Fewer symptoms vs. more side-effects in schizophrenia? Opposing pathways between antipsychotic medication compliance and quality of life

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Abstract

Background

Non-compliance with medication often has long-term detrimental effects in patients with schizophrenia. However, when patients are compliant, it is not certain whether they experience short-term improved quality of life. By simultaneously reducing symptoms and increasing side-effects, compliance with antipsychotics may have opposing effects on a patient's perceived quality of life.

Aim

This study aimed to identify any clinical–empirical evidence for two pathways between compliance and quality of life.

Method

To evaluate various pathways between compliance (Service Engagement Scale plus a one-item rating), psychotic symptoms (Positive and Negative Syndromes Scale), adverse medication effects (Subjective Wellbeing under Neuroleptics scale), and quality of life (EQ-5D), we used Structural Equation Modeling on cross-sectional data of 114 patients with a psychotic disorder.

Results

Compliance was not directly related to quality of life (r = 0.004). The best-fitting model (χ2 = 1.08; df = 1) indicated that high compliance was associated with fewer psychotic symptoms (β =  0.23) and more adverse medication effects (β = 0.22). Symptoms (β =  0.17) and adverse medication effects (β =  0.48) were both related to lower quality of life.

Discussion

Our results suggest that compliance with antipsychotics has two opposing pathways towards quality of life, albeit indirect ones. While compliance was associated with less severe psychotic symptoms, and was thus related to higher quality of life, it was also associated with more adverse medication effects, and was thus related to lower quality of life. However, due to our study design, we cannot draw firm conclusions on causality. Two possible clinical implications of the results for compliance and interventions are discussed.

Introduction

Many patients with either a somatic or a psychiatric disorder do not comply with medication. Based on a review, Cramer and Rosenheck (1998) estimate that, on average, patients who have been prescribed somatic medicine use only 76% of the pills. This percentage is lower in the case of antipsychotics, where only 58% of the prescribed medication is estimated to be actually taken. Keith and Kane (2003) aptly conclude their review by observing that while compliance with medication is difficult for everyone—for example in the field of diabetes, high blood pressure, asthma, or birth control—it is particularly difficult for people with schizophrenia. Four studies have shown that 50% to 75% of patients on antipsychotic medication become non-compliant after one to two years of treatment (Bebbington, 1995, Thomas, 2007, Weiden et al., 1996, Weiden et al., 1991). Obviously, non-compliance makes it difficult to achieve the effects intended for treatment. When a patient stops using antipsychotics, the risk of relapse and admission or readmission increases three to five-fold (Dixon and Lehman, 1995, Fenton et al., 1997, Robinson et al., 2002, Ucok et al., 2006, Weiden et al., 2004). It should be mentioned, however, that in some cases non-compliance may follow clinical deterioration, which can be due to resistance in therapy, making causal attributions on the relationship between non-compliance and relapse difficult. In the same way, the risk of suicide may be 3.75 times higher in non-compliant patients with schizophrenia than it is in those who are compliant (Hawton et al., 2005), though here it is important to realise that depression increases the risk of non-compliance (Elbogan et al., 2005) as well as of suicide.

Although the long-term consequences of non-compliance are often detrimental to patients with schizophrenia, it is less obvious whether those who are compliant experience any short-term improvement in their quality of life. While three studies have found that people suffering from schizophrenia experienced substantially lower quality of life than healthy subjects (Carlsson et al., 2002, Reine et al., 2003, Zissi et al., 1998), few studies have investigated how experienced quality of life was affected by compliance with antipsychotics. One study reported an association between compliance and quality of life in first-episode patients (Coldham et al., 2002). Another initially found a small positive association that however was not borne out by subsequent statistical modelling (Puschner et al., 2006).

Arguably, by reducing symptoms on the one hand and increasing side-effects on the other, compliance with medication involves two mechanisms, each affecting a patient's perceived quality of life in a different direction. Although Puschner et al. (2006) did indeed find that better compliance and higher perceived quality of life were mediated by a reduction in psychopathology, they did not find that better compliance and lower quality of life were mediated by an increase in medication side-effects. This may be because they used the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS, Day et al., 1995)—a good self-report scale of side-effects that nonetheless does not make it possible to quantify their overall burden on a patient. It has been found in other studies, however, that side-effects of antipsychotics are associated with a reduced perceived quality of life (Angermeyer and Matschinger, 2000, Yen et al., 2008), and that they are sometimes a reason for discontinuing medication (Lambert et al., 2004, Robinson et al., 2002).

The objective of this study was to test the hypothesis that medication compliance has two opposing and indirect associations with a patient's perceived quality of life: (1) that, by reducing psychotic symptoms, better compliance is associated with increased quality of life; and (2) that, by increasing adverse medication effects, better compliance is associated with poorer quality of life.

Section snippets

Study population

Participants were respondents in a multi-centre randomized controlled trial that took place in the Dutch city of Rotterdam and investigates the effects of Treatment Adherence Therapy (TAT). TAT is a tailored intervention in which, depending on a patient's individual reasons or causes of non-compliance, four different intervention modules can be applied, for example behavioral interventions or an adapted form of motivational interviewing. For a more detailed description, see Staring et al. (2006)

Patient characteristics

A total of 195 patients were asked to participate in the randomized controlled trial described above. Seventy-nine of them declined to participate. Of the remainder, two were too disorganized in thought and speech to be able to complete the questionnaires. The remaining 114 completed the baseline assessments. Lifetime diagnoses: 79 of these patients (69%) met the criteria of schizophrenia (60 paranoid type, 11 disorganized type, 7 catatonic type, and 1 undifferentiated type), and 35 (31%) met

Discussion of the results

Our results suggest that compliance with antipsychotics in patients with a psychotic disorder involves two different and indirect pathways towards quality of life. While compliance seems to reduce psychotic symptoms—which may increase quality of life—compliance also seems to increase adverse medication effects—which may reduce quality of life. This finding is largely in line with an earlier study which found not only (1) that compliance with antipsychotics had no direct effect on quality of

Role of funding source

Funding for this study was provided by the Dutch Ministry of Health, Welfare, and Sports (ZonMw, research grant number 100-002-017). ZonMw played no further role in the study design or in the collection, analysis and interpretation of data; the writing of the report; or the decision to submit the paper for publication.

Contributors

Authors Mulder, Gaag, and Staring designed the study and wrote the protocol. Staring managed the literature. Authors Duivenvoorden and Staring undertook the statistical analyses. De Haan advised on the study design. Staring wrote the first draft of the manuscript. All authors contributed to revisions and have approved the final manuscript.

Conflict of interest

None.

Acknowledgements

We would like to thank all the participating patients, caregivers, and administrative, medical and paramedical staff at Erasmus University Medical Centre, Parnassia Bavo Group, Delta Psychiatric Centre, ‘De Grote Rivieren’ Community Psychiatric Health Centre, and ‘Riagg Rijnmond’ Community Psychiatric Health Centre.

References (46)

  • ClaassenD. et al.

    Money for medication: financial incentives to improve medication adherence in assertive outreach

    Psychiatri. Bull.

    (2007)
  • ColdhamE.L. et al.

    Medication adherence of individuals with a first episode of psychosis

    Acta Psychiatr. Scand.

    (2002)
  • CramerJ.S. et al.

    Compliance with medication regimes for mental and physical disorders

    Psychiatr. Serv.

    (1998)
  • DayJ.C. et al.

    A self-rating scale for measuring neuroleptic side-effects. Validation in a group of schizophrenic patients

    Br. J. Psychiatry

    (1995)
  • De HaanL. et al.

    Psychometric properties of the Subjective Wellbeing Under Neuroleptics scale and the Subjective Deficit Syndrome scale

    Psychopharmacology

    (2002)
  • DixonL.B. et al.

    Family interventions for schizophrenia

    Schizophr. Bull.

    (1995)
  • ElboganE.B. et al.

    Medication non-adherence and substance abuse in psychotic disorders

    J. of Nerv. Ment. Dis.

    (2005)
  • FentonW.S. et al.

    Determinants of medication compliance in schizophrenia: empirical and clinical findings

    Schizophr. Bull.

    (1997)
  • HawtonK. et al.

    Schizophrenia and suicide: systematic review of risk factors

    Br. J. Psychiatry

    (2005)
  • JöreskogK.G.

    Testing structural equation models

  • KarowA. et al.

    Association of subjective well-being, symptoms, and side-effects with compliance after 12 months of treatment in schizophrenia

    J. Clin. Psychiatry

    (2007)
  • KayS.R. et al.

    The positive and negative syndrome scale (PANSS) for schizophrenia

    Schizophr. Bull.

    (1987)
  • KeithS.J. et al.

    Partial compliance and patient consequences in schizophrenia: our patients can do better

    J. Clin. Psychiatry

    (2003)
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