Pharmacophilia and Pharmacophobia: Determinants of Patients’ Attitudes towards Antipsychotic Medication

• Introduction
• Methods
• Subjects
• Drug Attitude Inventory Classification
• Assessment Measures
• Statistical Analysis
• Results
• Sociodemographic and Clinical Characteristics
• Locus of Control, Quality of Life, and Knowledge
• Logistic Regression Analysis
• Illness Concept and Logistic Regression Analysis
• Discussion
• Acknowledgments
• References

Objective: To identify factors that influence attitudes towards psychopharmacological treatment in patients suffering from schizophrenia and schizoaffective psychoses. Methods: Ninety-two participants in an outpatient psychoeducational program, classed as ”pharmacophobic” or ”pharmacophilic” according to the Drug Attitude Inventory scale, were compared with regard to sociodemographic variables, clinical characteristics, subjective deficit syndrome, illness concepts, knowledge, locus of control, and quality of life. Results: The 59 pharmacophilic and the 33 pharmacophobic patients did not differ significantly with regard to most sociodemographic variables, symptoms, or classic personality traits such as locus of control, self-concept, and quality of life. The only differences concerned hospitalization history (P < 0.05) and statements on the actual, subjective experience of desired and undesired effects of medication (P < 0.01). Conclusions: The impact of subjective experiences with drug treatment on attitudes towards medication and compliance needs to be a main focus of interventions targeting attitudes towards pharmacological treatment.

Introduction

Medication compliance is a key issue in the prevention of relapse in schizophrenia. Despite the development of new atypical antipsychotics with better efficacy and fewer side effects, non-adherence is still considerable [8]. A recent review by Zygmunt et al. shows that psychoeducational interventions that do not specifically focus on attitudinal and behavioral change were largely unsuccessful [37]. In a study by Kemp et al. [22], significant improvement in compliance was achieved with the use of compliance therapy - a brief cognitive-behavioral intervention - and was associated with improvement in attitudes and insight. However, this positive finding could not be replicated by O’Donnell et al. [32], who found that compliance therapy was not superior to nonspecific therapy in improving compliance at one year. However, they showed that attitudes to treatment at baseline predicted adherence one year later. Three other recent reviews [10] [19] [21] also underscore the importance of attitudes towards medication as a key factor for compliance.

However, the few studies aimed at identifying factors that influence patients’ attitudes towards psychopharmacological treatment came up with singular findings showing little consistency. A negative attitude towards medication was associated with being employed [14] and having more psychiatric symptoms [6] [9] [11] [14], fewer subjective symptoms of psychosis [35], more side effects [11] [14] [27], lack of insight [6] [27], more time in the hospital [6], and inferior family and social relationships [6] [9]. Most sociodemographic, clinical, and treatment variables under study showed no association with negative attitudes towards medication [6] [11] [14] [15]. Indeed, until now it has been quite unclear to what extent patients’ subjective illness theories, personality traits, and previous experiences with treatments play a role in the development of their attitudes towards medication.

A classification of patients as ”pharmacophobic” [1], i. e. expressing negative attitudes, or ”pharmacophilic” [1], i. e. having a positive attitude, is of essential interest, as these positions correspond to the polarized views regarding the use of psychotropic drugs prevalent in the general public, which shows a strong bias towards pharmacophobic attitudes in Europe and Australia [2] [18] [25] and towards acceptance, but skepticism and unwillingness to use, in the U.S. [7]. Even among professional carers, especially non-medical mental health professionals, negative attitudes towards antipsychotics are common [34].

The present study investigated the role of factors that were previously suggested as having an impact on attitudes towards medication in a group of outpatients typical of the clientele of interventions designed to increase compliance. In addition to the role of sociodemographic and illness-related variables, this analysis sought to determine the possible influences of personality traits such as locus of control and self-concept, patients’ attitude towards their illness, their subjective symptoms, and their subjective quality of life on explaining attitudes towards psychopharmacological treatment comparing patients with pharmacophilic and pharmacophobic attitudes.

Methods

Subjects

The study included 110 outpatients with a diagnosis of schizophrenia or schizoaffective disorder according to ICD-10 criteria [13]. All patients had been referred to a psychoeducational program by their psychiatrists. After complete explanation of the study, written informed consent was obtained.

Drug Attitude Inventory Classification

We grouped patients according to positive or negative scores on the Drug Attitude Inventory (DAI) Scale [15], which assigns scores of + 1 (positive view of medication) and -1 (negative view of medication) to 10 selected items, allowing total scores from -10 to + 10. The DAI [15] was originally designed to group patients into compliers and non-compliers according to their score. While that scale proved to be suitable for classification of patients according to their attitude towards medication as pharmacophilic, i. e., having a positive attitude, and pharmacophobic, i. e. expressing negative attitudes, it is unclear whether this classification directly translates into actual compliant or noncompliant behavior. The item content, factorial structure, validity, and reliability of the DAI are fully described elsewhere [15]. Whereas 92 of the 110 subjects could be clearly categorized as pharmacophobic (n = 33) or as pharmacophilic (n = 59), 18 patients with a score of 0 were not included in the analyses. Scores classified as pharmacophobic range from -10 to -2 scale points with a median of -4.67 (SD = 2.43), and pharmacophilic attitudes are presented by scores ranging from 2 to 8 scale points with a median of 4.17 (SD = 2.04).

Assessment Measures

The following self-rating questionnaires were administered:

1. The Subjective Deficit Syndrome Scale [17], a valid and reliable instrument that consists of 19 items that measure subjective complaints perceived by the patient on a five-point scale (1, strongly disagree to 5, strongly agree).

2. The Illness Concept Scale, the KK-scale [26], for schizophrenic patients, a valid and reliable instrument with 29 items for assessing patients’ illness-related attitudes in seven dimensions: confidence in their medication (scores from 0 to 20), confidence in their physician (scores from 0 to 16), negative expectations towards their medication (scores from 0 to 20), attribution of illness to chance (scores from 0 to 20), susceptibility to illness and to relapse (scores from 0 to12), attribution of guilt (scores from 0 to 12), and fear of side effects of medication (scores from 0 to 16). The higher the score, the higher the expression of the respective dimension.

3. The FKK, a questionnaire of Competence and Control [23], a valid and reliable scale with 32 items for assessing the locus of control and self-concept on four subscales with total scores ranging from 8 to 32: ”positive self-concept,” ”internality,” ”powerful others,” and ”chance/”

4. The KKG, a German-modified version of the Multidimensional Health Locus of Control Scale [28], a valid and reliable instrument with 21 items consisting of the subscales ”internal,” ”external-p” (powerful others), and ”external-c” (chance) with total scores ranging from 7 to 28.

5. The quality of life index (QLI) [30], a concise instrument for comprehensive and culture-informed assessment of health-related quality of life with 10 items. The QLI provides an assessment of the following 10 dimensions of quality of life: physical well-being, psychological well-being, self-care and independent function, occupational functioning, interpersonal relations, social support, satisfactory environment, personal fulfillment, spiritual fulfillment, and overall quality of life. Each item is rated on a 10-point scale (1, very poor to 10, excellent quality of life).

6. The knowledge questionnaire from the Munich Psychosis Information Project [4], an instrument for assessing knowledge about symptoms, etiology, and treatment strategies including medication in patients with schizophrenia. Total scores of correct answers range from 0 to 56.

Sociodemographic and clinical variables including current age, level of education, occupational status, living situation, social network, age at onset of illness, age at first admission, number of previous hospitalizations, PANSS score [20], and current psychopharmacological and psychosocial treatment conditions were assessed in a routine clinical interview by a psychiatrist.

Statistical Analysis

All statistical analyses were performed using SPSS 10. Chi-square tests, t-tests, and Mann-Whitney U-tests were calculated for univariate analyses. A multiple logistic regression model was used to check the results found in the univariate analyses. Furthermore, we performed a multiple logistic regression analysis to calculate adjusted odds ratios (OR) and 95 % confidence limits for single variables of the illness concept scale. P-values <0.05 were considered statistically significant.

Results

Sociodemographic and Clinical Characteristics

The sociodemographic and clinical characteristics of the two groups are listed in

Table [1]. The only significant differences were that pharmacophobic persons were older at onset of illness and that pharmacophilic subjects were found significantly more often in the group having experienced 2-5 prior hospitalizations, as distinct from those with fewer and those with more hospitalizations. All other variables-sex, education, working and living situation, social network, age, age at first admission, diagnosis, PANSS (positive, negative, general), Subjective Deficit Syndrome Scale, treatment conditions, including type and number of prescribed medications-showed no statistically significant differences. Also, no significant differences were found in the analysis of the diagnostic subtypes (schizophrenia: 22 paranoid, 1 disorganized, 2 catatonic, 2 undifferentiated, 13 residual; schizoaffective disorder: 5 manic, 3 depressive, 11 mixed). Nearly all persons of both groups (89.1 %) reported taking prescribed antipsychotic medication. For 80.5 % this meant a regimen of only one antipsychotic drug. More than half of both groups (64.6 %) used atypical antipsychotic medication, and the majority (69.6 %) also used tranquilizers and/or antidepressants.

Locus of Control, Quality of Life, and Knowledge

No significant differences were found between the groups on the questionnaire of Competence and Control (FKK) and the locus of control scale (KKG). There was also no significant difference between the groups on the quality of life index. Even on the knowledge questionnaire, pharmacophobic persons did not differ significantly from pharmacophilic ones with regard to correct answers (see Table [2]).

Logistic Regression Analysis

To adjust for possible confounding variables, relevant variables were included in a logistic regression model. Independent variables included in the regression model were, in the order of their P-values in the univariate analyses, sex, education, age at onset of illness, number of previous hospitalizations, and knowledge. The significant difference of number of previous hospitalizations between the groups was confirmed by the multiple logistic regression model, while the significant difference of age at onset of illness was not (Table [3]).

Illness Concept and Logistic Regression Analysis

As expected, the two groups differed on those subscales of the Illness Concept Scale that dealt with attitudes towards medication. Pharmacophobic persons had significantly less confidence in their medication and their physician, more negative expectations toward medication, and more fear of medication side effects (Table [2]).

To identify the items most important for the significant differences found in the Illness Concept Subscales, a logistic regression analysis was performed. In a first step, each item was separately placed into a logistic regression model along with the confounders. In a second step, all items showing a statistically significant odds ratio were combined in a single model. Following this procedure, only two items were significant (P < 0.01). In a final step, these two items and confounders were included in one model, and the respective odds ratios are shown in Table [4]. Confounders included sex, age at first diagnosis, and educational status. Subjects who agreed with the statement ”medication impairs me in every day life” and who disagreed with the statement ”medication is of great help in mental illness” were at a significantly higher risk to be classified as pharmacophobic.

Discussion

Pharmacophobic and pharmacophilic attitudes were not indicative of differences for most variables under study between the two groups. In contrast to previous studies, we failed to find differences concerning employment status [14], positive or negative symptoms [6] [9] [11] [14], subjective symptoms [35], and social relationships [6] [9]. Our failure to find a better attitude towards psychopharmacological treatments among persons treated with second-generation antipsychotics is consistent with previous findings [6] [11] [14] [27], but contrasts with the results of the recent review of Lambert et al. [24] and may be due to the small sample size and the variety of treatment conditions. Patients from our study group frequently received more than one antipsychotic, and they often took one or more additional adjunctive pharmacological agents, a common practice in psychiatry [5] [12] [29] [33]. The two groups did not differ in their knowledge about schizophrenia, classic personality traits such as locus of control and self-concept, or their subjective quality of life-variables not studied previously. An attempt at polarizing the two groups more by using the extreme quartiles concerning the grouping into individuals with pharmacophilic and pharmacophobic attitudes (M = 6.43; SD = 0.84 and M = -6; SD = 1.85) did not significantly change the overall picture: apart from the expected significant changes in illness concept, the few differences found (the extreme pharmacophilic group had more knowledge about the illness, a better quality of life, and comprised more men) lost significance after correction for multiple testing (Bonferroni).

The only pointers identified (significant differences between both groups) are derived from the previous experience of patients during the course of illness and with regard to hospital admissions. The significant differences found in the Illness Concept Scale were expected because both the subscales of the Illness Concept Scale, which reached statistical significance, and the Drug Attitude Inventory assessed attitudes towards psychotropic drugs. However, two statements from the Illness Concept Scale had a high predictive value for belonging to the pharmacophobic group. Persons who agreed that medication disturbs their every day lives and disagreed that medication is of great help often qualify as pharmacophobic. The relation of these subjective experiences to adverse drug reactions as objectively assessed remains unclear, because actual und past medication side effects were not recorded. The finding that persons who do not experience medication as helpful and who feel impaired by medication have a negative attitude towards medication or are noncompliant agrees with the results of previous studies [16] [36].

Another interesting result concerns hospital admissions. Pharmacophilic patients were found more often in the group having experienced 2-5 prior hospitalizations, whereas patients with more or fewer admissions tended towards pharmacophobia. This puzzling result of an analysis of a rather arbitrary variable concerning the number of prior hospital admissions still warrants discussion. Previous studies reported no correlation of the number of prior hospitalizations with attitudes towards medication [15] [36]. One explanation for our result might be found when adopting the view that patients originally come from a situation where they clearly are part of the general public and thus most likely share the common public attitude of pharmacophobia (before the onset of illness). Subsequently, some patients will change their attitude, having benefited from psychiatric treatment and medication. In some instances, patients may have experienced relapse because they stopped taking their medication. This type of experience may cause people to modify their initial dislike of psychotropic drugs. However, patients with more than five hospitalizations, probably having experienced relapse despite compliance with medication, might once more change their attitude towards psychopharmacological treatment in the sense that their confidence in medication decreases.

In contrast to a previous finding [3], we found in a univariate analysis that pharmacophobic patients are older at the onset of illness. People who are older at the onset of illness may have had more time to adopt the negative public attitude concerning the use of psychotropic drugs. However, the significant difference of age at onset could not be confirmed by multivariate analysis because of the high correlation of later age of onset and female sex.

The present study has several limitations. As in all outpatient studies on this population, the sample consists of essentially stable patients who were motivated to participate in a research project on a topic of psychoeducational intervention. Therefore, although patients had been found in need of psychoeducation, patients with negative attitudes might be underrepresented. However, patients with positive attitudes also might be underrepresented. Study participants were stable but had a considerable number of residual symptoms as reflected by a PANSS total score in the mid-70 s; therefore, they might have lost their positive belief in antipsychotics at least to some degree. A further limitation may be the size of the study, which may explain a possible underestimate of differences between the two groups under study. However, when two samples of n = 33 and n = 59 are compared by t-test with a two-sided significance level of 0.05, mean differences between the groups on the order of around 60 % of standard deviation would be detected with a power of 80 %.

Under the assumption that a substantial number of patients simply start out sharing the skepticism of the general public towards psychopharmacological treatment [2] [7] [18] [25], we hypothesize that some patients will change their opinion during the course of their illness while others will not. Our results, which indicate that patients’ attitudes towards medication is influenced only by factors relating to personal experience, provide motivation for increasing efforts to expediently find the individually helpful medication at the right dosage for each person in clinical practice. Furthermore, in order to facilitate controlled experiments with personal experience, we should be prepared to agree with patients’ demands for changes in medication; this will foster a trustful patient-physician relationship and enable a process of learning from experience, expertise, and shared decision-making [31].

Acknowledgments

We thank the patients who served as participants in this project. We thank Thomas Zidek, M.D., and Monika Himmelbauer, M.A., of the Medical University of Vienna for assisting with statistical analyses.

References

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Ingrid Sibitz, M.D.

Department of Psychiatry

Medical University of Vienna

Währinger Gürtel 18-20

A-1090 Vienna

Phone: 0043/1/40400-3546

Fax: 0043/1/40400-3605

Email: Ingrid.Sibitz@meduniwien.ac.at

References

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• 10 Fenton W S, Blyler C R, Heinssen R K. Determinants of medication compliance in schizophrenia: empirical and clinical findings.  Schizophr Bull. 1997;  23 637-651
  Search in Google Scholar
• 11 Gervin M, Browne S, Garavan J, Roe M, Larkin C, O'Callaghan E. Dysphoric subjective response to neuroleptics in schizophrenia: relationship to extrapyramidal side effects and symptomatology.  Eur Psychiatry. 1999;  14 405-409
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  Search in Google Scholar
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  PubMedSearch in Google Scholar
• 15 Hogan T P, Awad A G, Eastwood R. A self-report scale predictive of drug compliance in schizophrenia: reliability and discriminative ability.  Psychol Med. 1983;  13 177-183
  PubMedSearch in Google Scholar
• 16 Holzinger A, Löffler W, Müller P, Priebe S, Angermeyer M C. Subjective illness theory and antipsychotic medication compliance by patients with schizophrenia.  J Nerv Ment Dis. 2002;  190 597-603
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  PubMedSearch in Google Scholar
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  CrossrefPubMedSearch in Google Scholar
• 19 Kampman O, Lehtinen K. Compliance in psychoses.  Acta Psychiatr Scand. 1999;  100 167-175
  PubMedSearch in Google Scholar
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Ingrid Sibitz, M.D.

Department of Psychiatry

Medical University of Vienna

Währinger Gürtel 18-20

A-1090 Vienna

Phone: 0043/1/40400-3546

Fax: 0043/1/40400-3605

Email: Ingrid.Sibitz@meduniwien.ac.at