Summary

Drugs 25: 63-76 (1983)

0012-6667/83/0100-0063/$07.00/0'" ADIS Press Australasia Pty Ltd (Inc. NSW). All rights reserved.

The Problem of Non-compliance withDrug Therapy

Larry Evans and Michael SpelmanDepartments of Psychiatry, University of Queensland andPrincess Alexandra Hospital, Brisbane

Non-compliance with drug treatment is widespread. When patients are given medicationby their doctors. nearly halfdo not take the drug or do not take it as prescribed. and mostwill stop the treatment as soon as they are feeling better.

A major problem in identifying the non-compliant patient is the unreliability of manyofthe measures used for assessing compliance. There are few social and demographic char­acteristics associated with non-compliance. The type of disease. also. generally has littleinfluence on the level of compliance. Psychological factors such as the patients ' levels ofanxiety. motivation to recover. attitudes towards their illness. the drug and the doctor. aswell as the attitudes and beliefs ofsignificant others in their environment do influence thepatients' levels ofcompliance.

Many of the factors that are related to non-compliance with drug regimens are withinthe control ofhealth care professionals. Contrary to the beliefs ofmany doctors, studies donot support the view that drug non-compliance is a deviant form of behaviour influencedby patient characteristics.

Keep watch also on the fault of patients which oftenmake them lie about the taking of things pre­scribed.

Hippocrates

This observation by Hippocrates that patientsor people often do not take things as prescribed isone that has been made many times since the daysof the ancient Greeks. It has been noted that peo­ple not only deviate from the advice given themabout medication regimens, but they also behave

in the same way about advice given them by phy­sicians regarding diets and patterns of lifestyle. Ascompliance affects the outcome of treatment, in atleast some diseases, it is desirable that non-com­pliance be reduced as much as possible.

Compliance is defined as the extent to which aperson's behaviour (in terms of taking medica­tions, following diets, or executing lifestylechanges)coincides with medical or health advice (Haynes,1979). Blackwell (1976) comments that the term

Non-compliance with Drug Therapy

has been in use only since 1975. Prior to this, thedescriptive term 'patient drop-out' was used.Blackwellhimselfpreferred the term 'adherence' tobe used, feeling this to be without the coercive con­notations of compliance. However, compliance andnon-compliance are still the terms most widely usedand in this review we will continue with this prac­tice.

The increasing numbers of effective drugs whichhave been made available during the past few dec­ades have caused issues of compliance and non­compliance to become much more important. Thisis reflected by the increase in the number of pub­lications on the subject of compliance. Blackwell(1976) has claimed that , as with other areas ofmedical knowledge, information on compliance isroughly doubling every 5 years. He notes that be­tween 1956 and 1960 there were 12 publicationson the topic; from 1961 to 1965 there were 45; from1966to 1970there were 79; and from 1970 to 1975there were 133 articles. Blackwell also advanced asother major reasons for the increased interest incompliance: (1) the enhanced awareness of patients'rights; (2) a decline in professional paternalism; (3)a slowing down in the pace of drug discovery lead­ing to a closer look at those drugs already available;and (4) an increased interest in the benefits ofpreventative help, such as long term drug main­tenance therapy. He suggests that the situationwhere short term side effects of some drugs appearto be worse than the remote consequences of thedisease causes patients to be less compliant, thusbringing the whole issue to attention. Finally, hestates that the increasing availability of measuresto assess drug levels in the body, thereby identi­fying more clearly whether a patient is compliantor not, has created further interest in the topic, bymaking the assessment of compliance more accu­rate.

Becker and Maiman (1975) have gone so far asto suggest that as non-compliance is so widespread,its occurrence, resulting in poor medical outcome,may account for a considerable proportion of thegeneral dissatisfaction with the delivery of health

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care. Although it has generally been agreed that anincrease in compliance with treatment is desirable,Sackett (1976) has issued a word of caution:

'The decision to apply strategies deliberately de­signed to change compliance behaviour must meetat least three pre-conditions: namely, the diagnosismust be correct; therapy must do more good thanharm; patients must be informed willing partnersin any manoeuvre to increase compliance '.

In this article we will review the issues con­cerned with non-compliance with drug treatment.Problems associated with the assessment of com­pliance and the size of the problem are discussedalong with those factors which influence non­compliance.

1. Problems in IdentifyingNon-compliance

A major difficulty in interpreting the data oncompliance is the different design methods be­tween the various studies and different criteria foridentifying non-compliance. Investigating theproblem in a variety of disease entities and the ex­istence of other methodological and epidemiolog­ical differencesmakes a comparison between studiesdifficult to interpret. Another difficulty is that themore attention that is paid to the non-compl iantpatient , the more likely it is that the patient willcomply with the treatment regimen. There is alsogood evidence to show that , in the initial stages ofinvestigation of non-compliance, more specificmethods of checkingproduce higher figures for non­compliance. Staff observation produces higher fig­ures than those obtained from patient's admiss ionof non-compliance; pill counts provide higher non­compliance figuresthan staff observation; and urineand blood checks produce even higher figures(Mulgirigama et al., 1977).

Blackwell (1976) has categorised non-compli­ance with drug treatment into 5 types:a) Errors of omissionb) Taking of medicine for the wrong reasons

Non-compliance with Drug Therapy

c) Errors in dosaged) Mistakes in timinge) Taking additional medication not prescribed by

the physician. Most of the literature on non­compliance with drug treatment has been con­fined to studies of errors of omission.

1.1 Methods of Assessing Non-compliance

A basic differentiation between direct and in­direct methods of assessing compliance and non­compliance can be made: the direct methods arethose by which the drug can be identified in thepatient; the indirect methods include those wherethere is an assessment, either by the patient himselfor some other individual, as to whether the patientis likely to have taken the medication (Gordis ,1979). Direct methods generally give higher figuresfor non-compliance than indirect methods.

1.1.1 Direct Methods

Blood Level MonitoringIt is now possible to estimate the blood levels

of many drugs and their metabolites, whereas inthe past this has been difficult. The concentrationof a drug or its metabolites in the blood will oftengive some indication of the actual dose being takenby the patient, particularly when there is a clearrelationship between dose and steady-state bloodlevel (Biggs et al., 1976; Sheiner et al., 1974; Wittset al., 1977). Complying with treatment to achieveand maintain this level is even more importantwhen the drug level is specifically related to thetherapeutic effect.

When it is too difficult to identify a substancein the blood, a compound that can be more easilyidentified is added to the therapeutic agent and actsas a marker, e.g. the use of sodium bromide (Rothet al., 1970).

Measurement of Urinary ExcretionIt has been possible to develop techniques to

identify certain drugs which are excreted in the

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urine (Chaves, 1959; Gilroy, 1952; Kent, 1966;Markowitz, 1970). The phenothiazines and tri­cyclic antidepressants are 2 groups which can beidentified in the urine (Ballinger et al., 1975; For­rest et al., 1961 ; Nelson et al., 1975). The excretedmetabolites of some drugs can also be identifiedand used to measure compliance (Wilcox et al.,1965).

A marker compound has also been used by at­taching it to the therapeutic agent and so enablingthe urinary excretion of the drug to be measured.An example of this procedure is the use ofriboflavine as a marker (Hobby and Deuschle,1959).

Other MethodsAn attempt has been made to utilise the stools

of psychiatric patients by giving an opaque bariumsulphate tracer detectable by x-rays in the faeces(Blackwell, 1976).

A 'breath test' has also been developed to iden­tify drugs or drug metabolites in the expired air ofpatients taking disulfiram (Paulson et al., 1977).

1.1.2 Indirect Methods

Asking the Patient and/or Other PeoplePatients can be asked verbally or by question­

naire whether they have been complying with thetreatment (Gabriele and Marble, 1949; Johnson,1973; Lipman et al., 1965). Similarly, relatives(Johnson, 1973) or nursing staff (Ballinger et al.,1975) can be asked to what extent the patient hasbeen complying with the treatment. The doctor whoprescribed the medication can also be asked to as­sess how well the patient is complying with thetreatment regimen.

Pill CountsWith this method the patient is asked to return

a medication container at regular intervals. Theamount of medication not used is counted andprovides a basis for an assessment of compliance(Johnson, 1973,1974;Park and Lipman, 1964). One

Non-compliance with Drug Therapy

technique is to give the patient more medicationthan required for the period under study and tocount the tablets left in the bottle when returned.

Outcome of Therapy and Presence ofSide EffectsThe outcome of therapy is an obvious basis for

assessing whether the patient has complied withtreatment (Franch et al., 1957; Glennon, 1966).

With certain drugs, side effects occur consist­ently when the patient is on a therapeutic dosage.Assessment of these side effects may give an in­dication as to whether the patient is complying withthe treatment programme or not.

1.2 Limitations of Methods of AssessingNon-compliance

It has been possible to compare the accuracy ofvarious methods of assessing compliance by usinga number of differing techniques in the same groupof patients (Davis, 1966; Mulgirigama et aI., 1977).It has been found that the more direct the tech­nique and the more specific its use, the more likelyit is that the observer will identify non-compliance;for example, estimation of drug blood levels willbe more revealing than asking patients whether theyare complying with treatment (Mulgirigama et al.,1977). With more specific techniques it is possiblethat patients will realise that their compliance isbeing checked and so become more compliant(Blackwell, 1976).

1.2.1 Limitations ofDirect Methods

Blood Level and Urine Excretion TestsThese studies are inconvenient and can be ex­

pensive. Some patients object to having bloodspecimens taken, regarding this as unnecessary andintrusive . Moreover, the actual process of carryingout these specificchecks, if done regularly, may wellgive a false indication of the level of complianceby temporarily increasing it. The value of assessing

66

compliance in this way depends greatly on the re­liability of the method by which the drug is iden­tified or quantified in the body fluids. Where themethod is not sensitive, both false positive andnegative results may occur. The reported differ­ences in metabolism of drugs by various individ­uals may well be a further factor limiting theusefulness of direct estimations as a measure ofcompliance (Biggs et al., 1976).

When such direct methods of assessing compli­ance have been used, the degree of non-compliancehas always exceeded that expected. Mulgirigamaand colleagues (1977) found that compliance as­sessed by direct questioning and pill count did notalways coincide with plasma concentrations of thedrug, and it was found that patients who failed tobring back their remaining tablets nearly alwaysachieved lower than expected plasma concentra­tions of the drugs. When patients with peptic ulcertook liquid antacids with a bromide marker, therewas only a 'moderate' correlation between bottlecounts and their matched bromide levels (Roth etal., 1970). Witts et aI., (1977) found when they es­timated plasma levels that some patients were givenor took wrong medications only at certain times,while others took the wrong medication through­out the whole of the study. Ballinger et al. (1974,1975)found in 2 studies where the urine was testedthat 6.4% and 7.9%, respectively, of patients hadnot taken any of the drug tested despite close nurs­ing supervision . In another study, Porter (1969)found that 3 of 19 patients taking imipramine hadnegative urine assays, but complete pill counts .

1.2.2 Limitations of Indirect Methods

Asking the Patient and RelativesWhile a proportion of patients who are non­

compliant may be identified by direct questioning,many will not. Studies comparing patient reportswith other methods, such as pill counts and urineand blood tests, indicate that a substantial numberof patients who say they are taking their medica­tion are not telling the truth (Park and Lipman,

Non-compl iance with Drug Therapy

1964;Preston and Miller, 1964; Wilcox et al., 1965).Asking relatives is also unreliable as they often donot know the degree of compliance of the patient- they have either not been told or they have notbeen told the truth (Francis et aI., 1969; Gordis etaI., 1969). In addition, relatives might themselvesbe non-compliant in terms ofadministration of thedrug or assessment of compliance in the patient .This probably relates to their own attitudes to tak­ing medication. This method is also dependent onthe relative's willingness to report non-compliance.We consider that this method is unreliable; not onlydoes it have its own variables but these may occurin addition to the non-compliance of the patient.

Asking Nurses and Nurse AssessmentThe unreliability of this method relates to the

difficulties nurses have in assessing whether patientshave actually consumed the given medication. Ifpatients are given medication parenterally by anurse, the nurse 's assessment is more reliable thanif the patient is given medication in tablet form.There is also some difference between the situationwhere a nurse gives a patient a tablet and watcheshim taking this medication, and where the nursegives the patient medication to take away foradministration at .their own discretion. Ballingerand colleagues (1975) have shown that nurse ob­servation identifies 1.7% non-compliance whereasurine tests showed 7.9% of the same patients to benon-compliant. In this study, drug administrationrecord sheets showed that only 50% of the ob­served drug errors were recorded.

Physician AssessmentAssessment by physicians is also thought to be

of little value, as physicians have a tendency tooverestimate the degree of compliance in theirpatients. It has been shown by Davis (1966) thatthe more senior the physician, the more likely heis to overestimate compliance in his patients.However, other studies have shown that even jun­ior physicians have no more than a.50% chance ofidentifying whether their patients are complying

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with the prescribed medication (Caron and Roth,1968; Gordis , 1979; Mushlin and Appel, 1977).

Pill CountsThis method of assessment is open to consid­

erable doubt as a measure of compliance, but it ismore reliable than interview. Park and Lipman(1964) showed that while 15% of their patients re­ported their non-compliance, a pill count identi­fied a 51% deviation. It has been noted that somepatients will dispose of medication that they havenot taken to give the impression that they havebeen complying with treatment (Mulgirigama et al.,1977). A more reliable method of assessing com­pliance is to give the patient a greater number oftablets than they require and to assess whether thenumber left tallies with the overall treatment reg­imen . There have been reports ofother people tak­ing the patient's medication, leading to anoverestimation of compliance (Gordis, 1979).

Outcome of TherapySome studies have shown that, with certain types

of drug treatment, the outcome gives some indi­cation ofcompliance (Markowitz, 1970). With somedrugs this indication is quite clear; for example,patients who are on ant iconvulsants who are notcomplying with their medication will be more likelyto have fits than those who are complying (Kutt etaI., 1966). For many types of treatment, however,this approach is not sufficiently sensitive, becauseeven when patients comply, this does not neces­sarily ensure a satisfactory outcome (Lowenthal etaI., 1976). Gordis (1976) suggests that there are somany other factors which are important in the out­come of treatment that this is generally thought tobe a poor measure of compliance. Salkind (1976)has mentioned the importance of life events in in­fluencing the outcome of treatment.

Presence of Side EffectsThe limitation of this method is that patients

are often unreliable in reporting side effects, asshawn by the occurrence of many side effects when

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patients are taking placebo in double-blind con­trolled trials. Some drugs have regularly occurringpredictable side effects and some indication ofcompliance might be obtained by assessing the oc­currence and degree of these (Sackett, 1976).

2. The Extent ofNon-compliance

2.1 Methodological Considerations

While there have been numerous studies whichhave attempted to quantify the degree of non-com­pliance in various groups of patients, the results ofmany of these studies are open to serious doubtsregarding theis validity because of methodologicalproblems. Sackett and Snow (1979) reviewed 537original studies and found that less than 40 of thesestudies satisfied their strict methodological re­quirements for the following factors:a) Study designb) Sample, selection and specificationc) Description of illnessd) Description of therapeutic regimene) Completeness of definitions of compliancef) Adequacy of the measures of assessing non­

compliance.

2.2 Reported Estimates of Non-compliancein Various Reviews

Davis (1966) reported an overall figure for non­compliance with medication instructions of 30 to35%, with the figures for the various studies re­viewed ranging from 15 to 93%. Stewart and Cluff(1972) reviewed a number of studies ofcomplianceand concluded that the percentage ofpatients mak­ing errors in self-administration of prescribed drugsranged between 29 and 59%. In addition, 4 to 35%were misusing their medication in such a manneras to pose a serious threat to their health, while thepercentage of patients failing to take their medi­cation as directed ranged from 20 to 82%. Simi-

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larly, Blackwell (1973) noted that 25 to 50% ofoutpatients do not comply with medication in­structions. A review of 25 studies of non-compli­ance found that in 22 of these the rate of non­compliance was 30%or more (Stimson, 1974). Thisreview also pointed out that the criteria for non­compliance varied greatly, with some studies beingmuch less exacting than others in the criteria whichthey accepted.

Ley et al. (1976) in their review of a number ofstudies found a mean figure for non-compliancewith health advice of 44%: for patients on para­aminosalicylicacid and other antituberculosis drugsthe figure was 27.5%; for antibiotics, 48.7%; forpsychotropic drugs, 38.6%; for other drugs 47.7%;for those on diets, 49.4%; and for other advice, childcare and antenatal exercises etc., 54.6%. In a re­view of 14 studies of non-compliance, Evans (1980)found a mean of about 40%(range: 24-72%). It wasclear that these figures were dependent on a num­ber of factors, some of these relating to differencesin methodology, but others related to differencesin patient population, the illness studied and othermatters relating to the treatment.

In the 40 studies that they finally considered ,Sackett and Snow (1979) looked at compliance andnon-compliance in relation to both the treatmentand the prevention of illness. They reviewed bothshort and long term medication and found a varietyof methods of assessing compliance, which wereutilised in a number of different illnesses. Theynoted that there was some variation in the figuresfor non-compliance with treatment and that thiswas influenced by a number of factors. One con­sistent finding was that the figures for non-com­pliance were high, but were influenced by factorssuch as the time-span of treatment and whether themedication was for prophylactic or curative rea­sons. In 2 studies of short term medication as apreventative health measure, non-compliance wasat a level of 36 and 40%, respectively (Burnip etal., 1976; Hogue, 1976). A study of the long termprophylactic use of penicillin showed a non-com­pliance rate of 66% (Gordis, 1969). This figure de-

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pends on how long the patient has already beentaking the drug when the study is undertaken. Onestudy showed non-compliance of only 6% after 1year but 66% after 3 years (Hedstrand and Aberg,1976). In studies where the treatment was curative,non-compliance ranged from 23% with short termmedication (Donabedian and Rosenfeld, 1964) to32-59% for long term treatment of conditions asvaried as tuberculosis, leprosy and psychiatric dis­orders (Davis, 1966; Hertroijs, 1974; Schwartz etal., 1962).

3. Factors Associated withNon-compliance

Many factors other than the method of assess­ing compliance have been considered in trying todistinguish the compliant from the non-compliantpatient. In this section these are grouped intopatient characteristics and factors associated withthe treatment process (i.e. characteristics associ­ated with the illness and the doctor/patient rela­tionship) .

3.1 Patient Characteristics

A review of a number of studies of non­compliance by Davis (1968) noted that the non­compliant patient is more likely to be older, fe­male, of lower socioeconomic status, and have alower level ofeducation than a patient who is com­pliant. Age also appeared to be a factor in 2 otherstudies: Bergman and Werner (1963) found thatolder children were more likely to receive medi­cation prescribed for them than younger children,while Krucko (1978) showed that patients affectedby an illness before their twenty-fifth year attendedcheck-ups less regularly than those who first be­came ill when they were older. However, in an ex­tensive review of those factors relating to the patientwhich have an association with non-compliance,Haynes (1976) noted that while some studies

69

showed an association between non-compliance andlower socioeconomic status , poor education andolder age, the majority showed no such association.There was also no association found between non­compliance and sex or religion.

Psychological and environmental factors can in­fluence compliance. For example, Havens (1968)commented that where an illness is serving apositive function for the patient, he may resist ef­forts to be cured. The hospital may be the mostpleasant place the patient has lived in, giving himno motivation to get better. This is similar to theobservations of Richards (1964) who found that'stayers' in hospital who were non-compliant withtreatment did not have more positive attitudes tohospital , but they had more negative attitudes tohome and particularly to their relatives; they didnot have particularly negative attitudes towardsmedication, but refused it because of their negativeattitude towards authority. Raskin (1961) noted thatpatients who were overtly non-compliant withmedication were much more hostile and used thedrug issue as a convenient focal point for their hos­tile and aggressive impulses. There is also someevidence to suggest that patients living with theirfamilies are more likely to take medication thanthose living alone (Goldberg et al., 1977; Parkes etal., 1962; Renton et al., 1963; Wilcox et al., 1965).However , Stimson (1974) came to the conclusionthat while there have been studies that have iden­tified certain characteristics of patients who do notfollow doctor's orders, few significant differenceshave been found between defaulters and compliers.

3.2 Treatment Factors

3.2.1 Duration of TreatmentAlthough there has been some disagreement be­

tween investigators as to the relationship betweenlength of treatment and compliance (Haynes, 1976),the stage of treatment at which the study is com­menced appears to be a crucial issue. It would ap­pear that the longer the person has already been

Non-compliance with Drug Therapy

on treatment, if they still attend a doctor, the morelikely they are to comply with that treatment Thus,when patients are studied from the time that theystart treatment the overall non-compliance rate willbe higher than for those who enter a study afterthey have been on treatment for some time.

Johnson (1973) found that of73 patients treatedfor depression by general practitioners, 16%stoppedthe drug within 1 week, 41% within 2 weeks, 59%within 3 weeks, and 68% within 4 weeks. 26% ofthose who stopped treatment thought this was un­necessary because they felt improved, 21% becausetheir supply of tablets had finished and they hadnot obtained or been-given further prescriptions,and 7%because of side effects. In nearly every casemedication was stopped without the doctor know­ing. In a later study, Johnson (1974) found that65% of patients attending hospital as out-patientsfor treatment of depression were not taking theirmedication regularly after I month. Furthermore,in a study of 54 patients being treated for tuber­culosis, the majority of treatment failures occurredwithin the first few months (Crocco et aI., 1976).

3.2.2 Acceptability ofand Attitudes toTreatmentCompliance is influenced by how acceptable the

patient finds the treatment and also by the atti­tudes to health matters held by the patient andothers with whom he comes in contact. Surpris­ingly, it was shown in 1 study that those who arecoerced into receiving treatment for alcoholism aremore likely to comply than those who are volun­tary patients (Rosenberg, 1974). This study alsosuggested that compliance was better when therewas some incentive to comply other than health;for example, the incentive suggested for compli­ance with alcohol programmes is loss of employ­ment. Rosenberg also noted the occurrence ofdrug­induced side effects as a factor in the patient's fail­ure to continue with treatment. Many other au­thors have also noted that side effects are a reasonfor non-compliance (Hogarty and Goldberg, 1973;Johnson, 1973, 1974; Nies, 1975; Porter, 1969;

70

Rickels and Downing, 1966; Van Putten, 1974,1978).

The attitude of patients to the treatment thatthey receive greatly influences their motivation tocomply with a medication regimen. Sackett (1976)hasreviewedvarious aspectsofwhat he terms 'socio­behavioural features' in relation to compliance. Heconsiders that patients who perceive their illnessas serious and believe in the efficacy of treatmentwill be more likely to comply. This was not relatedsignificantly to knowledge of treatment, intelli­gence or general education. Foo Lin et al. (1979)found that patients who had insight into their ill­ness, who perceived benefits of medication and alsoperceived a relationship between the two are morelikely to take medication than those who did nothave this insight and did not perceive the benefits.In their study, 45% of patients with insight com­plied with their regimen while only 17% withoutinsight complied. Of those who perceived somebenefit from their treatment, 36% complied as op­posed to 15% who did not perceive benefits. Theeffect of insight on compliance has also been notedby others (Van Putten et aI., 1976).

There are also cultural attitudes which influencecompliance including attitudes towards medica­tion and the whole concept of illness (Blackwell,1976). Fear of dependence on drugs is a frequentlygiven explanation for ceasing medication prema­turely (Johnson, 1974; Stimson, 1974). Somepatients do not comply with medication becausethey feel guilty taking any drugs, while others fearbecoming 'immune' to the treatment.

Non-compliance occurs for many other reasonsrelated to the individual's acceptance of the treat­ment and attitude towards it. One study (Segal etaI., 1976) found that a methadone maintenanceprogramme was not acceptable to addicts becausethe design of the programme prevented them tak­ing the methadone home to sell. Davis (1968) con­sidered that the attitudes of persons close to thepatient can also influence the patient's compliance.Taking medication may seem to some to be astigma of incurable illness and non-compliance may

Non-compliance with Drug Therapy

be a means of avoiding this reminder (Prien andCaffey, 1977).

3.2.3 The Drug RegimenThe method of administration can influence

compliance. There have been a number of studieswhich show that parenteral administration pro­vides better compliance in schizophrenic and otherpatients, and hence better therapeutic response thanoral medication (CoIcher and Bass, 1972;Crawfordand Forrest, 1974; Feinstein et al., 1959; Johnsonand Freeman, 1972; Mohler et al., 1956).

Some non-compliance is due to failure of mem­ory and lack of understanding of the treatment reg­imen on the part of the patient (Ley and Spelman,1967; Ley et al., 1976; Parkin et al., 1976), and ithas been shown that patients are more likely tocomply with less complex regimens (Davis, 1966;Parkin et al., 1976). Multiple medication and fre­quent dosage regimens have been shown to be as­sociated with poor compliance (Mazzulo, 1972).Haynes (1979) has shown from a review of the lit­erature that increasing the number of treatmentsprescribed decreases compliance , but commentsthat the correlation between the number of dailydoses and compliance is equivocal. Burgoyne (1976)found, rather surprisingly, that changes in treat­ment do not appear to affect compliance.

The high cost of medication can also be a factorin preventing compliance (Brand et al., 1977).

3.2.4 The Treatment SettingThere is good evidence to show that patients are

more compliant when attending a clinic for treat­ment, and with the subsequent treatment givenwhen they are not kept on a waiting list for a longtime (Finnerty et al., 1973; Rockart and Hofman,1969; Rosenberg and Raynes, 1973). Careful andfrequent supervision of patients is also more likelyto be associated with better compliance and thereis evidence showing that inpatient compliance isbetter than day patient compliance , which itself isbetter than outpatient compliance. (Hare and Wil­cox 1967; Johnson, 1977; Sheiner et al., 1974).

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However, the regularity of attendance for check­ups tends to diminish with increasing numbers ofhospital admissions (Krucko, 1978).

3.3 The Nature and Severity of the Illness

While many studies have looked at a variety offactors that may be associated with non-compli­ance in a variety of different disease states, only afew studies have considered the disease state itselfas a factor in non-compliance. The whole issue ofdisease state and .compliance is a complex one asthere are so many variables associated with dis­eases that might also influence compliance. For ex­ample, the illness itself might influence the patient'sability to comply or their awareness of the neces­sity for compliance, as has been mentioned earlier.Patients with insight into their illness do complybetter than those without. One only needs to con­sider the hypomanic patient who becomes moremanic and grandiose and no longer entertains theidea that treatment for his manic depressive dis­order is needed.

A major difficultyin comparing compliance ratesbetween different disease states is the wide rangefor non-compliance shown by studies conductedeven in the one disease state. Evans (1980) foundthat in 7 studies undertaken on antituberculosisdrugs, the range for non-compliance was between30 and 72%, and the range for 7 studies of psy­chiatric disorders was between 24 and 68%.

3.3.1 DiagnosisHaynes (1979) has reviewed the literature crit­

ically and has commented that there are few ob­vious associations between disease features andcompliance. He claims that the only associationbetween diagnosis and non-compliance is with apsychiatric diagnosis and that compliance is par­ticularly low amongst schizophrenic patients, es­peciallythose with paranoid features. Other authorshave commented that grandiosity occurring in aschizophrenic illness or in hypomania is also likely

Non-compliance with Drug Therapy

to be associated with poor compliance (Benson,1975; Prien and Caffey, 1977; Schou, 1970; VanPutten , 1974, 1975). However, Johnson (1977) inhis review of compliance in schizophrenics failedto show an unduly high non-compliance rate inthese patients compared with the other groups ofpatients. Moreover, he found that the non-com­pliance rate for schizophrenics was reduced by theuse of depot' injection preparations of antipsy­chotic drugs from 48% to 34%, and that this ratefell even further to 15% when a special clinic su­pervised by a trained psychiatric nurse was set upto cater specifically for these patients. However, thisassociation between non-compliance and schizo­phrenia or mania is the only evidence of a specificassociation between non-compliance and a psychi­atric diagnosis.

3.3.2 Severity of IllnessWhile it would seem reasonable to expect more

severely ill patients to be more compliant withtreatment than less severely ill patients, Davis(1966) certainly did not find this to be so. On thecontrary, he found that those with severe ailmentswere more likely to have good intentions and tobe more likely to fail than those with less severedisorders. However, he noted that it is difficult tobe sure whether the non-compliance affects the se­verity of the condition or vice versa. Davis alsofound that the greater the effect of the illness onperforming daily activities, the less likely the patientwas to follow the doctor's advice, and that thosewith psychological or social disabilities were lesslikely to falter. Of those who were disabled phys­ically, 90% indicated that they were willing to fol­low doctor 's orders, but only 44% actually did so.Other studies have also found that patients whoare more ill are less likely to adhere to treatmentregimens (Bonnar et al., 1969; Brand et al., 1977;Lipman et aI., 1965; Renton et al., 1963).

Becker and Maiman (1975) suggest that low lev­els of anxiety associated with specific illnesses arenot sufficiently motivating to produce compliance,while very high levels of anxiety, including fear,

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are so inhibit ing that they might produce non-com­pliance. They also point out that this variable re­fers to the patient's subjective perceptions ratherthan some medical or objective estimate of howserious the illness may be. The one association be­tween illness and non-compliance that is consist­ently reported is that when patients get better froman illness they are less likely to comply with treat­ment (Heinzelman, 1962;Johnson , 1973; Prien andCaffey, 1977; Rickels et aI., 1968).

3.4 The Doctor/Patient Relationship

Doctors tend to blame personality characteris­tics of the patient for non-compliance - older doc­tors being more inclined to do this than youngerones (Davis, 1966).The situation is more complexthan this, however. The relationship between doc­tor and patient is a major determinant in compli­ance with drug regimens and continuing attendancefor treatment. Although the first visit to the doctorwould seem to be important in establishing a sat­isfactory doctor/patient relationship, it does notseem to play a major part in determining latercompliance (Davis, 1968). Regular contact with thedoctor improves compliance (Rosenberg, 1974),which further improves if the relationship is goodwith effective communication between the two.

There is evidence that improvement in doctor/patient communication is a factor in increasingcompliance, particularly where this is related to in­creasing understanding and satisfaction on the partof the patient, since many health-related messagesare not understood by the patients (Ley, 1980).Furthermore, between 37 and 54%of what the doc­tor tells the patient is forgotten (Ley, 1979; Ley andSpelman, 1967). Compliance with a medicationregimen can be improved by providing the patientwith more understandable information (Ley et aI.,1975; 1976) and also supplying written informa­tion, providing this leads to an increase in know­ledge (Morris and Halperin, 1979).

The attitude of the doctor towards the patient

Non-compliance with Drug Therapy

will also influence compliance. A study of patientsdischarging themselves from hospital found thatthese discharges occurred only when certain staffmembers were on duty (Rosenberg and Raynes,1973). With some patients, a good relationship willensure attendance, but not compliance. These arepatients who have positive feelings towards thedoctor but feel unimproved and dislike their med­ication (Rickels et aI., 1968). However, other stud­ies have shown that a good therapeutic alliance witha doctor who is enthusiastic about treatment andits outcome will ensure better compliance (Benson,1975; Uhlenhuth et aI., 1966). Enthusiasm and ac­tivity on the part of the doctor is important; a pas­sive doctor who accepts authoritative behaviourfrom a patient is likely to promote non-compliance(Davis, 1968).

4. Conclusions

Non-compliance with drug treatment is wide­spread. While there is a wide variation in figuresfor non-compliance between studies, there is gen­eral agreement that when patients are given med­ication by a doctor , nearly half will either not takethe drug or not take it as prescribed and most willstop their treatment as soon as they are feeling bet­ter.

There is a tendency amongst doctors to blamethe individual chacteristics of the patient for non­compliance. However, the whole issue is a muchmore complex one with few social and demo­graphic characteristics correlating with complianceand non-compliance. It does seem likely that olderpeople have more difficulties in following medi­cation regimens and this is possibly related to thefact that they have difficulty with memory. Iso­lated people and those living alone are less likelyto comply with treatment, particularly if they aresuffering from mental illness, and patients fromlower socioeconomic groups do not comply withtreatment as well as those from higher socioeco­nomic groups. However, these are all factors which

73

only have a slight bearing on overall complianceand probably only contribute a minor proportionof those large numbers of patients who are non­compliant with treatment.

Psychological and emotional factors play agreater role in determining compliance than de­mographic factors. A level ofanxiety either too lowor too great may well be related to non-compli­ance. When patients have some vested interest inretaining their symptoms, they will resist takingmedication, particularly if this is likely to makethem better. They will comply more readily withtreatment if they do not have ideological viewsagainst drug treatment and if they are not undulyhostile towards the treatment and the doctor pre-­scribing it. If they believe that drugs are going toproduce some improvement in their condition theywill also be more likely to comply. The attitudesof relatives and friends also have an influence oncompliance, particularly in children but also inadults.

The type of disease being treated does not greatlyinfluence whether there is compliance or not. Anumber of authors have noted, however, thatschizophrenic and hypomanic patients who areshowing paranoid delusions or who are grandiosein their attitudes do not comply readily with treat­ment. This is an example of how the disease itselfcan interfere with an individual's ability to followa treatment programme.

The method by which the treatment is given tothe patient can also influence the individual's ad­herence to a treatment regimen. For example, whenpatients are observed taking their medication theyare more likely to take it than when they are notobserved. Intramuscular injections are much morelikely to ensure compliance than oral medication.In addition, the venue of the treatment programmewill influence compliance, patients treated in hos­pital being much more likely to comply with theirtreatment than those treated as outpatients.

From the many studies that have investigatedthe subject of non-compliance it is clear that whiledoctors view this as some form ofdeviant and hos-

Non-compliance with Drug Therapy

tile behaviour on the part of patients who havesome character defect, the phenomenon is so wide­spread that it might well be considered normal be­haviour. Most of the factors which influencecompliance and non-compliance can be controlledto some extent by the doctor rather than the patient.Even when these are taken into account and meas­ures are taken to improve compliance, non-com­pliance is still a frequent event, which is more likelyto occur as the patient gets better.

Acknowledgements

The authors wish to thank Mrs Eileen Harris, MrsKay Muldoon and Mrs Jean Spelman for their help inpreparing this review.

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Author's address: Dr Larry Evans, Department of Psychiatry,University of Queensland, Princess Alexandra Hospital, IpswichRoad, Woolloongabba, Queensland (Austral ia).