specific patient groups and specific

population groups, as well as the population in general.64

A major goal of drug utilization research is the improvement of drug therapy and the

assessment of drug use in the population as a whole, encompassing both

prescription-based and self-administered medications. In addition, drug utilization

research also fulfills an important public health role by not only monitoring and

controlling drug expenditure, but also providing data that serve to answer health

policy questions as well as contributing to the management and planning of public

health policies.64

In the United States, just like in many other countries, non-adherence is a serious

problem causing thousands of premature deaths and demanding care that would have

been unnecessary.64 One hundred and twenty five thousand (125 000) Americans die

annually (i.e three hundred and forty two people daily) as a result of poor

medication adherence.65Furthermore, non-adherence is the most common cause of

treatment failure which in turn affects the psychological well-being of a patient66.

Failure of the medication treatment may lead the clinician to decide on alternative

therapies which might lead to elimination of potentially effective medications or

may expose the patient to risks of adverse effects of drugs. The patient on the other

6

hand may turn to other clinicians or sources (traditional medicine for instance) for

cure. This results in more danger to the patient as well as an increase in disease-

related medical costs.

The local data on both drug utilization and patient adherence at the Federal

Psychiatric Hospital, Uselu, Benin City are very scanty. The studies done on

adherence by James and Omoaregba and drug prescribing by Agbonile and

Famuyiwawere both conducted in 2009.39,49 Therefore, there is a need to ascertain

the current level of patients’ adherence in this setting and also to re-examine the

factors responsible for poor adherence. Moreover, the previous study on drug

prescribing did not use the WHO core drug use indicators in assessing the

prescription pattern. The WHO drug use indicators which were employed in this

study allow comparison to be made between the prescription pattern of prescribers at

the Psychiatric HospitalUseluand that of the WHO reference standard and this will

go a long way in influencing the prescribers’ pattern of prescribing.

1.3 SIGNIFICANCE OF THE STUDY

It is hoped that the findings of this study would help both patients and practitioners

better understand the factors responsible for non-adherence in this setting and how

such factors could be addressed in a more collaborative manner.

It would also help the prescribers adjust their prescription pattern to be in tune with

the WHO reference standard. This study will also reveal other drug use grey areas to

which future drug use intervention programs by both the government and other

bodies could be centered on.

7

1.4 LITERATURE REVIEW

1.4.1 DEFINITION OF PSYCHIATRIC DISORDER

The simplest way to conceptualize a psychiatric disorder is as a disturbance of

cognition (i.e. thought) or conation (i.e. action) or affect (i.e. feeling) or any

disequilibrium in the three domains. Another way to define a psychiatric disorder is

as a clinically significant psychological or behavioral syndrome that causes

significant distress (subjective symptomatology), disability (objective

symptomatology) or loss of freedom; and which is not merely a socially deviant

behavior or an expected response to a stressful life event (e.g. loss of a loved

one).Conflicts between the society and the individual are not considered mental

disorders. A mental disorder should be a manifestation of behavioral, psychological,

and/or biological dysfunction in that person.135

1.4.2 PREVALENCE OF PSYCHIATRIC DISORDERS

The results of a prospective study on the prevalence of psychiatric disorders in the

Dutch population aged 18-64 revealed that psychiatric disorders were quite

common.19

According to the study, 41.2% of the adult population under 65 had experienced at

least one DSM-IV-TR135 disorder in their life time, among them, 23.3% within the

preceding year. No gender differences were found in overall morbidity. Depression,

anxiety and alcohol abuse and dependence were most prevalent and the study also

revealed a high degree of co morbidity. The prevalence rate encountered for

schizophrenia was lower (0.4% life time) than generally presumed.

8

Mental disorders are also common in the United States and in a given year

approximately one quarter of adults were diagnosable with one or more disorders.20

While mental disorders are widespread in the population, the main burden of illness

is concentrated among a much smaller proportion (about 6 percent, or in 1 in 17)

who suffer from a seriously debilitating mental illness. A 12-month prevalence of

mental disorders among U.S adult population is 26.2% while 22.3% of these (e.g.

5.8% U.S. adult population) are classified as severe.21

“Lifetime and 12-month prevalence of mental disorders in the Nigerian survey of

mental health and well-being” was a study conducted to ascertain the prevalence of

mental disorders in Nigeria. Of the 4984 people interviewed (response rate 79.9%)

12.1% had a lifetime rate of at least one DSM-IV disorder and 5.8% had 12 month

disorders. Anxiety disorders were the most common (5.7% lifetime, 4.1% 12-month

rates) but virtually no generalized anxiety or post-traumatic stress disorders were

identified. Of the 23% who had seriously disabling disorders, only about 8% had

received treatment in the preceding 12 months. The study concluded that the

observed low rates of psychiatric disorders seem to reflect demographic and

ascertainment factors. And that there was a large burden of unmet need for care

among people with serious disorders.22

1.4.3 CLASSIFICATION OF PSYCHIATRIC DISORDERS

The two major classifications in psychiatry are the ICD-10 (International

Classification of Diseases, 10th Revision, 1992)23 and the DSM-IV-TR (Diagnostic

and Statistical Manual of Mental Disorders, IV Edition, Text Revision, 2000).135

While ICD-10 is the WHO’s classification for all diseases (and not only psychiatric

disorders), DSM-IV-TR is the American Psychiatric Association’s classification of

9

mental disorders. ICD-10 will be adopted for classification of psychiatric disorders

in this study because it has been tested extensively all over the world (51 countries,

195 clinical centers), and has been found to be generally applicable across the globe.

Chapter “F’’ of the ICD-10 classifies psychiatric disorders as mental and behavioral

disorders (MBDs) and codes them on an alphanumeric system from F00 to F99.23

F00-F09: Organic, including symptomatic mental disorders

This group includes mental and behavioral disorders due to demonstrable cerebral

disease or disorder, either primary (primary brain pathology) or secondary (brain

dysfunction due to systemic disease). The disorders in this section include: delirium,

dementia, organic amnestic syndrome, and other organic mental disorders.

F10-F19:Mental and behavioral disorders due to the use of one or more

psychoactive substances

The disorders that constitute this class include: acute intoxication, harmful use,

dependence syndrome, withdrawal state, amnestic syndrome, and psychotic

disorders due to psycho-active substance use.

10

F20-F29: Schizophrenia, schizotypal and delusional disorders

This group includes mental and behavioral disorders characterized by prominent

disturbance of thought, perception, affect, and/or behavior.

The disorders in this section include: schizophrenia, schizotypal disorder, persistent

delusional disorders, acute and transient psychotic disorders, induced delusional

disorder and schizoaffective disorders.

F31-F39: Mood (affective) disorders

This group includes mental and behavioral disorders characterized by a prominent

disturbance of mood. The disorders in this section include manic episode, depressive

episode, bipolar affective disorder, recurrent depressive disorder and persistent

mood disorder.

F40-F48: Neurotic, stress-related and somatoform disorders

This group comprises mental and behavioral disorders that were earlier labeled as

neurotic disorders with an emphasis on psychological causation.

The disorders here include: anxiety disorders, phobic anxiety disorders, obsessive

compulsive disorder, dissociative (conversion) disorders, somatoform disorders,

reaction to stress and adjustment disorders, and other neurotic disorders.

F50-F59: Behavioral syndrome associated with physiological disturbances and

physical factors

This group includes mental and behavioral disorders that were earlier called

psychosomatic disorders. The disorders in this section include: eating disorders,

non-organic sleep disorders, sexual dysfunctions (not caused by organic disorder or

11

disease), mental and behavioral disorders associated with puerperium and abuse of

non-dependent producing substances.

F60-F69: Disorders of adult personality and behavior

This group includes mental and behavioral disorders that are the persistent

expression of an individual’s characteristic lifestyle and mode of relating to self and

others.

This group comprises: specific personality disorders, enduring personality changes,

habit and impulse disorders, gender identity disorders, disorders of sexual preference

and psychological and behavioral disorder associated with development and

orientation.

F70-F79: Mental retardation

This group includes disorders with arrested or incomplete development of the

intellectual abilities and adaptive behavior which may or may not be associated with

other physical or mental disorder. The disorders in this section include mild,

moderate severe and profound mental retardation.

F80-F89: Disorders of psychological development

This group includes mental and behavioral disorders with an onset during infancy or

childhood and characterized by an impairment or delay in the development of

functions that are strongly related to biological maturation of the central nervous

system. The disorders here include specific disorders of speech and language,

specific developmental disorders of scholastic skills, specific developmental

12

disorders of motor function, mixed specific developmental disorders and pervasive

development disorders.

F90-F98: Behavioral and emotional disorders with onset usually occurring in

childhood and adolescence

This group includes miscellaneous mental and behavioral disorders that have an

onset in childhood and adolescence.These disorders include hyperkinetic disorders,

conduct disorders, mixed disorders of conduct and emotions, tic disorders and other

disorders.

1.4.4 DRUG UTILIZATION (GENERAL CONSIDERATION)

The principal aim of drug utilization research is to facilitate the rational use of drugs

in population1 and to suggest measures to improve prescribing habit. Irrational use

of drugs is a widespread global phenomenon cutting across all levels of care. The

consequences of irrational medicines use include increased mortality, morbidity,

adverse drug reactions as well as economic wastages.

Drug utilization and pharmacoepidemiological studies in different countries and

practice settings during the last twenty five years have basically tried to describe

who are using the drugs and how much are being used.61 On a macro level, factors

influencing drug consumption include but not restricted to: the size of population,

age and gender distributions, occupational structure, income levels, availability of

health services, number and type of health facilities, number and type of personnel,

social insurance and reimbursement mechanisms.61

13

However, the pioneering work of Arthur Engel and Pieter Sideriusin Sweden and

Holland26respectively alerted many investigators to the importance of comparing

drug use between countries and regions. Their demonstration of the remarkable

differences in the sales of antibiotics in six European countries between 1966 and

1967 inspired WHO to organize its first meeting on “Drug consumption” in Oslo in

1969.27This led to the constitution of the WHO European Drug Utilization Research

Group (DURG).

The ultimate goal of drug utilization research must be to assess whether drug therapy

is rational or not. To reach this end, methods of auditing drug therapy towards

rationality are very pertinent. Drug use studies have also been used to identify

different types of ‘irrational’ use, e.g. overuse of psychotropics and antibiotics (such

as people using them when not indicated, for too long periods, habitual use of

analgesic every morning without a medical reason).

There has also been a lot of interests on the ‘underuse’ of drugs for major chronic

diseases like hypertension, diabetes and elevated lipids ( not starting or stopping

treatment, unsupervised drug holidays, taking only half of what is prescribed etc.)

Underuse together with misuse has been one of the main focuses of many studies62.

From some of those studies, we know something about the use of medicines, and its

clinical, social, and economic consequences.61

Drug utilization research also provides insight into the efficiency of drug use, i.e.

whether a certain drug therapy provides value for money and the results of such

research can be used to help to set priorities for the rational allocation of health care

budgets. Rational use of drugs, however, implies the prescription of a well-

documented drug at an optimal dose,along with the correct information at an

14

affordable price. Without knowledge of how drugs are being prescribed and used, it

is difficult to engage in a meaningful discussion on rational drug use or to suggest

measures to improve prescribing habits. Therefore, drug utilization research can

increase our understanding of how drugs are being used as follows.27

a. It can be used to estimate the numbers of patients exposed to specific drugs

within a given time period. Such estimates may either refer to all drug users,

regardless of when they started to use the drug within the selected period.

b. It can describe the extent of use at a certain moment and/or in a certain area

(e.g. in a country, region, community or hospital) such descriptions are most

meaningful when they form part of a continuous evaluation system, i.e. when

the patterns are followed over time and trends in drug use can be discerned.

c. Researchers can estimate (e.g. on the basis of epidemiological data on a

disease) to what extent drugs are properly used, overused or underused.

d. It can determine the pattern or profile of drug use and the extent to which

alternative drugs are being used to treat particular conditions.

e. It can be used to compare the observed patterns of drug use for the treatment

of a certain disease with current recommendations or guidelines.

f. It can be used in the application of quality indicators to patterns of drug

utilization. An example is the DU 90% (Drug utilization 90%).

The DU 90% segment reflects the number of drugs that account for 90% of

drug prescriptions and the adherence to local or national prescription

guidelines in this segment. This general indicator can be applied at different

levels (e.g. individual prescriber, group of prescribers, hospital or region) to

obtain a rough estimate of the quality of prescribing.

15

g. Drug utilization data can be fed back to the prescribers. This is particularly

useful when the drug prescribing by a particular individual can be compared

with some form of “gold standard” or best practice and with the average

prescriptions in the relevant country, region or area.

h. The number of case reports about a drug problem or adverse effects can be

related to the number of patients exposed to the drug to assess the potential

magnitude of the problem. If it is possible to detect that the reaction is more

common in a certain age group, in certain conditions or at a given dose level,

improving the information on indications, contra-indications and appropriate

dosages may be sufficient to ensure safer use and avoid withdrawal of the

drug from the market.

A review of the study conducted by Babalola et al in Osun State, Nigeria

showed that polypharmacy practice is high at the grassroots in Osun State

(south west) Nigeria.30 The study also revealed that there is shortage of

highly skilled manpower such as doctors and pharmacists for qualitative

healthcare delivery at grassroots. It also showed that the use of antibiotics

and injections were too high and there may therefore be the need to establish

protocols for the prescription and administration of both antibiotics and

injections.

1.4.5 DRUG UTILIZATION IN PSYCHIATRY

Utilization of psychiatric drugs is often a subject of drug utilization

studies.28Increasing researchers interest in prescribing and utilization of psychiatric

drugs is noted worldwide.28 Over the last decade, drug utilization studies on the

usage of psychiatric drugs have been conducted. These studies have addressed

16

certain major issues: drug use patterns, prescribing behavior, gaps between

guidelines and actual utilization and factors responsible for poly-pharmacy.28

In a review of some of the studies done in Serbia, it revealed a trend of domination

of typical antipsychotic prescription and tendency towards co-prescribing (especially

within the same class), low consumption of antidepressants and high still increasing

trend of the utilization of anxiolytic/hypnotic drugs. Among positive trends, steady

increase in the use of atypical antipsychotics and Selective Serotonin Reuptake

Inhibitors (SSRIs) antidepressants were noted.

Furthermore, a study conducted by Kapoor in 2003 at a hospital in Jammu City,

India which assessed two parameters – adherence to prescription format and

rationality of prescription, indicated that majority of prescriptions did not adhere to

the ideal pattern of prescription writing. Important demographic information like age

and sex were not written in the majority of the cases.29 He also noted that weight of

patient which is so important in calculating the dose of drug in pediatric patients was

missing in 88% of such prescriptions. Directions regarding total amount of drug to

be dispensed and instructions regarding use of drug were inadequate in 50% and

39% of the prescriptions respectively.29

Another disturbing revelation of drug utilization research is the identification of high

rate of polypharmacy especially among psychiatrists. A study done in Kaduna,

Northern Nigeria established that 92% of respondents were given two or more

psychotropic drugs.31 The high rate of psychotropic polypharmacy found in the

study above is consistent with those reported by studies from the southern

Nigeria32,33 and other parts of the world.31 That the figure is similar to those reported

by studies carried out in the country over a decade ago suggests a persistent trend in

17

the use of psychotropic polypharmacy in psychiatric practice and efforts should be

made to check and curtail this trend.

1.4.6 IMPROVING DRUG UTILIZATION

Improving the public understanding of drugs:During the last few years, there have

been different attempts both in developed and developing countries to improve the

knowledge and understanding about drugs among the general public.61This can be

seen as an attempt to influence and improve the social knowledge related to drugs

and health in general. Campaigns like ‘ask about your medicines’, are good

examples of this kind of activity. A more balanced partnership between patients and

health care providers is one of the goals in such activities. Also a better appreciation

of the limit of medicines and a lessening of the belief that there is a ‘pill for every

ill’ are examples of the goals of such efforts.

The general public also needs to develop a more critical attitude toward advertising

and other commercial information, which may often fail to give objective

information about drugs. Drug use should be seen within the context of a society,

community, family and individual, recognizing cultural diversity in concepts of

health and illness or how drugs work. Improvement of the public’s knowledge about

drugs should start at school. To facilitate informed choices on drug use, public

education should be accompanied by supportive legislation and controls on drug

availability. Effective public education requires a commitment to and understanding

of the need for improved communication between health care providers and patients.

This should also be reflected in the basic and continuing education of health care

professionals.

18

Ensuring the safety ofdrugs:Because most people will use medicines and related

services in a regular basis, the functioning of the sector is of utmost common

interest. There are also many parties involved- patients, healthcare providers,

manufacturers and sales representatives and therefore, detailed rules for interaction

and functioning is highly required. History has shown that informal controls are not

sufficient or respected.69

Legislation and regulation include different health-related laws, pharmacy law,

trademark and patent laws, criminal law, international treaties ( e.g. on narcotic and

psychotropic drugs) and government decrees. Sometimes there may be a lack of

political will or a weak infrastructure to enforce the laws as is the case in most of the

developing countries. When looking at the legal situation in the drug sector in

different countries the problem seem to be more often in the enforcement of

legislation than the lack of lagislation61

Drug registration is a key tool in assuring the safety, quality and efficacy of a new

drug being introduced into the market. In this connection the new medicine will also

be scheduled to a certain category such as POM or OTC drugs. The infrastructure

that will assure drug quality, safety and efficacy can be ascertained by licensing and

inspection of manufacturers, distributors and the premises, and also by setting some

standards on the professionals working there.

Pharmacoepidemiological studies are used to assure the safety of new medicines

after theyhave been accepted on the market. This kind of information can

supplement that availablefrom premarketing studies, it can also give a better

quantification of the incidence of known adverse drug reactions but also beneficial

effects. For ethical and other reasons it is not always suitable to perform clinical

trials on certain patient groups such as children, elderly, and pregnant women in the

19

early phase of a new product. It is also important to establish how other medicines

and diseases may alter the positive effects. New types of information not available

from the premarketing studies such as rare undetected adverse drug reactions, long

term effects that manifest only after long use, and effects with low frequency are

also the concern of pharmacoepidemiological studies.

Ensuring the availability of medicines: Availability of medicines is one of the key

requirements in a functioning drug service system.61This includes a functioning

manufacturing and importation system of medicines, good procurement and

distribution practices. In developing countries, the maintenance of a constant supply

of medicines, keeping them in good condition, minimizing losses due to spoilage

and expiry (by observing, for instance the rule of ‘ first to expire first out’ and the

use of reorder levels in drug procurement), are issues that need to be solved to assure

the availability of medicines to the population.

1.4.7 RATIONAL DRUG USE

Rational drug use (RDU) is defined as the use of an appropriate, efficacious,safe and

cost-effective drug given for the right indications in the right dose and formulation,

at right time intervals.70The promotion of rational drug use involves wide range of

activities such as adaptation of the essential drug concept, continuous training of

health professionals and the development of evidence based clinical guidelines.

Unbiased and independent drug information, consumer education and regulatory

strategies are also essential to promote rational drug use.71 Drug related problems

include medication error (involving an error in the process of prescribing, dispensing

20

or administering a drug, whether there are resultant adverse consequences ornot),

adverse drugreactions (any response to a drug which is noxious and unintended, and

which occurs at doses normally used in humans for prophylaxis, diagnosis or

therapy of disease, or for the modification of physiologicalfunctions) and drug

interactions.72These drug- related problems are frequent and may result in reduced

quality of life, and even increasedmorbidity and mortality.73The overuse, underuse

or misuse of medicines result in wastageof scarce, economic resources and

widespread health hazards. Examples of irrational use of medicinesinclude: use of

too many medicines per patient ("poly-pharmacy"); inappropriate use of

antimicrobials, often in inadequate dosage, for non-bacterial infections; over-use of

injections when oral formulations would be more appropriate; failure to prescribe in

accordance with clinical guidelines; inappropriate self-medication, often of

prescription-only medicines; non-adherence to dosing regimes.

The problem of irrational prescribing: Irrational prescribing is a global problem.100

Numerousstudies, both from developed and developing countries, describe a pattern

that includes polypharmacy74, the use of drugs that are not related to the diagnosis75

or unnecessarily expensive76, the inappropriate use of antibiotics77and irrational

selfmedication78 with drugs frequently taken in underdose.79 The problem is

worsened by a global shift from public to private sector spending, which, in many

developing countries without adequate regulation and inspection, usuallyresults in a

large proportion of drugs being purchasedwithout any prescription at all.

Measuring drug use: Rational drug use cannot be defined without a method of

measurement and a reference standard.2These same tools are even more necessary to

measure the impactof an intervention, to make comparisons between facilities,

21

districts or regions, and for supervisory purposes. Knowledge of the prescriber has

sometimes been used as an output measure of interventions.80However, adequate

knowledge on rational drug usedoes not always result in rational prescribing

behavior. Actual behavior is therefore preferred as a measurement. Over the past

few years, the International Network for Rational Use of Drugs (INRUD) and the

WHO Action Programme on Essential Drugs (APED) have closely collaborated in

developing and testing a set of 12 quantitative indicators to measure some key

aspects of prescribing and the quality of care.81These indicators, which are now also

recommended by UNICEF, are listed below. A detailed manual on their use is

available from WHO.82The second important requirement in studyingrational drug

use is a standard. In practice this implies that the prescriptionshould be compared

with an agreed treatment protocol or with a list of therapeutic alternatives. This is

also a core principle of medical audit. The following are the Drug use indicators82

Prescribing indicators 1 Average number of drugs per encounter 2 Percentage of drugs prescribed by generic name 3 Percentage of encounters with an antibiotic prescribed 4 Percentage of encounters with an injection prescribed 5 Percentage of drugs prescribed from essential drugs list orformulary

Patient care indicators 6 Average consultation time 7 Average dispensing time 8 Percentage of drugs actually dispensed 9 Percentage of drugs adequately labeled

22

10 Patient knowledge of correct dosage

Facility indicators 11 Availability of copy of essential drugs list or formulary 12 Availability of key drugs

Strategies to promote rational prescribing and their possible impact

The various interventions used in promoting rational prescribing are best classified

as educational,managerial and regulatory.83 Educational strategiesinclude printed

materials, seminars,bulletins and face-to-face interventions. Managerial methods

refer to various restrictions onprescribing, e.g. restrictive lists, a maximum number

of drugs per prescription, budgetary or cost restrictions, endorsement by higher

qualified consultants, patient co-payment strategies,price measures, structured

prescription forms or a maximum duration for inpatientprescriptions (automaticstop-

orders). Regulatory measures include procedures to critically evaluate drugs and

productinformation (e.g. data sheet, patient information leaflet) before market

approval is granted, scheduling drugs for different sales levels (over the

counter,pharmacy only, prescription only) and specifying for each drug a minimum

level ofprescriber or health facility (for example, no injectible antibiotics at health

centers).

Several studies have critically reviewed the available evidence to identify the most

effectiveinterventions84, and the following provisional conclusions may be drawn.

An importantobservation is that printed materials alone hardly influence prescriber

behaviour85, and that any such influence is usually of short duration.86 Most of these

interventions assume that the main reason for incorrect prescribing is a lack of

23

knowledge and that ifprescribers had the correct information, their prescribing

would automatically improve. This is not always the case in view of the many other

factors influencing prescribing, like drug promotion by pharmaceutical

representatives, patient demand, intentional use of placebo drugs and prescriber

preference based on personal experience rather than peer reviewed standards.87

Technical information on cost and side effects of the drugs is of much less influence,

as shown in the Netherlands.88 Another aspect of the problem is that prescribers with

irrational prescribing behavior are the very ones that are less likely to read the

educational material mailed to them. Proven cost-effective interventions are face-to-

face education focused on a particular prescribing problem in selected individuals89,

structured prescription forms90, and focused educational campaigns together with

widely discussed and frequently revised treatment guidelines. An example of the

latter is the success of the Australian antibiotic guidelines.91 Most recently, a review

of 59 published evaluations of the effect of clinical guidelines concluded that all but

four of these studies detected significant improvements in the process of care after

the introduction of guidelines, and all but two of the 11 studies that assessed the

outcome of care, reported significant improvements. However, the size of the

improvements in performance varied considerably.92

Essential drugs lists together with an educational programme and follow-up are

probably effective as well. As mentioned above, most evidence suggests that printed

materials alone are ineffective.85,86,88 It is likely that this also applies to essential

drugs lists and treatment guidelines if these are just distributed to prescribers without

an introduction campaign and without intensive follow-up, and especially if the

24

prescribers had not been involved in the development process. A general problem is

that many interventions have only been tested in developed countries and that the

results can therefore not automatically be extrapolated to developing countries

where conditions are so different. In the absence of well conducted studies, Laing

has attempted to give provisional advice to developing countries with regard to

possible effective interventions.93 He suggests that basic and postbasic medical

education should include specific training in rational prescribing; that essential drugs

lists and therapeutic guidelines should be developed through wide consultation and

feed-back and be disseminated by means of intensive educational programmes as

recorded from Yemen94, Uganda95and Zimbabwe96; that general limitations on

prescribers(maximum number of drugs per prescriptions, maximum quantities,

maximum costs etc) may have unexpected effects which should be avoided through

careful studies before such measures are taken; that face-to-face education may be

effective but expensive; and that printed materials, including treatment guidelines,

are ineffective without educational programmes and follow-up activities. The overall

impact of drug bulletins is not clear. Experience from developed countries is not

encouraging, but this may be due to the fact that prescribers receive so many

promotional and other materials that some of them did not even recognize a

carefully designed set of academic detailing material as different fromcommercial

material.97 However, in most developing countries the lack of

information,promotional or otherwise, is so serious that any unbiased material sent

out to prescribers might be studied with more care. Bulletins, especially when

geared to actual day-to-day prescribing problems, may therefore have more impact

in developing countries than elsewhere. This hypothesis is worth examining.

25

The role of medical schools and teaching hospitals:

The impact of medical education on subsequent prescribing behavior is difficult to

evaluate, as most studies have measured knowledge rather than actual performance.

Moreover, immediately after leaving medical school the young doctors are exposed

to many other factors influencing their prescribing. It is now increasingly being

recognized that the traditional medical education concentrates too much on an

accumulating quantity of facts, including the drugs of the day, rather than teaching

the student techniques of problem solving and making a rational choice between

drug treatment alternatives, which includes the skill to evaluate critically any new

drugs of the future.98

With regard to rational prescribing this implies that the objectives of clinical

pharmacology training need to be defined better, with more emphasis on the

practical needs of the future prescriber. This has shown to result in better therapeutic

knowledge and skills of the students.99An undergraduate course in clinical

pharmacology and therapeutics should stress the principles of rational evaluation of

therapeutic alternatives and help the students to develop their own personal

formulary on the basis of a rational comparison of therapeutic alternatives. Such a

course could also 'immunize' the students against the disturbing influences they are

likely to encounter in their professional life, such as patient pressure, drug

promotion and irrational prescribing by peers. The introduction of such a revised

course in clinical pharmacology alone will not be enough. In many teaching

hospitals bedside training emphasizes the need to make a correct diagnosis, with

much less time spent on choosing the correct treatment.

26

And even if treatment guidelines exist, students are usually told to follow them

rather than being taught on what grounds the guidelines had been developed, and

how they should choose their own treatment in the future. Under these

circumstances students entering the wards can do little more than copy the behaviour

of residents and consultants. Unfortunately the prescribing practice in teaching

hospitals, that inevitably serves as a role model for the students, is often irrational

and inconsistent, as has frequently been described from developed and developing

countries. For example, numerous reports100 on the inappropriate use of antibiotics

in teaching hospitalsshows that as many as 41-91% of all antibiotic prescriptions in

teaching hospitals were considered inappropriate; a slightly better picture emerged

from medical and paediatricbwards but the situation in surgical and gynaecological

wards was usually worse. Unnecessary treatment was by far the most common

reason for irrational prescribing, followed by Wrong duration, misguided

prophylaxis and poor selection of the drug. Not only antibiotics are misused in

teaching hospitals. Polypharmacy was considered a serious problem in the medical

and surgical wards of Singapore general hospital101 and vitamins were heavily

overprescribed in the Kenyatta Teaching Hospital.75 In the teaching hospital in Aden

(Yemen) 68% of all patients with hypertension were prescribed diazepam, and 54%

received Frusemide80; 80% of patients with osteoarthritis received vitamins.

In the teaching hospital in Benin city (Nigeria) 74.3% of all pediatric prescriptions

were considered inappropriate, mostly because of polypharmacy, the use of

unnecessary drugs and suboptimal dosage schedules.102 In Ilorin teaching hospital in

Nigeria 33.1% of patients admitted to the surgical and medical wards received

psychotropic drugs, 91.4% being tranquillizers.103 The potential long term impact of

27

such a lack of structured therapeutic training in the wards should not be

underestimated. Teaching hospitals have a special responsibility towards society to

promoterational prescribing by their staff and, through these, by future generations

of doctors. The best approach seems that each clinical department in the teaching

hospital should develop a departmental prescribing policy through a process of

consultation and consensus building, in which clinical pharmacologists are involved.

Such prescribing policies can later be integrated into a hospital formulary and should

be used, and enforced, as the basis for prescribing, teaching, examinations and

medical audit. This is already the case in several medical schools in the United

Kingdom104 and elsewhere; amongst developing countries Zimbabwe is a good

example.105 Ideally, medical students would then be trained in the principles of

rational prescribing before they enter the wards; and these concepts would be

reinforcedduring the clinical training with bedside teaching, examinations and actual

prescribing by senior staff all based on the same principles.

1.4.8 THE CONCEPT OF ATC CLASSIFICATION AND DDD

ASSIGNMENT

The purpose of the Anatomical Therapeutic Chemical Classification/Defined Daily

Dose (ATC/DDD) system is to serve as a tool for drug utilization research in order

to improve quality of drug use. One component of this is thepresentation and

comparison of drug consumption statistics at international andother levels.A major

aim of the Centre and Working Group is to maintain stable ATC codes andDDDs

over time to allow trends in drug consumption to be studied without thecomplication

of frequent changes to the system. Thereis a strong reluctance tomake changes to

classifications or DDDs where such changes are requested forreasons not directly

28

related to drug consumption studies. For this reason theATC/DDD system by itself

is not suitable for guiding decisions aboutreimbursement, pricing and therapeutic

substitution.It has to be noted that the classification of a substance in the ATC/DDD

system is not a recommendation for use, nor does it imply any judgements about

efficacy or relative efficacy of drugs and groups of drugs.40 In the ATC

classification system, the active substances are divided into different groups

according to the organ or system on which they act and their therapeutic,

pharmacological and chemical properties. Drugs are classified in groups at five

different levels. The drugs are divided into fourteen main groups (first level), with

pharmacological/therapeutic sub groups (second level). The third and fourth levels

are chemical/pharmacological/therapeutic sub groups and the fifth level is the

chemical substance. The 2nd, 3rd and 4th levels are often used to identify

pharmacological sub groups when that is considered more appropriate than

therapeutic or chemical sub groups.

The complete classification of metformin, for instance, illustrates the

structure of the code.

A Alimentary tract and metabolism (1st level, anatomical main

group).

A10 Drugs used in diabetes (2nd level, therapeutic sub group).

A10B Blood glucose lowering drugs, excludinginsulins (3rd level,

pharmacological sub groups).

A10BA Biguanides (4th level, chemical sub group).

A10BA02 Metformin (5th level, chemical substance).

Thus, in the ATC system, all plain metformin preparations are given the code

A10BA02.

29

For amitriptyline.

N Nervous system (1st level, anatomical main group).

N06 Psychoanaleptics (drugs that cause arousing effect) (2nd level,

therapeutic sub group).

N06A Antidepressants (3rd level, pharmacological sub group).

N06AA Tricyclic antidepressants (4th level, chemical sub group).

N06AA09 Amitriptyline (5th level, chemical substance).

Therefore, all plain amitriptyline preparations are given the code N06AA09 in the

ATC classification system.

The DDD is defined as the assumed average maintenance dose per a day for a drug

used for its main indication in adults. A DDD will only be assigned for drugs that

already have an ATC code. It should be emphasized that DDD is a unit of

measurement and does not necessarily correspond to the recommended or prescribed

daily dose (PDD). Doses for individual patients and patient groups will often differ

from the DDD as they must be based on individual characteristics (e.g. age and

weight) and pharmacokinetic considerations.

The DDD is often a compromise based on a review of the available information

about doses used in various countries. The DDD may even be a dose that is seldom

prescribed, because it is an average of two or more commonly used dose sizes.

When drug utilization studies are carried out in an outpatient setting, the figures

should ideally be presented as numbers of DDDs per 1000 inhabitants per day which

is calculated using the following equation.

DDD/1000 inhabitants = ����������� �(��)

���(��)��������������(� )�1000

30

Prescription data presented in DDDs per 1,000 inhabitants per day may provide a

rough estimate of the proportion of the study population treated daily with a

particular drug or group of drugs. For instance, the figure 10 DDDs per 1000

inhabitants/ day indicates that 1% of the population on average might receive a

certain drug or group of drugs daily.

1.4.9 ADHERENCE

In medicine, adherence describes the degree to which a patient correctly follows

medical advice. Most commonly, it refers to the adherence to drugs or medications,

but it can also apply to other situations such as medical device use, self care, self-

directed exercises, or therapy sessions. Both the patient and health care provider

affect adherence and a positive physician-patient relationship is the most important

factor in improving adherence, 41 although the cost of prescription medications also

plays a major role.42In a study, it was found that being married, older, employed, not

smoking or drinking were associated with higher adherence62. The most common

reason given by patients for failure of adherence is being fed up with the disease and

the therapy, forgetful or too busy.63

Worldwide, non-adherence is a major obstacle to the effective delivery of

healthcare. Estimates from the World Health organization (2003) indicate that only

about 50% of patients with chronic diseases living in developed countries follow

treatment recommendations.41 In particular, low rates of adherence to therapies for

asthma, diabetes, and hypertension are thought to contribute substantially to the

human and economic burden of those conditions.41

31

Adherence rates may be overestimated in the medical literature, as adherence is

often high in the setting of a formal clinical trial but drops off in a “real world”

setting.43 Major barriers to adherence are thought to include the complexity of

modern medication regimens, poor health literacy and lack of comprehension of

treatment benefits, the occurrence of undiscussed side effects, the cost of

prescription medicine, and poor communication or lack of trust between the patient

and his or her health care provider.44,45,46 Efforts to improve adherence have been

aimed at simplifying medication packaging, providing effective medication

reminders, improving patient education and limiting the number of medications

prescribed simultaneously.

1.4.10 ADHERENCE IN THE ADULT AND ELDERLY

Age by itself is not a determining factor in medication nonadherence.50Rather, there

are many factors that may combine to render older persons less able to adhere to

their medication regimens. However, there is evidence to suggest that, with the

proper motivation, education and support, older persons can overcome many barriers

to medication adherence.50

FACTORS AFFECTING MEDICATION ADHERENCE IN THE ELDERLY

Adherence is a multidimensional phenomenon determined by the interplay of five

sets of factors, termed “dimensions” by the WHO.51The various dimensions and the

factors influencing them are as follows:

Social/Economic Dimension

- Limited English language proficiency

- Low Health literacy

32

- Lack of family or social support network

- Unstable living conditions; homelessness

- Burdensome schedules

- Limited access to health care facilities

- Lack of Health care insurance

- Inability or difficulty accessing pharmacy

- Medication cost

- Cultural and lay beliefs about illness and treatment

- Elder abuse.

Health care systems Dimensions

- Provider-patient relationship

- Provider communication skills (contributing to lack of patient knowledge or

understanding of the treatment regimen)

- Disparity between the health beliefs of the Health care provider and those of

the patients.

- Lack of positive reinforcement from the Health care provider

- Weak capacity of the system to educate patients and provide follow up.

- Lack of knowledge on adherence and of effective interventions for

improving it.

- Patient information materials written at too high literacy level

- Long waiting time

- Lack of continuity of care.

Condition-related Dimension

- Chronic conditions

33

- Lack of symptoms

- Severity of symptoms

- Depression

- Psychotic disorders

- Mental retardation/ developmental disability.

Therapy-related Dimension

- Complexity of medication regimen

- Treatment requires certain techniques ( injections/ inhaler)

- Duration of therapy

- Frequent changes in Medication regimen

- Lack of immediate benefit of therapy

- Medications with social stigma attached to use

- Actual or perceived unpleasant side effects

- Treatment interferes with lifestyle or requires significant behavioral changes

Patient-related Dimensions

a. Physical Factors

- Visual impairment

- Hearing impairment

- Cognitive Impairment

- Impaired mobility/dexterity

- Swallowing problems

b. Psychological/Behavioral factors

- Knowledge about desease

34

- Perceived risk/ susceptibility to disease

- Understanding reasons medication is needed

- Expectations or attitudes towards treatment

- Perceived benefit of treatment

- Confidence in the ability to follow treatment regimen

- Fear of dependence

- Frustration with health care providers/system

- Alcohol/substance abuse.

Patient-related factors are just one determinant of adherence behavior.The common

belief that a person is solely responsible for taking their medications often reflects a

misunderstanding of how other factors affect people’s medication-taking behavior

and their capacity to adhere to treatment regimens51. Factors associated with each

dimension are listed above.

It is clear that adherence is a complex behavioral process strongly influenced by the

environments in which people live, health care providers practice, and health care

systems that deliver care. Adherence is related to people’s knowledge and beliefs

about their illness, motivation to manage it, confidence in their ability to engage in

illness-management behaviors, and expectations regarding the outcome of treatment

and the consequences of poor adherence51.

It is important to recognize that a person may have multiple risk factors for

medication nonadherence. Also, factors that can influence a patient’s medication-

taking behavior may change over time.Therefore, it is important to continually

assess a person’s adherence throughout the course of therapy. In addition, because

35

there is usually no single reason for medication nonadherence, there can be no “one

size fits all” approach to improving adherence.

Many of the interventions used to improve adherence especially in the elderly focus

on providing education to increase knowledge; simplifying the medication regimen

(fewer drugs or fewer doses); or making it easier to remember (adherence aids, refill

reminders).

However, simplifying a dosage regimen is unlikely to affect a patient who does not

believe that taking medications is important or that the therapy will improve his/her

health, and the available evidence shows that knowledge alone is not enough for

creating or maintaining good adherence habits.51

Based on published studies52, it is evident that single interventions are less

successful than multiple, long term interventions in affecting adherence. The studies

show that the most successful interventions have some follow-up component and

address the underlying reasons for nonadherence. Comprehensive interventions

should address a variety of issues, including knowledge, motivation, and social

support and individualizing therapy based on a patient’s concerns and needs.52

The ideal time to initiate adherence interventions is when therapy first begins.

Interventions that are initiated early in the course of therapy can support older

persons through a period when they are most likely to have questions or to

experience side effects from the therapy.

36

1.4.11 ADHERENCE IN CHILDREN AND ADOLESCENTS

Poor medication adherence is common in children and adolescents with chronic

illness, but there is uncertainty about the best way to enhance medication adherence

in this group and this is due to the fact that no studies have identified effective

interventions for young people with established poor adherence.54

Most existing reviews of adherence-promoting interventions have focused on the

adults. However, many young people experience chronic illness55,56 and poor

medication adherence.54,57 Involvement of families in medication routines57,58 and

varying developmental capacities of children and adolescents59 may influence

medication adherence, reinforcing the need to identify interventions with

demonstrated efficacy in young people rather than translating findings from adult

research.54,59

A review of interventions for children suggests that educational or behavioral

interventions may be potentially effective for promoting adherence,60These

interventions are important as they are able to be implemented by individual health

practitioners at various treatment stages.

Education typically involves providing verbal or written information about the

nature of the illness, rational for treatment and benefits and adherence while

behavioral management includes a range of techniques such as monitoring and goal

setting, reinforcing medication taking with rewards, problem solving and linking

medication taking with established routines.

37

1.4.12 ADHERENCE TO PSYCHOTROPIC DRUGS

Enhancing a patient’s adherence to psychotropic medication regimens is one of the

challenges facing all mental health professionals and consequently has been studied

for over fifty years.53Mitchell and Selmes (2007) have provided a comprehensive

account of the reasons that lead people with a wide range of mental disorders to miss

their medications. They have illustrated many factors that such individuals share

with patients with physical disorders, and also more specific to people with mental

disorders.47

Medication adherence rates reported for populations with psychiatric illness ranges

from 24 to 90 percent for patients treated with antipsychotic medication and 40 to

90 percent for patients treated with antidepressants.7 Another set of patients will

never start or will stop therapy completely within the first year and only a minority

will continue taking drugs as prescribed.12 An overview of the extensive literature

on medication adherence found no differences in adherence rates between

populations with physical disorders and those with psychiatric disorders.49

Studies that seek to ascertain the patients’ adherence to psychotropic drugs have

been carried out in different parts of Nigeria and also at other parts of the world with

varying results obtained. In most of the studies consulted, co-morbidities, side

effects, forgetfulness, high cost of medications, inability of the practitioners to

explain timing and dose or benefits of medications and educational status of the

patients were some of the factors associated with non-adherence.34-38

38

According to the study done by James and Omoaregba in 2009, their findings were

that higher frequency of medication dosing, illness severity and stigma were the

significant predictors of poor medication adherence among the psychiatric patients.39

39

1.4.13 IMPROVING ADHERENCE

One of the sections above has reviewed briefly some of the main factors which

influence the adherence of elderly patients as well as other patient categories. The

point has already been made that, ultimately, the patient has the right not to comply.

However, it may be regarded as a professional responsibility to try to persuade the

patient on the benefit of adherence. The following section considers some of the

many techniques which the pharmacist can use to achieve improved adherence.

Understanding

The aim here is to ensure as high a level of understanding by the patient as possible.

This means that optimum communication skills must be used. This can be done

orally during patient counseling. This may simply involve passing on relevant

information to the patient. However, the pharmacist need to be alert to the

indications of the patient’s health beliefs, their own objectives of the treatment and

any information they may already have acquired from other sources. If these are at

variance with fact, an attempt may be required to correct the error.

Apart from routine counseling, it may be necessary to give additional information to

fill in gaps in understanding following the patient’s consultation with the doctor.

Alternatively, it could be providing information about the disease, the drug, and

lifestyle advice or giving training in using the medicine. Where a patient relies on a

carer, it is advisable to involve the carer in any counseling or other advice which is

being given.

Along with verbal communication, written information is supplied. Labels must be

clear, easy to read and unambiguous. Where necessary and possible, computers can

40

produce print labels as well as Braille labels. Other written information must be in

non-technical language to make it readily understood.

Medicines management

When adherence aids are discussed, it is usually those designed to assist medicine

management which are thought of first. The aim of any actions taken is to assist

patients to manage their medicine-taking. There are three main approaches which

can be tried. A diary of the day, indicating on it the times at which each medicine

should be taken is the simplest form of adherence chart. Colour coding may be used

to link the medicine bottle and chart. Marking the chart as each dose is taken assists

in preventing re-administration.

Devices designed as compliance aids can be used. There is a wide range of different

designs of memory aid devices for tablets and capsules. Monitored dosage systems

can be used as an alternative. The principle on which they all operate is that

compartments are used to hold doses, each compartment corresponding to a time of

day. The patient works through the device as the day progresses, removal of the

medicine indicating that it has been remembered. Audible devices are also available.

There can be some problems. Errors may be made in filling the aid, there are

questions about the stability of some medicines in these devices and some patients

may have difficulty getting the tablets or capsules out of the compartments. Liquids

are much more difficult to handle using these aids. Some of these adherence aids

include 7-day pill organizer, Automatic pill timer, Daily pillminder, Day planner,

Medimax, Mediset mini, Medtime Minder (audible) and many more similar aids and

new ones are being introduced continually.61

41

The third possibility is to review the medicines to see if the regimen can be

simplified to make it easier to manage. Thus, the use of sustained-release dosage

forms reduces dosage frequency and combination dosage forms reduce the total

number of medicines to be remembered. It is known that going from three or four

times daily dosing to twice daily improves adherence, but there seems to be no

further advantage with once daily dosing.61

Disease-related problems

Careful counseling can answer many of the problems which arise from a lack of

understanding about the disease and its treatment. This can be particularly important

with asymptomatic conditions or prophylactic treatments. Where the disease has

reduced the manipulative ability of the patient, some adherence aids or other simple

measures may be useful. The simplest is to suggest non-child-resistant closures for

some elderly patients. Larger bottles can be used to make handling easier. Devices

are available to get tablets from blister packs, which many people with arthritis and

pakinsons disease find particularly difficult. A long-armed roller is available to

assist applying ointments and creams to parts of the skin that are difficult to reach.

Drug-related problems

Many pharmacists especially those in the community find it difficult to obtain

generics for dispensing which are almost always consistent in appearance. Thus it

may not be possible to reduce the problems that arise from changes of color, shape

and size, other than by reassuring the patient. Where some control is possible, the

use of the patient medication record to record the source of tablets dispensed for an

individual will reduce these variations to minimum and thereby improving the

patient’s adherence. Control of side effects may require a change in prescription.

42

However, it is sometimes possible to modify the method of taking a medicine to

reduce the problems, such as avoiding tablets on an empty stomach to reduce the

incidence of nausea. Where ingredients will not be acceptable to some patients, it is

necessary for the pharmacist to be aware of the problem and to be in a position to

suggest alternative products where possible.

Other problems

There are no simple answers to many of the other sociological and psychological

factors which affect adherence. The correct prescribing decision for the patient will

be more likely if a concordant approach is adopted during consultation, and

adherence should increase as the goals of the treatment are the patient’s. However,

in order that the pharmacist can provide counseling consistent with the decision of

the prescriber, mechanisms will need to be developed for the sharing of this

information, although issues of patient confidentiality and sharing of data need to be

resolved.Depending on the nature of the problem, effective counseling by the

pharmacist may assist with improving adherence. In other situations, it may require

a concerted effort by the whole health care team to help patients understand their

treatment and the personal value of compliance for them.

Adherence to medication can be a very difficult problem which may go undetected.

When non adherence is recognized, the pharmacist is in a good position to offer

support to the patient. The approach should be to attempt to remove obvious barriers

to adherence first, e.g. by suggesting adherence aids, drawing up adherence chart or

instructing in the method of administration. Some patients will always be poor

compliers, but many can be helped towards effective use of their medicines.

43

1.5OBJECTIVES OF THE STUDY

The general objective of this study is to evaluate the drug utilization pattern and

patients’ adherence to psychotropic medicines at the Federal psychiatric

HospitalUselu, Benin City while the specific objectives include:

1. To evaluate the drug utilization pattern using WHO drug use indicators

2. To assess theavailability of essential medicines

3. To determine the level of patients’ adherence to medications and

4. To explore the factors influencing medication adherence at the study setting.

44

CHAPTER TWO

METHODS

2.0 STUDY DESIGN

The study design employed for the drug utilization study was a retrospective

method. The retrospective method was descriptive and employed relevant data from

the prescription records of the patients seen in the out-patient pharmacy section of

psychiatric hospital, Uselu from September 2007 to August 2012.

Data on WHO core drug use indicators and the percentage of drugs prescribed but

not available (i.e out of stock) were collected during the study.

The other arm of the study which was a prospective design employed Morisky's

scale67 to assess the patients’ level of medication adherence.

2.1 SETTING

This study was conducted at the Federal Psychiatric Hospital Uselu, Benin City, Edo

State.The hospital has a 220-bed capacity and serves about thirteen million49 people

living in the state and neighboring states of Delta, Ondo, Anambra, Kogi and

Rivers.The hospital, in August 2012, has in its employ six(6) Consultant

psychiatrists, nineteen(19) resident Doctors, oneDoctor on Youth Service,

Thirteen(13) Pharmacists, two Pharmacists, twelve (12) Intern Pharmacists, five(5)

Pharmacy Technicians, one hundred and seventy three(173) Nurses, one(1) clinical

Psychologist and other Healthcare professionals.

45

2.2 DATA COLLECTION

2.2.1 Drug Utilization Review

Systematic random sampling was adopted in collecting data for the drug utilization

study. The prescription sheets of patients seen at the OPD section of the pharmacy

department between September 2007 and August 2012 were collected and collated

chronologically and later separated according to the year of prescription. For the

purpose of this study, September 2007 to August 2008 was referred to as year 1,

September 2008 to August 2009 as year 2, September 2009 to august 2010 as year 3,

September 2010 to august 2011 as year 4 and September 2011 to August 2012 as

year 5.

The total number of prescriptions over the five-year period was 108000 with an

average of 48,57,60,60 and 75 prescriptions per day giving rise to 17280, 20520,

21600, 21600, and 27000prescriptions respectively for each year. From the 108000

total prescriptions that was collated and classified according to the year of

prescription, 3 prescriptions were selected at random by picking 1 in every 16

prescriptions for the first year, 1 in every 19 prescriptions for the second year, 1 in

every 20 prescriptions for the third and fourth years and 1 in every 25 prescriptions

for the fifth year amounting to 1080 prescriptions per year and 5400 sample

prescriptions used in this study. The relevant information on the sampled

prescriptions were entered into a data collection form (Appendix 1). The information

that were extracted from the prescriptions included: date of prescription, age and sex

of the patient, number of drugs per prescription, number of drugs prescribed by

generic name, number of prescriptions with injection and/ or antibiotics, number of

drugs prescribed from the essential drugs list, number of drugs prescribed but not

available. In addition, the total number of each drugs prescribed within the study

46

period as well as the frequency of such prescriptions were captured using FORM 3

(Appendix 3).

2.2.2Medication Adherence

Patients’ adherence to psychotherapeutic drugs was assessed using a socio-

demographic questionnaire as well as the Morisky’s Medication Adherence Scale

(MMAS) which was administered to a convenience sample of two hundred (200) out

patients. The questionnaire was divided into two sections. The first section sought to

obtain information about the patients’ demographic characteristics; age, state of

residence, employment status, highest level of education, marital status, having a

caregiver, and history of co-morbidity.

The second section comprised of the eight-item Morisky Medication Adherence

Scale (MMAS-8) which is a reliable37,67 and validated eight-item (Appendix 2);self

reported measure of medication use behavior.68 Each item on the scale measures a

specific medication-taking habit.67 Each question on the MMAS requires only a “yes

or no” answer. The patients were asked about their extent and tendency to forget to

take their medications. They were also asked if they discontinue their medication

upon feeling better or worse. It also included the patients’ beliefs on whether their

treatment plans were seen as an inconvenience or not.

Because of the likelihood of patients giving a false-positive answer, the questions on

the MMAS were appropriately worded in a particular manner to prevent this from

happening. For questions 1-7, answers were awarded scores of 1 for YES and 0 for

NO. For question 8, the answer A attracts the score of 1 while B-E is awarded the

score 0. The scores obtained were summed up to give the overall level of medication

adherence. The MMAS scores have been divided into three levels to classify the

47

level of medication adherence. MMAS scores >2 indicates low adherence, 1 or 2

indicates moderate adherence while MMAS score of 0 shows high medication

adherence.37

The MMAS-8 was well understood by a pilot group of 10 patients who were

excluded from the study. It also had a good test-retest reliability following re-

administration 2 weeks apart.

2.3 DATA ANALYSIS

2.3.1 Analysis of Drug Utilization Data

Extracted information from the prescription sheets were entered into the data

collection form (Form 1) and sorted with the aid of Microsoft excel 2007 and

expressed as means and frequencies. The prescribing indicators were calculated

using the WHO guideline, including average number of drugs per encounter,

percentage of drugs prescribed by generic name or from essential drugs list, and

percentage of encounters during which an antibiotic or injection were prescribed.

The drug use parameters as well as their calculation formula are as shown below, Table 2.0

48

Table 2.0 Drug Utilization Indicators and their formula

The Drug Utilization 90% ( DU 90%) segment reflects the number of drugs that

account for 90% of drug utilization and comprises the drugs whose percentage adds

up to 90%.

The DDD/1000 inhabitants/day was calculated using the ATC classification and

DDD assignment (2010) as given by WHO collaborating center for drug statistics

methodology Oslo, Norway.40

Drug use indicator Calculation

Average number of drugs per encounter Total number of drug products prescribed divided by the total number of encounters surveyed.

Percentage of drugs prescribed by generic name

(The number of drugs prescribed by generic name divided by the total number of drugs prescribed) multiplied by 100

Percentage of encounters with antibiotic (The number of patient encounter during which an antibiotic divided by the total number of encounters surveyed) multiplied by 100

Percentage of encounters with injection prescribed

(The number of patient encounters during which an injection was prescribed divided by the total number of encounters surveyed) multiplied by 100

Percentage of drugs prescribed from essential drugs list

(The total number of products prescribed from the hospital formulary divided by the total number of drugs prescribed) multiplied by 100

Percentage of drugs prescribed but not available

(The number of encounters during which at least a drug was out of stock divided by the total number of encounters) multiplied by 100

49

Formula for DDD/1000 inhabitants/day

⁼ Amount of drugs used in 1 yr(mg) ×1000

DDD(mg)×population × study duration(in days)

2.3.2 Analysis of Adherence Data

Data on patient adherence were collected prospectively from patients and entered

into Form 3.The data collected was stored in an Excel 2007 database and later

imported into Statistical Package for Social Sciences (SPSS) V 17.0 (Chicago IL,

USA) software for analysis. Results were summarized using descriptive statistics

and the chi-square test was used to examine associations between socio-

demographic characteristics and poor medication adherence. Significance was

calculated at p˂0.05.

2.4 ETHICAL APPROVAL

The approval to carry out this study was applied for, and obtained from the Ethical

Committee of the Psychiatric Hospital, Uselu (Appendix 4 and 5).Informed oral

consent was also obtained from all the participants subsequent to the aims and

objectives of the study being described to them.

50

CHAPTER THREE

RESULTS

3.0 DRUG UTILIZATION DATA PRESENTATION

A total number of 5400 prescriptions were used to assess the pattern of drug

utilization in this study. Out of this, 2567 prescriptions were for males (47%) while

2833 prescriptions were for females (53%), Table 3.1.

The age on the prescriptions ranged from 5-94 years. The age distribution as seen in

table 3.1 is as follows: 22 prescriptions were for children, 135 prescriptionsfor

adolescents, 3836 for adults and 823 prescriptions for elderly patients while 584

prescriptions did not have any age information, Table 3.0.

Table 3.0Patient demographics

Patient variables

No of Patients (n) Percentage

TOTAL

GENDER

5400 100

Male 2567 47

Female 2833 53

AGE GROUP (yr)

5-10 (Children)

22 0.41

11-17 (Adolescents)

135 2.50

18-49 (Adults) 3836 71.04

˃ 49 (elderly)

823 15.24

Not indicated 584 10.82

51

The pattern of prescriptionrevealed that the prescribers at the study setting prescribe

approximately 3 drugs per encounter, more than 90 % of the drugs were prescribed

by their generic names andover 30% of the prescriptions had injection prescribed.

The percentage of encounters with antibiotics prescribed was 2.6% while nearly

100% of all the drugs were prescribed from the essential drugs list, Table 3.1.

Table 3.1 Prescribing pattern, based on WHO core drug use indicators108

Prescribing indicator FPHU Reference value

Average number of drugs per encounter 2.88 1.6-1.8

Percentage of drugs prescribed by

generic

94.38% 100%

Percentage of encounter with injection 36.33% 13.4-24.1%

Percentage of encounter with antibiotic 3.2% 20.0-26.8%

Percentage prescribed from EDL 99.2% 100%

FPHU= Federal Psychiatric Hospital, Uselu Benin City, Edo State.

EDL= Essential Drugs List.

52

Out of the 5400 prescriptions encountered, 70.85% had all the drugs prescribed

available in the hospital pharmacy. In 1183 prescriptions, a drug was out of stock;

two drugs were unavailable in 315 encounters while 50 prescriptions and 26

prescriptions had three and four drugs out of stock respectively as seen in table 3.2.

Table 3.2 Drug Availability

No of Drugs Out of

Stock

No of prescriptions encountered Percentage

0 3826 70.85

1 1183 21.91

2 315 5.833

3 50 0.926

4 26 0.481

TOTAL 5400 100

53

The pattern of drug consumption at the outpatient department of the Psychiatric

Hospital, Uselu is shown on Table 3.3. The number of individual tablets or vials of

injectibles used per year as well as their average yearly utilization were expressed in

the table. While the mean consumption shows the average number of tablets or vials

consumed in a year by the sample population (5,400), actual yearly consumption is

the estimated quantity of drugs (expressed in their pack units) consumed in a year by

the whole patient population (108,000) that visit the pharmacy outpatient

department.

For instance, the 439000 tablets of Trifluoperazine consumed yearly at the OPD

pharmacy is arrived at as follows:

Mean yearly consumption for the sample population (5400) = 21944.6 tablets

Then, the consumption for the entire population (108000) = 108000 × 21922.6 = 5400

438892 tablets.

54

Table 3.3 Pattern of Drug consumption at the outpatient pharmacy

S/N DRUG

No of tab/vial consumed in year 1

No of tab/vial consumed in year 2

No of tab/vial consumed in year 3

No of tab/vial consumed in year 4

No of tab/vial consumed in year 5

Mean consumption

Actual yearly consumption*.

1 Trifluoperazine 5mg 25724 26171 22342 19488 15998 21944.6 439 × 1000 2 Benzhexol 5mg 14329 16585 17226 11690 8536 13673.2 273 × 1000 3 Fluphenazinedec 25mg 298 348 301 268 274 297.8 60 × 100 4 Amitriptyline 25mg 24318 24431 26548 26599 18687 24116.6 482 × 1000 5 Chlorpromazine 100mg 18222 17991 19184 14957 11682 16407.2 328 × 1000 6 Haloperidol 5mg 21101 18223 17829 15813 10845 16762.2 335 × 1000 7 Risperidone 2mg 455 461 199 1377 1237 745.8 746 × 20 8 Carbamazepine 200mg 6246 8868 10311 10052 7201 8535.6 171 × 1000 9 Citalopram 20mg 101 346 677 364 317 361 241 × 30 10 Imipramine 25mg 280 1292 1692 1323 671 1051.6 21 × 1000 11 Diazepam 10mg 266 191 135 290 357 247.8 496 × 10 12 Biperiden 5mg 6 8 4 9 10 7.4 30 × 5 13 Fluoxetine 20mg 320 100 345 322 414 300.2 200 × 30 14 Olanzapine 5mg 286 931 212 1704 2023 1031.2 687 × 30 15 Sertraline 50mg 560 324 327 584 424 443.8 296 × 30 16 Flupenthixol 20mg 16 12 19 20 32 19.8 40 × 10 17 Thioridazine 1200mg 658 835 45 196 105 367.8 7 × 1000 18 Paroxetine 20mg 14 2.8 2 × 30 19 Sodium valproate 200mg 1368 1523 1185 3050 2238 1872.8 376 × 100

55

The drugs whose utilization accounted for about 90% of the entire drug use (DU90%) include

Haloperidol, Amitriptyline, Benzhexol, Trifluoperazine, Chlorpromazine and Carbamazepine

(table 3.4). The table also shows the DDD/1000 inhabitants /day for each drug as well as the

actual number of population on the average that consume each drug daily.

Haloperidol was the most utilized drug in the setting with a DDD/ 1000 inhabitants /day of 5

and about 28 patients being placed daily on this drug while the least utilized drug is

paroxetine with DDD/ 1000 inhabitants/ day of 0.001 and about 0.007 patients being on the

drug daily.

56

Table 3.4 Utilization of Psychotropic Drugs expressed as percentages, DDD/1000inhabitants/day and the actual number

of population.

ATC Code Drug

TOTAL NO OF Doses Percentage%

STR (mg)

DDD (mg) DDD/1000/day %POPU

ACTUAL NO OF POPULATION

N06AA09 Amitriptyline * 120583 22.29113442 25 75 4.076339026 0.407633903 22.01223074 N05AB06 Trifluoperazine* 109723 20.28354032 5 20 2.78191047 0.278191047 15.02231654 N05AD01 Haloperidol * 83811 15.49341339 5 8 5.312347876 0.531234788 28.68667853 N05AA01 Chlorpromazine* 82036 15.16528452 100 300 2.773247874 0.277324787 14.97553852 N04AA01 Benzhexol* 68366 12.63823006 5 10 3.466695063 0.346669506 18.72015334 N03AF01 Carbamazepine* 42678 7.889512077 200 1000 0.865644396 0.08656444 4.674479737

93.76111479 N03AG01 Sodium valproate 9364 1.731041546 200 1500 0.126620962 0.012662096 0.683753195 N06AA02 Imipramine 5258 0.972000902 25 100 0.133311022 0.013331102 0.719879518 N05AH03 Olanzapine 5156 0.953145046 5 10 0.26144984 0.026144984 1.411829135 N05AX08 Risperidone 3729 0.68934792 2 5 0.151271754 0.015127175 0.81686747 N06AB06 Sertralline 2219 0.410207304 50 50 0.22504158 0.022504158 1.215224535 N05AC02 Thioridazine 1839 0.339959996 100 300 0.062167863 0.006216786 0.335706462 N06AB04 Citalopram 1805 0.333674711 20 20 0.183055454 0.018305545 0.988499452 N06AB03 Fluoxetine 1501 0.277476865 20 20 0.152225062 0.015222506 0.822015334 N05AB02 Fluphenazinedec 1489 0.275258529 25 1 3.775201817 0.377520182 20.38608981 N05BA01 Diazepam 1239 0.229043195 10 10 0.125654132 0.012565413 0.678532311 N05AF01 Flupentixol 99 0.018301272 20 4 0.050200803 0.00502008 0.271084337 N04AA02 Biperiden 37 0.006839869 5 10 0.001876192 0.000187619 0.010131435 N06AB05 Paroxetine 14 0.002588059 20 20 0.001419821 0.000141982 0.007667032

TOTAL 540946 100

*Drugs that fall within the DU90% segment

57

3.1ADHERENCE DATA PRESENTATION

Characterization of the study subjects: Out of the 200 patients who participated in this study,

the majority were between the ages of 21-30 years and 51% were males, 34% were self

employedand 27.5% were unemployed, more than half of the respondents were single, 61%

had children, close to 50% had secondary education, more than 70% reside in Edo state, 78%

had caregivers at home while 17% of the patients had co morbidity, table 3.5.

58

TABLE 3.5 PATIENT DEMOGRAPHIC CHARACTERISTICS

Patient variables Number of

patients

Percentage

TOTAL 200 100

AGE GROUP

<18 1.0 0.5 18-20 5.0 2.5 21-30 70.0 35.0 31-40 64.0 32.0 41-50 31.0 15.5 51-60 23.0 11.5 >60 6.0 3.0 GENDER Female 98.0 49.0 Male 102.0 51.0 OCCUPATION

Govt. Establishment 10.0 5.0 Private 25.0 12.5 Student 26.0 13.0 Not employed 55.0 27.5 Self employed 68.0 34.0 Others 16.0 8.0 MARITAL STATUS Single 121.0 60.5 Married 60.0 30.0 Separated 10.0 5.0 Widowed 9.0 4.5 HAVE CHILDREN No 123.0 61.5 Yes 77.0 38.5 EDUCATION No formal education 10.0 5.0 Primary 52.0 26.0 Secondary 95.0 47.5 Tertiary 43.0 21.5 STATE OF RESIDENCE Edo 153.0 76.5 Delta 44.0 22.0 Imo 2.0 1.0 Abuja 1.0 0.5 CARE GIVER Yes 156.0 78.0 No 44.0 22.0 CO MOBIDITY Yes 34.0 17.0 No 166.0 83.0

59

Medication treatment compliance behavior: According to the responses from the participants

with regards to the MMAS, 61.5% of them indicated that they took their medication the day

before the interview, whereas 38.5% of the participants did not. Moreover, 64% stated that

they have never cut back nor stopped taking their medication upon feeling that their condition

has worsened or improved. In addition, 52% of the respondents stated that they never forget to

take along their medication when they leave home or travel. Furthermore, the descriptive

statistics part of the table also shows the mean scores of the Morisky’s Medication Adherence

Scale and their standard deviations. From the table, it is observed that the closer the mean

values are to zero for each of the medication taking behavior, the more adherent the patients

are. The Morisky’s adherence scale 7 had the highest percentage adherence (78%, mean value

= 0.22±0.415) while scale 4 had the lowest adherence (52%) with the mean value of

0.48±0.501. Table 3.6

60

TABLE 3.6 DESCRIPTIVE STATISTICS, FREQUENCIES AND PERCENTAGES OF EACH MEDICATION TAKING BEHAVIOR

s/n Morisky’s questions YES NO π S.D

N % N %

1 Do you sometimes forget to take your medication? 118 59 82 41 0.59 ±0.493

2 Over the past two weeks, were there any days when you did not take your medicine? 116 58 84 42 0.58 ±0.495

3 Have you ever cut back or stopped taking your medication without telling your doctor because you felt worse when you took it?

128 64 72 36 0.64 ±0.481

4 When you travel or leave home, do you sometimes forget to bring along your medications? 104 52 96 48 0.52 ±0.501

5 Did you take your medicines yesterday? 123 61.5 77 38.5 0.62 ±0.488

6 When you feel like your illness is under control, do you sometimes stop taking your medicine? 127 63.5 73 36.5 0.64 ±0.483

7 Do you ever feel hassled about sticking to your treatment plan? 156 78 44 22 0.78 ±0.415

8 How often do you have difficulty remembering to take all your medications 106 53 94 47 0.53 ±0.500

Cronbach’s α 6 items = 0.578, items 5 and 8 reverse coded

61

Below, Table 3.7, is the patients’ level of medication adherence. More than half of the

respondents were classified as having low adherence, 36% with moderate adherence

and only 8.5% having high medication adherence level.

TABLE 3.7 LEVEL OF PATIENT ADHERENCE

Level of Adherence Frequency Percentage

Low Adherents 111 55.5

Medium Adherents 72 36.0

High Adherents 17 8.5

Total 200 100

To identify associations between poor adherence and socio-demographic characteristics,

we grouped moderate and good adherents into one and compared with poor adherents.

There were no significant associations with age (p=0.74), gender (p=0.50) employment

status (p=0.09), having children (p=0.97), having a caregiver (p=0.60), marital status

(p=0.87), duration of formal education (p=0.72), or a co-morbidity (p=0.99), Table 3.8

62

Table 3.8: Comparisons of Patients’ Demographic Characteristics with poor medication

adherence

Patient

demographics

Poor Adherence Moderate/Good

Adherence

Statistics

Employment

status Employed Unemployed

96 57

23 24

×2 = 2.845 P = 0.09

Gender Male Female

76 77

26 21

×2 = 0.459 P = 0.50

Has children? No Yes

94 59

29 18

×2 = 0.001 P = 0.974

Age ≤ 40 years ˃ 40 years

108 45

32 15

×2 = 0.107 P = 0.74

Caregiver? No Yes

35 118

9 38

×2 = 0.291 P = 0.60

Co-morbidity? No Yes

127 26

39 8

×2 = 0.01 P = 0.99

Marital status Single Married

92 61

29 18

×2 = 0.037 P = 0.87

Education ≤ 12 years >12 years

121 32

36 11

×2 = 0.132 P = 0.72

63

CHAPTER FOUR

DISCUSSION AND CONCLUSION

4.1 DRUG UTILIZATION

Drug prescription patterns

A prescription provides an insight into aprescriber’s attitude to the disease being treated

and the nature of health care delivery system in the community.106 Using the WHO

prescribing indicators, this study hasprovided a better understanding of theprescribing

practices in the facility beingstudied and has shown areas that needintervention. In the

results shown by this

study, poor quality of pharmacotherapy isreflected. Whereas reference values of 1.6 –

1.8 drugs per encounter were recommendedby the WHO guidelines on rational use of

drugs in the region,108 an average of 2.88 drugs per encounter were prescribed

byclinicians in the facility studied. A closerlook at the pattern reveals that over 50%

ofthe prescriptions had at least 3 drugs. However, highervalues of 3.3 and 3.5 were

reported in studiesdone in some tertiary institutions in Northern Nigeria110,111 while

values of 3.99 and 4.4 had beenreported by workers in Ilorin112 and Benin.106Hogerzeil

and Colleagues had earlierreported much lower figures of 1.3 – 2.2 forBangladesh and

Lebanon respectively.118Polypharmacy,observed in this and other studies across

thedeveloping world, increases the risk of druginteractions and affects

compliance.Literature has shown a linear relationshipbetween the number of drugs

taken andincidence of new hospital admissions peryear due to adverse drug

reactions,inappropriate medication use and mortality.133,134 Other problems associated

with polypharmacy include drug- food interactions and therapeuticduplication errors.

64

Medication adherence canalso be adversely affected leading to poortherapeutic

outcomes.

The WHO expects a 100% prescription by generic name. The high level of generic

prescription observed in this study is a good step in the right direction. Increased

generic prescribing substantially reduces the cost of drugs for the patient and

consequently encourages medication adherence.

Similar higher figures of 75.0 and 99.8 % of generic prescription have been reported

from Bangladesh and Cambodia116 while low values have been reported in Nigeria2,109

and other parts of the world like Ghana,117 Lebanon and Nepal.118A much lower value

of 4.4% was reported in Dubai, in United Arab Emirates.119

This study showed that injections were over prescribedat the Federal Psychiatric

hospital, Benin.The average injection prescribing pattern within thefacility was too high

when comparedto the WHO reference standard108 and the results from previous studies

in Kano(4.0%) and Enugu109 in Nigeria and other countries suchas Tanzania 19%120 and

India 3.9%.121 However the result is lower than the value of 80%obtained by Bosu et

al115 and 71.74% by Babalola et al.30 The high rate of injections use found in this study

however, could be due to the fact that most patients with psychiatric disorders have

been found to be non adherent to their medications,12 therefore depot psychotropic

medications like FluphenazineDecanoate and FlupentixolDecanoate were administered

to these patients to ensure prolonged and sustained antipsychotic cover even in the face

of non adherence to oral medications.

65

The average percentage of encounters with antibiotics found in this study was 3.2%.

This value is lower than the WHO reference point (20.0-26.8%)108 and much lower than

the reports of previous studies in Nigeria- Osun (50.10%)30,Ilorin (45.0 %)112, Benin

City (50.4 %), Kano (67.7 %)110 as well as other countries- Nepal (17.5%)122, Malawi

(34%), Indonesia (43.1%), Bangladesh (25%), and Tanzania (39%).120 This low

antibiotic use is also a pointer to the relative rational prescribing practiced in this

facility and it could also be attributable to the fact that the center is a specialized facility

and therefore, most patients with some other physical ailments that would warrant the

use of antibiotics are appropriately referred to other health care facilities.

Percentage of drugs prescribed from the essential drugList as found by this study was

higher than the average value of84.60% recorded by Melinda et al.123 from his reviewof

previous studies in developing countries.Also, the result is higher than the value from

studies byGuvon et al124(16%) and Hazra et al121(45.70%) but verysimilar to the result

of Babalola et al.30 (94.16), Otoom et al.125(93%) and Bosu et al.115 (97%). Essential

drugslist (EDL) is the list containing drug items essentially usedto treat or manage

common or readily encountereddiseases and/or disorders. Thus the higher

thecompliance with this list, the more rational the drugprescribing pattern. One major

reason for this high percentageof compliance is the availability of the hospital drug

formulary which is adapted from the Essential Drugs List in all the hospital consulting

rooms.

66

Drug Availability

In more than 70% of the prescriptions encountered, all the drugs were available in the

hospital pharmacy. This is, however lower than that reported by IgbiksTamuno from a

study conducted in Kano state, Nigeria where there was about 91.7% drug availability at

the facility studied.109

Drug utilization

The most utilized drugs in the facility studied that fall within the DU90% segment, i.e.

the drugs whose use account for about 90% of all the drugs used in the study site,

include: amitriptyline (22.3%), trifluoperazine (20.3%), haloperidol (15.5%),

chlorpromazine (15.2%), benzhexol (12.6%) and carbamazepine (7.9%). Previous

studies using DU90% method are unavailable; hence, these findings could not be

compared with any previous work.

However, haloperidol was found to be the most prescribed drug because, out of about

60 patients seen in the OPD pharmacy daily, 28 (46.7%) were prescribed haloperidol.

4.2 ADHERENCE

Non-adherence to medication regimens is a seriousproblem. It has many serious effects

on prognosis of theillness and overall effectiveness of health systems.

Nonadherencemay signal that patient and physician differ overgoals and priorities

regarding the treatment and its schedule.126 Non-adherent patients are more severely ill

at thepoint of readmission to hospital, have more frequentreadmissions, are more likely

to be admitted compulsorily,and have longer inpatient stays.127 Increasing the

67

effectivenessof adherence interventions may have a far greater impact onthe health of

the population than any improvement in specificmedical treatments.128

Therefore, information regardingfactors influencing optimal use of medications is

vital.7One of the aims of this study was to determine the levels of adherence among the

outpatients, and also identify patient demographic factors that might impact on

adherence. Assessing medication adherence might lead to a better understanding of

reasonsfor non- adherence in psychiatric patients and lay the groundwork for

interventions aimed at increasing adherence.67

This study finds that over half of patients attending a psychiatry out-patient clinic were

poorly adherent to their medications. The use of a more reliable and validated tool

(MMAS-8) 67 to assess adherence provides strength to the validity of the results. The

lack of an association between socio-demographic and clinical characteristics with poor

adherence may have been limited by the sampling method and the sample size which

limited the study power. This study thus provides more evidence of the magnitude of

medication non-adherence and indicates that multi-disciplinary efforts are needed to

reduce poor adherence to medication rates.

Level of patient adherence to medications

Over half of the patients in this study demonstrated poor adherence. These results do not

differ from previous studies which found high levels (between 50 to 60%) of non-

adherence.129-131In addition, our findings are comparable to that obtained from a study

in South Africa which found 50.6% of patients with moderate adherence and 12.6%

with high adherence level.12 When compared with local studies, the adherence rate in

68

this study is much lower than the over 50% medication adherence identified in a study

by Adelufosi et al136 and about twice lower than that reported by Adewuya et al137 from

a study in southwest Nigeria. The difference in rates may be attributable to the

difference in the psychometric properties of the MMAS-8 which is more reliable

compared to the MMAS-467 which was used in previous studies in Nigeria.

Effects of the patient variables on adherence

The impact of socio-demographic variables such as employment status, having

caregiver, age, gender, occupation, educational status, residential status, marital status

and comobidity on adherence were insignificant. This corroborates the findings in a

study conducted in an outpatient psychiatric setting in Durban, South Africa by Saneleet

al.34 However, a large number of participants (78%) reported that they have caregivers.

Although availability or otherwise of caregivers did not prove to be significantly

associated with adherence in this study, it is important to note that the degree of support

provided by caregivers correlate with a perceived improvement in the prognosis of

mental illnesses.34 Earlier studies have identified social support as one factor that is

consistently associated with outpatient medication adherence.132 The support provided

by caregivers reinforces medication usage, while higher medication usage elicits

supportive behaviors from caregivers and hence leading to what is known as therapeutic

chain of events.132 The lack of a significant relationship between caregiver support and

medication adherence may be attributable to some factors; first the belief systems of the

caregivers may limit their willingness to encourage continuous medication use. Many

lay persons in this environment attribute mental illness to magico-religious factors and

are more willing to encourage the use of recommended treatments by spiritual healers

69

which may conflict with orthodox therapy.39 Secondly, caregivers may not live with the

patients. They may only assist with hospital visits and payments for medicines and thus

do not directly oversee medication adherence. We however did not determine caregiver

relationships which may affect the ability to supervise or encourage medication taking.

For example, a parent may be more persuasive compared to a niece. Perhaps in future

reports this apparent lack of association may be corrected by using an operational

criteria for who a caregiver is.

Forgetfulness is one of the principal factors affecting adherence in the setting studied

because 41% of the respondents reported that they sometimes forgot to take their

medicines, 42% did not take their medicines on some days within the past two weeks

before the interview, 48% of them forget to go along with their medications when the

embark on travel, 38.5% did not take their medicines a day prior to the interview while

almost half of the respondents (47%) reported that they find it difficult remembering to

take their medications. This supports the earlier studies which have related

nonadherence to forgetfulness.34-38Also, 36% of the patients reported to have stopped

taking their medication upon experiencing side effects. This finding is in line with

previous researches which quoted side effects as major barrier to adherence.44-46

4.3 LIMITATIONS OF THE STUDY

Apart from the obvious limitations of a retrospective study, this study has some other

limitations. The prescriptions used in assessing the pattern of prescription were those of

the patients who buy their drugs from the hospital, therefore, the result of this research

70

might not be extrapolated to the prescriptions of such other patients who by choice or

reasons best known to them, do not purchase their drugs in the hospital.

The adherence questionnaire was only served to patients who either understand English

language or whose caregivers do. So the result might not be applicable to those patients

who only speak their native languages.

Again, the study was conducted in one institution; therefore, the result might not apply

to outpatients in other federal Psychiatric Hospitals.

4.4 CONCLUSION

The study found that the prescription pattern at the Federal Psychiatric hospital, Benin

was unsatisfactory, withpolypharmacybeing the major challenge facing clinicians at the

study setting. Haloperidol was the most utilized psychotropic drug.

The level of availability of the key essential drugs in the facility was also not

encouraging with about 30% of the prescribed drugs being sourced outside the hospital.

This study also found that many of the psychiatric outpatients have low adherence level

to their prescribed medications and that medication adherence in the study site was not

influenced by socio-demographic characteristics of the respondents.

71

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